bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Roles of Serotonin (5-HT) and 5-HT-Receptors in Health and Disease
Authors: Neumann Joachim , Hofmann Britt , Dhein Stefan , Gergs Ulrich
Published: March 2023

Serotonin acts solely via 5-HT4-receptors to control human cardiac contractile function. The effects of serotonin via 5-HT4-receptors lead to positive inotropic and chronotropic effects, as well as arrhythmias, in the human heart. In addition, 5-HT4-receptors may play a role in sepsis, ischaemia, and reperfusion. These presumptive effects of 5-HT4-receptors are the focus of the present review. We also discuss the formation and inactivation of serotonin in the body, namely, in the heart. We identify cardiovascular diseases where serotonin might play a causative or additional role. We address the mechanisms which 5-HT4-receptors can use for cardiac signal transduction and their possible roles in cardiac diseases. We define areas where further research in this regard should be directed in the future, and identify animal models that might be generated to this end. Finally, we discuss in what regard 5-HT4-receptor agonists or antagonists might be useful drugs that could enter clinical practice. Serotonin has been the target of many studies for decades; thus, we found it timely to summarise our current knowledge here.
Peroxisomes Are Highly Abundant and Heterogeneous in Human Parotid Glands
Authors: Watermann Christoph , Meyer Malin Tordis , Wagner Steffen , Wittekindt Claus , Klussmann Jens Peter , Erguen Sueleyman , Baumgart-Vogt Eveline , Karnati Srikanth
Published: March 2023

The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland’s striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.
Molecular Dynamics Assessment of Mechanical Properties of the Thin Filaments in Cardiac Muscle
Authors: Koubassova Natalia A. , Tsaturyan Andrey K.
Published: March 2023

Contraction of cardiac muscle is regulated by Ca2+ ions via regulatory proteins, troponin (Tn), and tropomyosin (Tpm) associated with the thin (actin) filaments in myocardial sarcomeres. The binding of Ca2+ to a Tn subunit causes mechanical and structural changes in the multiprotein regulatory complex. Recent cryo-electron microscopy (cryo-EM) models of the complex allow one to study the dynamic and mechanical properties of the complex using molecular dynamics (MD). Here we describe two refined models of the thin filament in the calcium-free state that include protein fragments unresolved by cryo-EM and reconstructed using structure prediction software. The parameters of the actin helix and the bending, longitudinal, and torsional stiffness of the filaments estimated from the MD simulations performed with these models were close to those found experimentally. However, problems revealed from the MD simulation suggest that the models require further refinement by improving the protein–protein interaction in some regions of the complex. The use of relatively long refined models of the regulatory complex of the thin filament allows one to perform MD simulation of the molecular mechanism of Ca2+ regulation of contraction without additional constraints and study the effects of cardiomyopathy-associated mutation of the thin filament proteins of cardiac muscle.
IGFBP-6 Network in Chronic Inflammatory Airway Diseases and Lung Tumor Progression
Authors: Venuto Santina , Coda Anna Rita Daniela , González-Pérez Ruperto , Laselva Onofrio , Tolomeo Doron , Storlazzi Clelia Tiziana , Liso Arcangelo , Conese Massimo
Published: March 2023

The lung is an accomplished organ for gas exchanges and directly faces the external environment, consequently exposing its large epithelial surface. It is also the putative determinant organ for inducing potent immune responses, holding both innate and adaptive immune cells. The maintenance of lung homeostasis requires a crucial balance between inflammation and anti-inflammation factors, and perturbations of this stability are frequently associated with progressive and fatal respiratory diseases. Several data demonstrate the involvement of the insulin-like growth factor (IGF) system and their binding proteins (IGFBPs) in pulmonary growth, as they are specifically expressed in different lung compartments. As we will discuss extensively in the text, IGFs and IGFBPs are implicated in normal pulmonary development but also in the pathogenesis of various airway diseases and lung tumors. Among the known IGFBPs, IGFBP-6 shows an emerging role as a mediator of airway inflammation and tumor-suppressing activity in different lung tumors. In this review, we assess the current state of IGFBP-6’s multiple roles in respiratory diseases, focusing on its function in the inflammation and fibrosis in respiratory tissues, together with its role in controlling different types of lung cancer.
A Particular Focus on the Prevalence of α- and β-Thalassemia in Western Sicilian Population from Trapani Province in the COVID-19 Era
Authors: Daidone Rossella , Carollo Antonella , Perricone Maria Patrizia , Messina Renato , Balistreri Carmela Rita
Published: March 2023

Thalassemia is a Mendelian inherited blood disease caused by α- and β-globin gene mutations, known as one of the major health problems of Mediterranean populations. Here, we examined the distribution of α- and β-globin gene defects in the Trapani province population. A total of 2,401 individuals from Trapani province were enrolled from January 2007 to December 2021, and routine methodologies were used for detecting the α- and β-globin genic variants. Appropriate analysis was also performed. Eight mutations in the α globin gene showed the highest frequency in the sample studied; three of these genetic variants represented the 94% of the total α-thalassemia mutations observed, including the −α3.7 deletion (76%), and the tripling of the α gene (12%) and of the α2 point mutation IVS1-5nt (6%). For the β-globin gene, 12 mutations were detected, six of which constituted 83.4% of the total number of β-thalassemia defects observed, including codon β039 (38%), IVS1.6 T > C (15.6%), IVS1.110 G > A (11.8%), IVS1.1 G > A (11%), IVS2.745 C > G (4%), and IVS2.1 G > A (3%). However, the comparison of these frequencies with those detected in the population of other Sicilian provinces did not demonstrate significant differences, but it contrarily revealed a similitude. The data presented in this retrospective study help provide a picture of the prevalence of defects on the α and β-globin genes in the province of Trapani. The identification of mutations in globin genes in a population is required for carrier screening and for an accurate prenatal diagnosis. It is important and necessary to continue promoting public awareness campaigns and screening programs.
Prevention of Ventriculostomy Related Infection: Effectiveness of Impregnated Biomaterial
Authors: Diop Sylvain , Roujansky Ariane , Kallel Hatem , Mounier Roman
Published: March 2023

External ventricular drain(EVD) exposes the patient to infectious complications which are associated with significant morbidity and economic burden. Biomaterials impregnated with various antimicrobial agents have been developed to decrease the rate of bacterial colonization and subsequent infection. While promising, antibiotics and silver-impregnated EVD showed conflicting clinical results. The aim of the present review is to discuss the challenges associated with the development of antimicrobial EVD catheters and their effectiveness from the bench to the bedside.
Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant
Authors: Bordi Licia , Sberna Giuseppe , Lalle Eleonora , Fabeni Lavinia , Mazzotta Valentina , Lanini Simone , Corpolongo Angela , Garbuglia Anna Rosa , Nicastri Emanuele , Girardi Enrico , Vaia Francesco , Antinori Andrea , Maggi Fabrizio
Published: March 2023

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.
Exosomes Derived from Adipose Stem Cells Enhance Bone Fracture Healing via the Activation of the Wnt3a/β-Catenin Signaling Pathway in Rats with Type 2 Diabetes Mellitus
Authors: Zhang Dong , Xiao Weidong , Liu Changjiang , Wang Zheng , Liu Yuhang , Yu Yifeng , Jian Chao , Yu Aixi
Published: March 2023

Nonunion and delayed union are common complications of diabetes mellitus that pose a serious health threat to people. There are many approaches that have been used to improve bone fracture healing. Recently, exosomes have been regarded as promising medical biomaterials for improving fracture healing. However, whether exosomes derived from adipose stem cells can promote bone fracture healing in diabetes mellitus remains unclear. In this study, adipose stem cells (ASCs) and exosomes derived from adipose stem cells (ASCs-exos) are isolated and identified. Additionally, we evaluate the in vitro and in vivo effects of ASCs-exos on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone repair and the regeneration in a rat model of nonunion via Western blotting, immunofluorescence assay, ALP staining, alizarin red staining, radiographic examination and histological analysis. Compared with controls, ASCs-exos promoted BMSC osteogenic differentiation. Additionally, the results of Western blotting, radiographic examination and histological analysis show that ASCs-exos improve the ability for fracture repair in the rat model of nonunion bone fracture healing. Moreover, our results further proved that ASCs-exos play a role in activating the Wnt3a/β-catenin signaling pathway, which facilitates the osteogenic differentiation of BMSCs. All these results show that ASCs-exos enhance the osteogenic potential of BMSCs by activating the Wnt/β-catenin signaling pathway, and also facilitate the ability for bone repair and regeneration in vivo, which provides a novel direction for fracture nonunion in diabetes mellitus treatment.
Molecular Detection and Identification of Plant-Associated Lactiplantibacillus plantarum
Authors: Skotniczny Magdalena , Satora Paweł
Published: March 2023

Lactiplantibacillus plantarum is a lactic acid bacterium often isolated from a wide variety of niches. Its ubiquity can be explained by a large, flexible genome that helps it adapt to different habitats. The consequence of this is great strain diversity, which may make their identification difficult. Accordingly, this review provides an overview of molecular techniques, both culture-dependent, and culture-independent, currently used to detect and identify L. plantarum. Some of the techniques described can also be applied to the analysis of other lactic acid bacteria.
Epigenetic Signatures in Arterial Hypertension: Focus on the Microvasculature
Authors: Mengozzi Alessandro , Costantino Sarah , Mongelli Alessia , Mohammed Shafeeq A. , Gorica Era , Delfine Valentina , Masi Stefano , Virdis Agostino , Ruschitzka Frank , Paneni Francesco
Published: March 2023

Systemic arterial hypertension (AH) is a multifaceted disease characterized by accelerated vascular aging and high cardiometabolic morbidity and mortality. Despite extensive work in the field, the pathogenesis of AH is still incompletely understood, and its treatment remains challenging. Recent evidence has shown a deep involvement of epigenetic signals in the regulation of transcriptional programs underpinning maladaptive vascular remodeling, sympathetic activation and cardiometabolic alterations, all factors predisposing to AH. After occurring, these epigenetic changes have a long-lasting effect on gene dysregulation and do not seem to be reversible upon intensive treatment or the control of cardiovascular risk factors. Among the factors involved in arterial hypertension, microvascular dysfunction plays a central role. This review will focus on the emerging role of epigenetic changes in hypertensive-related microvascular disease, including the different cell types and tissues (endothelial cells, vascular smooth muscle cells and perivascular adipose tissue) as well as the involvement of mechanical/hemodynamic factors, namely, shear stress.
Amorphous System of Hesperetin and Piperine—Improvement of Apparent Solubility, Permeability, and Biological Activities
Authors: Wdowiak Kamil , Miklaszewski Andrzej , Pietrzak Robert , Cielecka-Piontek Judyta
Published: March 2023

The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many compounds when co-administered. The aim of this paper was to prepare and characterize the amorphous dispersions of hesperetin and piperine, which could help to improve solubility and boost the bioavailability of both plant-origin active compounds. The amorphous systems were successfully obtained by means of ball milling, as confirmed by XRPD and DSC studies. What’s more, the FT-IR-ATR study was used to investigate the presence of intermolecular interactions between the systems’ components. Amorphization enhanced the dissolution rate as a supersaturation state was reached, as well as improving the apparent solubility of both compounds by 245-fold and 183-fold, respectively, for hesperetin and piperine. In the in vitro permeability studies simulating gastrointestinal tract and blood-brain barrier permeabilities, these increased by 775-fold and 257-fold for hesperetin, whereas they were 68-fold and 66-fold for piperine in the GIT and BBB PAMPA models, respectively. Enhanced solubility had an advantageous impact on antioxidant as well as anti-butyrylcholinesterase activities—the best system inhibited 90.62 ± 0.58% of DPPH radicals and 87.57 ± 1.02% butyrylcholinesterase activity. To sum up, amorphization considerably improved the dissolution rate, apparent solubility, permeability, and biological activities of hesperetin and piperine.
Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System
Authors: Seifert Joshua , Chen Yingfu , Schöning Wenzel , Mai Knut , Tacke Frank , Spranger Joachim , Köhrle Josef , Wirth Eva Katrin
Published: March 2023

The energy homeostasis of the organism is orchestrated by a complex interplay of energy substrate shuttling, breakdown, storage, and distribution. Many of these processes are interconnected via the liver. Thyroid hormones (TH) are well known to provide signals for the regulation of energy homeostasis through direct gene regulation via their nuclear receptors acting as transcription factors. In this comprehensive review, we summarize the effects of nutritional intervention like fasting and diets on the TH system. In parallel, we detail direct effects of TH in liver metabolic pathways with regards to glucose, lipid, and cholesterol metabolism. This overview on hepatic effects of TH provides the basis for understanding the complex regulatory network and its translational potential with regards to currently discussed treatment options of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) involving TH mimetics.
Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State
Authors: Sinenko Sergey A. , Kuzmin Andrey A. , Skvortsova Elena V. , Ponomartsev Sergey V. , Efimova Evgeniya V. , Bader Michael , Alenina Natalia , Tomilin Alexey N.
Published: March 2023

The monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has important functions both in the neural system and during embryonic development in mammals. In this study, we set out to investigate whether and how endogenous serotonin affects reprogramming to pluripotency. As serotonin is synthesized from tryptophan by the rate limiting enzymes tryptophan hydroxylase-1 and -2 (TPH1 and TPH2), we have assessed the reprogramming of TPH1- and/or TPH2-deficient mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs). The reprogramming of the double mutant MEFs showed a dramatic increase in the efficiency of iPSC generation. In contrast, ectopic expression of TPH2 alone or in conjunction with TPH1 reverted the rate of reprogramming of the double mutant MEFs to the wild-type level and besides, TPH2 overexpression significantly suppressed reprogramming of wild-type MEFs. Our data thus suggest a negative role of serotonin biosynthesis in the reprogramming of somatic cells to a pluripotent state.
A Diet Containing Rutin Ameliorates Brain Intracellular Redox Homeostasis in a Mouse Model of Alzheimer’s Disease
Authors: Bermejo-Bescós Paloma , Jiménez-Aliaga Karim L. , Benedí Juana , Martín-Aragón Sagrario
Published: March 2023

Quercetin has been studied extensively for its anti-Alzheimer’s disease (AD) and anti-aging effects. Our previous studies have found that quercetin and in its glycoside form, rutin, can modulate the proteasome function in neuroblastoma cells. We aimed to explore the effects of quercetin and rutin on intracellular redox homeostasis of the brain (reduced glutathione/oxidized glutathione, GSH/GSSG), its correlation with β-site APP cleaving enzyme 1 (BACE1) activity, and amyloid precursor protein (APP) expression in transgenic TgAPP mice (bearing human Swedish mutation APP transgene, APPswe). On the basis that BACE1 protein and APP processing are regulated by the ubiquitin–proteasome pathway and that supplementation with GSH protects neurons from proteasome inhibition, we investigated whether a diet containing quercetin or rutin (30 mg/kg/day, 4 weeks) diminishes several early signs of AD. Genotyping analyses of animals were carried out by PCR. In order to determine intracellular redox homeostasis, spectrofluorometric methods were adopted to quantify GSH and GSSG levels using o-phthalaldehyde and the GSH/GSSG ratio was ascertained. Levels of TBARS were determined as a marker of lipid peroxidation. Enzyme activities of SOD, CAT, GR, and GPx were determined in the cortex and hippocampus. ΒACE1 activity was measured by a secretase-specific substrate conjugated to two reporter molecules (EDANS and DABCYL). Gene expression of the main antioxidant enzymes: APP, BACE1, a Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), caspase-3, caspase-6, and inflammatory cytokines were determined by RT-PCR. First, overexpression of APPswe in TgAPP mice decreased GSH/GSSG ratio, increased malonaldehyde (MDA) levels, and, overall, decreased the main antioxidant enzyme activities in comparison to wild-type (WT) mice. Treatment of TgAPP mice with quercetin or rutin increased GSH/GSSG, diminished MDA levels, and favored the enzyme antioxidant capacity, particularly with rutin. Secondly, both APP expression and BACE1 activity were diminished with quercetin or rutin in TgAPP mice. Regarding ADAM10, it tended to increase in TgAPP mice with rutin treatment. As for caspase-3 expression, TgAPP displayed an increase which was the opposite with rutin. Finally, the increase in expression of the inflammatory markers IL-1β and IFN-γ in TgAPP mice was lowered by both quercetin and rutin. Collectively, these findings suggest that, of the two flavonoids, rutin may be included in a day-to-day diet as a form of adjuvant therapy in AD.
COVID-19 and Cancer Diseases—The Potential of Coriolus versicolor Mushroom to Combat Global Health Challenges
Authors: Jędrzejewski Tomasz , Pawlikowska Małgorzata , Sobocińska Justyna , Wrotek Sylwia
Published: March 2023

Coriolus versicolor (CV) is a common species from the Polyporaceae family that has been used in traditional Chinese herbal medicine for over 2000 years. Among well-described and most active compounds identified in CV are polysaccharopeptides, such as polysaccharide peptide (PSP) and Polysaccharide-K (PSK, krestin), which, in some countries, are already used as an adjuvant agent in cancer therapy. In this paper, research advances in the field of anti-cancer and anti-viral action of CV are analyzed. The results of data obtained in in vitro and in vivo studies using animal models as well as in clinical research trials have been discussed. The present update provides a brief overview regarding the immunomodulatory effects of CV. A particular focus has been given to the mechanisms of direct effects of CV on cancer cells and angiogenesis. A potential use of CV compounds in anti-viral treatment, including therapy against COVID-19 disease, has also been analyzed based on the most recent literature. Additionally, the significance of fever in viral infection and cancer has been debated, providing evidence that CV affects this phenomenon.
Characterization of a PIP Binding Site in the N-Terminal Domain of V-ATPase a4 and Its Role in Plasma Membrane Association
Authors: Chu Anh , Yao Yeqi , Saffi Golam T. , Chung Ji Hyun , Botelho Roberto J. , Glibowicka Miroslawa , Deber Charles M. , Manolson Morris F.
Published: March 2023

Vacuolar ATPases (V-ATPases) are multi-subunit ATP-dependent proton pumps necessary for cellular functions, including pH regulation and membrane fusion. The evidence suggests that the V-ATPase a-subunit’s interaction with the membrane signaling lipid phosphatidylinositol (PIPs) regulates the recruitment of V-ATPase complexes to specific membranes. We generated a homology model of the N-terminal domain of the human a4 isoform (a4NT) using Phyre2.0 and propose a lipid binding domain within the distal lobe of the a4NT. We identified a basic motif, K234IKK237, critical for interaction with phosphoinositides (PIP), and found similar basic residue motifs in all four mammalian and both yeast a-isoforms. We tested PIP binding of wildtype and mutant a4NT in vitro. In protein lipid overlay assays, the double mutation K234A/K237A and the autosomal recessive distal renal tubular-causing mutation K237del reduced both PIP binding and association with liposomes enriched with PI(4,5)P2, a PIP enriched within plasma membranes. Circular dichroism spectra of the mutant protein were comparable to wildtype, indicating that mutations affected lipid binding, not protein structure. When expressed in HEK293, wildtype a4NT localized to the plasma membrane in fluorescence microscopy and co-purified with the microsomal membrane fraction in cellular fractionation experiments. a4NT mutants showed reduced membrane association and decreased plasma membrane localization. Depletion of PI(4,5)P2 by ionomycin caused reduced membrane association of the WT a4NT protein. Our data suggest that information contained within the soluble a4NT is sufficient for membrane association and that PI(4,5)P2 binding capacity is involved in a4 V-ATPase plasma membrane retention.
Knockdown of Bmp1 and Pls1 Virulence Genes by Exogenous Application of RNAi-Inducing dsRNA in Botrytis cinerea
Authors: Spada Maria , Pugliesi Claudio , Fambrini Marco , Palpacelli Diego , Pecchia Susanna
Published: March 2023

Botrytis cinerea is a pathogen of wide agronomic and scientific importance partly due to its tendency to develop fungicide resistance. Recently, there has been great interest in the use of RNA interference as a control strategy against B. cinerea. In order to reduce the possible effects on non-target species, the sequence-dependent nature of RNAi can be used as an advantage to customize the design of dsRNA molecules. We selected two genes related to virulence: BcBmp1 (a MAP kinase essential for fungal pathogenesis) and BcPls1 (a tetraspanin related to appressorium penetration). After performing a prediction analysis of small interfering RNAs, dsRNAs of 344 (BcBmp1) and 413 (BcPls1) nucleotides were synthesized in vitro. We tested the effect of topical applications of dsRNAs, both in vitro by a fungal growth assay in microtiter plates and in vivo on artificially inoculated detached lettuce leaves. In both cases, topical applications of dsRNA led to gene knockdown with a delay in conidial germination for BcBmp1, an evident growth retardation for BcPls1, and a strong reduction in necrotic lesions on lettuce leaves for both genes. Furthermore, a strongly reduced expression of the BcBmp1 and BcPls1 genes was observed in both in vitro and in vivo experiments, suggesting that these genes could be promising targets for the development of RNAi-based fungicides against B. cinerea.
Composite Coatings Based on Recombinant Spidroins and Peptides with Motifs of the Extracellular Matrix Proteins Enhance Neuronal Differentiation of Neural Precursor Cells Derived from Human Induced Pluripotent Stem Cells
Authors: Novosadova Ekaterina V. , Dolotov Oleg V. , Novosadova Lyudmila V. , Davydova Lubov I. , Sidoruk Konstantin V. , Arsenyeva Elena L. , Shimchenko Darya M. , Debabov Vladimir G. , Bogush Vladimir G. , Tarantul Vyacheslav Z.
Published: March 2023

The production and transplantation of functionally active human neurons is a promising approach to cell therapy. Biocompatible and biodegradable matrices that effectively promote the growth and directed differentiation of neural precursor cells (NPCs) into the desired neuronal types are very important. The aim of this study was to evaluate the suitability of novel composite coatings (CCs) containing recombinant spidroins (RSs) rS1/9 and rS2/12 in combination with recombinant fused proteins (FP) carrying bioactive motifs (BAP) of the extracellular matrix (ECM) proteins for the growth of NPCs derived from human induced pluripotent stem cells (iPSC) and their differentiation into neurons. NPCs were produced by the directed differentiation of human iPSCs. The growth and differentiation of NPCs cultured on different CC variants were compared with a Matrigel (MG) coating using qPCR analysis, immunocytochemical staining, and ELISA. An investigation revealed that the use of CCs consisting of a mixture of two RSs and FPs with different peptide motifs of ECMs increased the efficiency of obtaining neurons differentiated from iPSCs compared to Matrigel. CC consisting of two RSs and FPs with Arg–Gly–Asp–Ser (RGDS) and heparin binding peptide (HBP) is the most effective for the support of NPCs and their neuronal differentiation.
PPAR Pan Agonist MHY2013 Alleviates Renal Fibrosis in a Mouse Model by Reducing Fibroblast Activation and Epithelial Inflammation
Authors: Son Minjung , Kim Ga Young , Yang Yejin , Ha Sugyeong , Kim Jeongwon , Kim Doyeon , Chung Hae Young , Moon Hyung Ryong , Chung Ki Wung
Published: March 2023

The peroxisome proliferator-activated receptor (PPAR) nuclear receptor has been an interesting target for the treatment of chronic diseases. Although the efficacy of PPAR pan agonists in several metabolic diseases has been well studied, the effect of PPAR pan agonists on kidney fibrosis development has not been demonstrated. To evaluate the effect of the PPAR pan agonist MHY2013, a folic acid (FA)-induced in vivo kidney fibrosis model was used. MHY2013 treatment significantly controlled decline in kidney function, tubule dilation, and FA-induced kidney damage. The extent of fibrosis determined using biochemical and histological methods showed that MHY2013 effectively blocked the development of fibrosis. Pro-inflammatory responses, including cytokine and chemokine expression, inflammatory cell infiltration, and NF-κB activation, were all reduced with MHY2013 treatment. To demonstrate the anti-fibrotic and anti-inflammatory mechanisms of MHY2013, in vitro studies were conducted using NRK49F kidney fibroblasts and NRK52E kidney epithelial cells. In the NRK49F kidney fibroblasts, MHY2013 treatment significantly reduced TGF-β-induced fibroblast activation. The gene and protein expressions of collagen I and α-smooth muscle actin were significantly reduced with MHY2013 treatment. Using PPAR transfection, we found that PPARγ played a major role in blocking fibroblast activation. In addition, MHY2013 significantly reduced LPS-induced NF-κB activation and chemokine expression mainly through PPARβ activation. Taken together, our results suggest that administration of the PPAR pan agonist effectively prevented renal fibrosis in both in vitro and in vivo models of kidney fibrosis, implicating the therapeutic potential of PPAR agonists against chronic kidney diseases.
Adsorptive Removal of Direct Azo Dyes from Textile Wastewaters Using Weakly Basic Anion Exchange Resin
Authors: Wawrzkiewicz Monika , Kucharczyk Anna
Published: March 2023

Direct dyes are still widely used for coloring a variety of materials due to their ease of use and the wide range of colors available at a moderate cost of production. In the aquatic environment, some direct dyes, especially the azo type and their biotransformation products, are toxic, carcinogenic and mutagenic. Hence the need for their careful removal from industrial effluents. It was proposed adsorptive retention of C.I. Direct Red 23 (DR23), C.I. Direct Orange 26 (DO26) and C.I. Direct Black 22 (DB22) from effluents using anion exchange resin of tertiary amine functionalities Amberlyst A21 (A21). Applying the Langmuir isotherm model, the monolayer capacities were calculated as 285.6 mg/g for DO26 and 271.1 mg/g for DO23. The Freundlich isotherm model seems to be the better one for the description of DB22 uptake by A21, and the isotherm constant was found to be 0.609 mg1−1/n L1/n/g. The kinetic parameters revealed that the pseudo-second-order model could be used for the description of experimental data rather than the pseudo-first-order model or intraparticle diffusion model. The dye adsorption decreased in the presence of anionic and non-ionic surfactants, while their uptake was enhanced in the presence of Na2SO4 and Na2CO3. Regeneration of the A21 resin was difficult; a slight increase in its efficiency was observed using 1M HCl, 1 M NaOH and 1 M NaCl solutions in 50% v/v methanol.
Polydopamine-Based Material and Their Potential in Head and Neck Cancer Therapy—Current State of Knowledge
Authors: Witkowska Marta , Golusińska-Kardach Ewelina , Golusiński Wojciech , Florek Ewa
Published: March 2023

Head and neck cancers (HNC) are among the most common cancers in the world. In terms of frequency of occurrence in the world, HNC ranks sixth. However, the problem of modern oncology is the low specificity of the therapies used, which is why most of the currently used chemotherapeutic agents have a systemic effect. The use of nanomaterials could overcome the limitations of traditional therapies. Researchers are increasingly using polydopamine (PDA) in nanotherapeutic systems for HNC due to its unique properties. PDA has found applications in chemotherapy, photothermal therapy, targeted therapy, and combination therapies that facilitate better carrier control for the effective reduction of cancer cells than individual therapies. The purpose of this review was to present the current knowledge on the potential use of polydopamine in head and neck cancer research.
Molecular Mechanisms of Neutrophil Extracellular Trap (NETs) Degradation
Authors: Demkow Urszula
Published: March 2023

Although many studies have been exploring the mechanisms driving NETs formation, much less attention has been paid to the degradation and elimination of these structures. The NETs clearance and the effective removal of extracellular DNA, enzymatic proteins (neutrophil elastase, proteinase 3, myeloperoxidase) or histones are necessary to maintain tissue homeostasis, to prevent inflammation and to avoid the presentation of self-antigens. The persistence and overabundance of DNA fibers in the circulation and tissues may have dramatic consequences for a host leading to the development of various systemic and local damage. NETs are cleaved by a concerted action of extracellular and secreted deoxyribonucleases (DNases) followed by intracellular degradation by macrophages. NETs accumulation depends on the ability of DNase I and DNAse II to hydrolyze DNA. Furthermore, the macrophages actively engulf NETs and this event is facilitated by the preprocessing of NETs by DNase I. The purpose of this review is to present and discuss the current knowledge about the mechanisms of NETs degradation and its role in the pathogenesis of thrombosis, autoimmune diseases, cancer and severe infections, as well as to discuss the possibilities for potential therapeutic interventions. Several anti-NETs approaches had therapeutic effects in animal models of cancer and autoimmune diseases; nevertheless, the development of new drugs for patients needs further study for an effective development of clinical compounds that are able to target NETs.
A Metabolomic and Transcriptomic Study Revealed the Mechanisms of Lumefantrine Inhibition of Toxoplasma gondii
Authors: Li Meiqi , Sang Xiaoyu , Zhang Xiaohan , Li Xiang , Feng Ying , Yang Na , Jiang Tiantian
Published: March 2023

Toxoplasma gondii is an obligate protozoon that can infect all warm-blooded animals including humans. T. gondii afflicts one-third of the human population and is a detriment to the health of livestock and wildlife. Thus far, traditional drugs such as pyrimethamine and sulfadiazine used to treat T. gondii infection are inadequate as therapeutics due to relapse, long treatment period, and low efficacy in parasite clearance. Novel, efficacious drugs have not been available. Lumefantrine, as an antimalarial, is effective in killing T. gondii but has no known mechanism of action. We combined metabolomics with transcriptomics to investigate how lumefantrine inhibits T. gondii growth. We identified significant alternations in transcripts and metabolites and their associated functional pathways that are attributed to lumefantrine treatment. RH tachyzoites were used to infect Vero cells for three hours and subsequently treated with 900 ng/mL lumefantrine. Twenty-four hours post-drug treatment, we observed significant changes in transcripts associated with five DNA replication and repair pathways. Metabolomic data acquired through liquid chromatography-tandem mass spectrometry (LC-MS) showed that lumefantrine mainly affected sugar and amino acid metabolism, especially galactose and arginine. To investigate whether lumefantrine damages T. gondii DNA, we conducted a terminal transferase assay (TUNEL). TUNEL results showed that lumefantrine significantly induced apoptosis in a dose-dependent manner. Taken together, lumefantrine effectively inhibited T. gondii growth by damaging DNA, interfering with DNA replication and repair, and altering energy and amino acid metabolisms.
Classification of COVID-19 Patients into Clinically Relevant Subsets by a Novel Machine Learning Pipeline Using Transcriptomic Features
Authors: Daamen Andrea R. , Bachali Prathyusha , Grammer Amrie C. , Lipsky Peter E.
Published: March 2023

The persistent impact of the COVID-19 pandemic and heterogeneity in disease manifestations point to a need for innovative approaches to identify drivers of immune pathology and predict whether infected patients will present with mild/moderate or severe disease. We have developed a novel iterative machine learning pipeline that utilizes gene enrichment profiles from blood transcriptome data to stratify COVID-19 patients based on disease severity and differentiate severe COVID cases from other patients with acute hypoxic respiratory failure. The pattern of gene module enrichment in COVID-19 patients overall reflected broad cellular expansion and metabolic dysfunction, whereas increased neutrophils, activated B cells, T-cell lymphopenia, and proinflammatory cytokine production were specific to severe COVID patients. Using this pipeline, we also identified small blood gene signatures indicative of COVID-19 diagnosis and severity that could be used as biomarker panels in the clinical setting.
Immunogenic Properties and Antigenic Similarity of Virus-like Particles Derived from Human Polyomaviruses
Authors: Lučiūnaitė Asta , Dalgėdienė Indrė , Vasiliūnaitė Emilija , Norkienė Milda , Kučinskaitė-Kodzė Indrė , Žvirblienė Aurelija , Gedvilaitė Alma
Published: March 2023

Polyomaviruses (PyVs) are highly prevalent in humans and animals. PyVs cause mild illness, however, they can also elicit severe diseases. Some PyVs are potentially zoonotic, such as simian virus 40 (SV40). However, data are still lacking about their biology, infectivity, and host interaction with different PyVs. We investigated the immunogenic properties of virus-like particles (VLPs) derived from viral protein 1 (VP1) of human PyVs. We immunised mice with recombinant HPyV VP1 VLPs mimicking the structure of viruses and compared their immunogenicity and cross-reactivity of antisera using a broad spectrum of VP1 VLPs derived from the PyVs of humans and animals. We demonstrated a strong immunogenicity of studied VLPs and a high degree of antigenic similarity between VP1 VLPs of different PyVs. PyV-specific monoclonal antibodies were generated and applied for investigation of VLPs phagocytosis. This study demonstrated that HPyV VLPs are highly immunogenic and interact with phagocytes. Data on the cross-reactivity of VP1 VLP-specific antisera revealed antigenic similarities among VP1 VLPs of particular human and animal PyVs and suggested possible cross-immunity. As the VP1 capsid protein is the major viral antigen involved in virus-host interaction, an approach based on the use of recombinant VLPs is relevant for studying PyV biology regarding PyV interaction with the host immune system.
Privacy-Preserving Method for Trajectory Data Publication Based on Local Preferential Anonymity
Authors: Zhang Xiao , Luo Yonglong , Yu Qingying , Xu Lina , Lu Zhonghao
Published: March 2023

With the rapid development of mobile positioning technologies, location-based services (LBSs) have become more widely used. The amount of user location information collected and applied has increased, and if these datasets are directly released, attackers may infer other unknown locations through partial background knowledge in their possession. To solve this problem, a privacy-preserving method for trajectory data publication based on local preferential anonymity (LPA) is proposed. First, the method considers suppression, splitting, and dummy trajectory adding as candidate techniques. Second, a local preferential (LP) function based on the analysis of location loss and anonymity gain is designed to effectively select an anonymity technique for each anonymous operation. Theoretical analysis and experimental results show that the proposed method can effectively protect the privacy of trajectory data and improve the utility of anonymous datasets.
Colour Selection and Olfactory Responses of Papilio demoleus during Foraging and Courtship
Authors: Chen Shunan , Li Mingtao , Liu Ji , Feng Ying , Yao Jun , Shi Lei , Chen Xiaoming
Published: March 2023

Colours and odours are the most important cues for butterflies to localise food and mating partners. We studied the visual and olfactory responses of the widely distributed butterfly Papilio demoleus Linnaeus during foraging and courtship. P. demoleus visited odourless flowers with six colours except green and black, with red as the favourite colour (650–780 nm). Males and females differed in behaviour while visiting flowers. Males were more active than females during foraging. The application of honey water resulted in a significant increase in flower visits by both females and males, and they scarcely visited the apetalous branches with odours. Under natural conditions, four patterns were observed: males chasing males (42.28%), males chasing females (30.56%), females chasing females (13.73%), and females chasing males (13.43%). Males chasing males was the most frequent, probably because males drive away competing con-specific males. When butterflies visited odourless mimics, males chasing females (70.73%) and males chasing males (29.27%) also occurred, indicating that males could accurately distinguish mates using colours only without any chemical cues, and females need chemical cues. The behavioural responses of P. demoleus to floral visits and courtship suggest that colour is the dominant factor during foraging and courtship. We verified the presence of P. demoleus rhodopsin genes, including Rh2, Rh3, Rh4, and Rh5, for long wavelength, blue, and ultraviolet (UV) spectrum recognition, which is consistent with the colour recognition of flowers and wings during visiting flowers and courtship.
Religious Bodies–Lutheran Chaplains Interpreting and Asserting Religiousness of People with Severe Dementia in Finnish Nursing Homes
Authors: Pirhonen Jari , Vähäkangas Auli , Saarelainen Suvi-Maria
Published: March 2023

The prevalence of dementia is increasing globally as populations grow older. Moderate and severe dementia are the main reasons for older people entering long-term care in Finland, and the vast majority of nursing home residents have it. Regarding mild dementia, religiousness is known to slow the progress of the disease, offer solace, and maintain a life-long identity. However, we know practically nothing about the religiousness of people with severe dementia. This study sought to fill the gap by interviewing Lutheran chaplains working in Finnish nursing homes. The data were subjected to qualitative content analysis to understand: (I) how people with severe dementia may express their remaining religiousness and (II) how the chaplains asserted the religiousness of people whom their words often did not reach. The clearest expressions of religiousness found were bodily, including expressions of emotions and fumbling liturgical movements. The chaplains utilized prayer services, active presence, and generational intelligence to respond to residents’ religiousness. The main conclusion is that people with severe dementia can express their faith and are eager to practice it when opportunities are provided to do so. Our research challenges care providers and religious communities to better acknowledge the religiousness of people with severe dementia.
Can We Predict Imbalance in Patients? Analysis of the CDC National Health and Nutrition Examination Survey
Authors: Diebo Bassel G. , Stroud Sarah G. , Shah Neil V. , Messina James , Hong James M. , Alsoof Daniel , Ansari Kashif , Lafage Renaud , Passias Peter G. , Lafage Virginie , Schwab Frank J. , Paulino Carl B. , Aaron Roy , Daniels Alan H.
Published: March 2023

Understanding global body balance can optimize the postoperative course for patients undergoing spinal or lower limb surgical realignment. This observational cohort study aimed to characterize patients with reported imbalance and identify predictors. The CDC establishes a representative sample annually via the NHANES. All participants who said “yes” (Imbalanced) or “no” (Balanced) to the following question were identified from 1999–2004: “During the past 12 months, have you had dizziness, difficulty with balance or difficulty with falling?” Univariate analyses compared Imbalanced versus Balanced subjects and binary logistic regression modeling predicted for Imbalance. Of 9964 patients, imbalanced (26.5%) were older (65.4 vs. 60.6 years), with more females (60% vs. 48%). Imbalanced subjects reported higher rates of comorbidities, including osteoporosis (14.4% vs. 6.6%), arthritis (51.6% vs. 31.9%), and low back pain (54.4% vs 32.7%). Imbalanced patients had more difficulty with activities, including climbing 10 steps (43.8% vs. 21%) and stooping/crouching/kneeling (74.3% vs. 44.7%), and they needed greater time to walk 20 feet (9.5 vs. 7.1 s). Imbalanced subjects had significantly lower caloric and dietary intake. Regression revealed that difficulties using fingers to grasp small objects (OR: 1.73), female gender (OR: 1.43), difficulties with prolonged standing (OR: 1.29), difficulties stooping/crouching/kneeling (OR: 1.28), and increased time to walk 20 feet (OR: 1.06) were independent predictors of Imbalance (all p < 0.05). Imbalanced patients were found to have identifiable comorbidities and were detectable using simple functional assessments. Structured tests that assess dynamic functional status may be useful for preoperative optimization and risk-stratification for patients undergoing spinal or lower limb surgical realignment.
Clinical Relevance of Uterine Manipulation on Oncologic Outcome in Robot-Assisted versus Open Surgery in the Management of Endometrial Cancer
Authors: Eoh Kyung Jin , Kim Yoo-Na , Nam Eun Ji , Kim Sang Wun , Kim Young Tae
Published: March 2023

In this study, we investigated the impact of uterine manipulation on endometrial cancer survival outcomes. We analyzed patients with endometrial cancer who underwent robot-assisted staging and open staging surgery between 2010 and 2020. Either uterine manipulators or vaginal tubes were utilized in robot-assisted staging. Propensity score matching was performed to correct baseline characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier curve analysis. In total, 574 patients, including those undergoing robot-assisted staging with a uterine manipulator (n = 213) or vaginal tube (n = 147) and staging laparotomy (n = 214), were analyzed. Propensity score matching was performed for age, histology, and stage as covariates. Before matching, Kaplan–Meier curve analysis showed that PFS and OS were significantly different among the three groups (p < 0.001 and p = 0.009, respectively). In the propensity-matched cohorts of 147 women, the previously suggested differences in PFS and OS were not observed in patients undergoing robot-assisted staging with a uterine manipulator or vaginal tube or open surgery. In conclusion, robotic surgery using a uterine manipulator or vaginal tube did not compromise survival outcomes in endometrial cancer management.