bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Characterization of Biomimetic Functional Scaffold with Gradient Structure for Osteochondral Defect Repair
Authors: Chen Li , Wei Li , Su Xudong , Qin Leilei , Xu Zhenghao , Huang Xiao , Chen Hong , Hu Ning
Published: February 2023

Osteochondral (OC) defects cannot adequately repair themselves due to their sophisticated layered structure and lack of blood supply in cartilage. Although therapeutic interventions are reaching an advanced stage, current clinical therapies to repair defects are in their infancy. Among the possible therapies, OC tissue engineering has shown considerable promise, and multiple approaches utilizing scaffolds, cells, and bioactive factors have been pursued. The most recent trend in OC tissue engineering has been to design gradient scaffolds using different materials and construction strategies (such as bi-layered, multi-layered, and continuous gradient structures) to mimic the physiological and mechanical properties of OC tissues while further enabling OC repair. This review focuses specifically on design and construction strategies for gradient scaffolds and their role in the successful engineering of OC tissues. The current dilemmas in the field of OC defect repair and the efforts of tissue engineering to address these challenges were reviewed. In addition, the advantages and limitations of the typical fabrication techniques for gradient scaffolds were discussed, with examples of recent studies summarizing the future prospects for integrated gradient scaffold construction. This updated and enlightening review could provide insights into our current understanding of gradient scaffolds in OC tissue engineering.
Peptides in Dentistry: A Scoping Review
Authors: Hardan Louis , Chedid Jean Claude Abou , Bourgi Rim , Cuevas-Suárez Carlos Enrique , Lukomska-Szymanska Monika , Tosco Vincenzo , Monjarás-Ávila Ana Josefina , Jabra Massa , Salloum-Yared Fouad , Kharouf Naji , Mancino Davide , Haikel Youssef
Published: February 2023

Currently, it remains unclear which specific peptides could be appropriate for applications in different fields of dentistry. The aim of this scoping review was to scan the contemporary scientific papers related to the types, uses and applications of peptides in dentistry at the moment. Literature database searches were performed in the following databases: PubMed/MEDLINE, Scopus, Web of Science, Embase, and Scielo. A total of 133 articles involving the use of peptides in dentistry-related applications were included. The studies involved experimental designs in animals, microorganisms, or cells; clinical trials were also identified within this review. Most of the applications of peptides included caries management, implant osseointegration, guided tissue regeneration, vital pulp therapy, antimicrobial activity, enamel remineralization, periodontal therapy, the surface modification of tooth implants, and the modification of other restorative materials such as dental adhesives and denture base resins. The in vitro and in vivo studies included in this review suggested that peptides may have beneficial effects for treating early carious lesions, promoting cell adhesion, enhancing the adhesion strength of dental implants, and in tissue engineering as healthy promotors of the periodontium and antimicrobial agents. The lack of clinical trials should be highlighted, leaving a wide space available for the investigation of peptides in dentistry.
Competitiveness and Phylogenetic Relationship of Rhizobial Strains with Different Symbiotic Efficiency in Trifolium repens: Conversion of Parasitic into Non-Parasitic Rhizobia by Natural Symbiotic Gene Transfer
Authors: Morel Revetria María A. , Berais-Rubio Andrés , Giménez Matías , Sanjuán Juan , Signorelli Santiago , Monza Jorge
Published: February 2023

In Uruguayan soils, populations of native and naturalized rhizobia nodulate white clover. These populations include efficient rhizobia but also parasitic strains, which compete for nodule occupancy and hinder optimal nitrogen fixation by the grassland. Nodulation competitiveness assays using gusA-tagged strains proved a high nodule occupancy by the inoculant strain U204, but this was lower than the strains with intermediate efficiencies, U268 and U1116. Clover biomass production only decreased when the parasitic strain UP3 was in a 99:1 ratio with U204, but not when UP3 was at equal or lower numbers than U204. Based on phylogenetic analyses, strains with different efficiencies did not cluster together, and U1116 grouped with the parasitic strains. Our results suggest symbiotic gene transfer from an effective strain to U1116, thereby improving its symbiotic efficiency. Genome sequencing of U268 and U204 strains allowed us to assign them to species Rhizobium redzepovicii, the first report of this species nodulating clover, and Rhizobium leguminosarun, respectively. We also report the presence of hrrP- and sapA-like genes in the genomes of WSM597, U204, and U268 strains, which are related to symbiotic efficiency in rhizobia. Interestingly, we report here chromosomally located hrrP-like genes.
Transcriptional Analysis of the Endostyle Reveals Pharyngeal Organ Functions in Ascidian
Authors: Jiang An , Zhang Wei , Wei Jiankai , Liu Penghui , Dong Bo
Published: February 2023

The endostyle is a pharyngeal organ with an opening groove and cilia in invertebrate chordates (amphioxus and ascidian) and cyclostomate (lamprey), serving as a filter-feeding tract and thyroid-secreting location. Emerging evidence implies its complex cellular composition and potentially versatile functions. Multiple cell types in the endostyle have been thought to be progenitors of complex organs in advanced vertebrates. To describe the expression profile and the potential functions, bulk RNA sequencing on the endostyle in ascidian Styela clava was conducted and distinct markers were selected by multileveled comparative analysis. Transcriptional data assay and qRT-PCR-verified results showed the regional expression patterns of Hox genes in the longitudinal axis. Organ-specific markers of the endostyle was proposed by comparing expression with the main organs of the ascidian. A cross-species transcriptional profile projection between the endostyle and organs from Danio rerio and Homo sapiens indicates a robust homogenous relationship to the thyroid and digestive system of the endostyle. The high similarity between the endostyle and the head kidney in zebrafish/the bone marrow in human implies uniquely profound functions of the pharyngeal organ in proto-vertebrates. Our result revealed that the transcriptional profile of the human parathyroid gland was similar to the ascidian endostyle, indicating the evolutionary origin of vertebrate hormone secretion organs.
Submerged and Solid-State Fermentation of Spirulina with Lactic Acid Bacteria Strains: Antimicrobial Properties and the Formation of Bioactive Compounds of Protein Origin
Authors: Tolpeznikaite Ernesta , Bartkevics Vadims , Skrastina Anna , Pavlenko Romans , Ruzauskas Modestas , Starkute Vytaute , Zokaityte Egle , Klupsaite Dovile , Ruibys Romas , Rocha João Miguel , Bartkiene Elena
Published: February 2023

The aim of this study was to investigate the changes in bioactive compounds (L-glutamic acid (L-Glu), gamma-aminobutyric acid (GABA) and biogenic amines (BAs)) during the submerged (SMF) and solid-state (SSF) fermentation of Spirulina with lactobacilli strains (Lacticaseibacillus paracasei No. 244; Levilactobacillus brevis No. 173; Leuconostoc mesenteroides No. 225; Liquorilactobacillus uvarum No. 245). The antimicrobial properties of the untreated and fermented Spirulina against a variety of pathogenic and opportunistic strains were tested. The highest concentrations of L-Glu (3841 mg/kg) and GABA (2396 mg/kg) were found after 48 h of SSF with No. 173 and No. 244 strains, respectively. The LAB strain used for biotreatment and the process conditions, as well as the interaction of these factors, had statistically significant effects on the GABA concentration in Spirulina (p ≤ 0.001, p = 0.019 and p = 0.011, respectively). In all cases, the SSF of Spirulina had a higher total BA content than SMF. Most of the fermented Spirulina showed exceptional antimicrobial activity against Staphylococcus aureus but not against the other pathogenic bacteria. The ratios of BA/GABA and BA/L-Glu ranged from 0.5 to 62 and from 0.31 to 10.7, respectively. The GABA content was correlated with putrescine, cadaverine, histamine, tyramine, spermidine and spermine contents. The L-glutamic acid concentration showed positive moderate correlations with tryptamine, putrescine, spermidine and spermine. To summarize, while high concentrations of desirable compounds are formed during fermentation, the formation of non-desirable compounds (BAs) must also be considered due to the similar mechanism of their synthesis as well as the possibility of obtaining high concentrations in the end products.
Epigenetic Regulation of miR-25 and Lnc107153 on Expression of Seasonal Estrus Key Gene CHGA in Sheep
Authors: Di Ran , Fan Yekai , He Xiaoyun , Liu Qiuyue , Wang Xiangyu , Gong Yiming , Mwacharo Joram Mwashigadi , Wei Caihong , Liu Yufang , Chu Mingxing
Published: February 2023

Pituitary pars tuberalis (PT) plays an important role as the transmission center in the seasonal reproduction of animals. It helps convert external photoperiod signals into intrinsic seasonal reproduction signals. In sheep PT, specific expression patterns of several genes (including short photoperiod-induced gene CHGA and long photoperiod genes EYA3 and TSHβ) under different photoperiods are crucial characteristics during this signal transduction. Recent studies have revealed the role of epigenetics in regulating the expression of seasonal reproductive key genes. Therefore, we explored whether microRNAs and LncRNAs regulated the expressions of the above key genes. Firstly, the expression of miR-25 and CHGA showed a significant negative correlation in sheep PT. Results of the dual luciferase reporter assay and miR-25 overexpression indicated that miR-25 could inhibit the expression of CHGA by specifically binding to its 3′UTR region in pituitary cells. Then, expression negative correlation and dual luciferase reporter analyses were used to screen and identify the candidate LncRNA (Lnc107153) targeted by miR-25. Finally, the results of fluorescence in situ hybridization and Lnc107153 overexpression suggested that Lnc107153 and miR-25 were involved in the epigenetic regulation of CHGA expression. However, the expressions of EYA3 and TSHβ were not regulated by miRNAs. These results will provide new insights into the epigenetic regulatory network of key genes in sheep seasonal reproduction.
Effect of Seawall Embankment Reclamation on the Distribution of Cr, Cu, Pb and Zn Pollution in Invasive Spartina alterniflora and Native Phragmites australis Coastal Saltmarshes of East China
Authors: Li Jian , Leng Zhanrui , Jia Hui , Wei Lili , Yuguda Taitiya Kenneth , Du Daolin
Published: February 2023

Coastal reclamation by seawall embankments and the spread of invasive C4 perennial grass Spartina alterniflora have recently become more prevalent in eastern China’s coastal wetlands. While trace metals (TMs), carbon, and nitrogen dynamics concerning reclamation have extensively been explored across China’s coastal wetlands, to date, the impact of reclamation by coastal embankment and exotic plant invasion on TMs’ pollution dynamics in coastal marshes remains largely unexplored. We compared TMs Cr, Cu, Pb, and Zn cumulation in coastal embankment-reclaimed versus unreclaimed S. alterniflora and Phragmites australis saltmarshes in eastern China coastal wetlands. In both S. alterniflora and P. australis marshes, coastal embankment reclamation spurred an increase in Cr, Cu, Pb, and Zn concentrations by 31.66%, 53.85%, 32.14%, 33.96% and by 59.18%, 87.50%, 55.55%, 36.84%, respectively, in both marsh types. Reclamation also reduced plant biomass, soil moisture, and soil salinity in both plants’ marshes. Our findings suggest that the impact of coastal embankment reclamation and replacement of native saltmarshes by invasive S. alterniflora had a synergistic effect on TM accumulation in the P. australis marshes, as corroborated by bioaccumulation and translocation factors. Reclamation by coastal embankments and invasive alien plants could significantly impair the physico-chemical properties of native plant saltmarsh and essentially weaken the accumulation of Cr, Cu, Pb, and Zn potential of the coastal saltmarshes. Our findings provide policymakers with an enhanced knowledge of the relationship between reclamation, plant invasiveness, and TM pollution dynamics in coastal wetlands, providing a baseline for attaining future goals and strategies related to the tradeoffs of various wetland reclamation types.
Remodeling of the Platynereis Musculature during Sexual Maturation
Authors: Dahlitz Ina , Dorresteijn Adriaan , Holz Anne
Published: February 2023

Background: The external transformations associated with sexual maturation in Platynereis dumerilii (Audouin and Milne Edwards) are well studied, whereas the internal changes along the body axis have not been systematically analyzed. Therefore, we examined muscle morphology in body regions located anterior or posterior to the prospective atokous/epitokous border to generate a structural basis for internal transformations. Results: All dorsal and ventral longitudinal muscles were significantly reduced in size and density after sexual maturation and strongly atrophied, with the greatest decrease in the anterior segments of females. Despite the general reduction in size throughout the longitudinal muscles, we found a specific degradation mechanism for the posterior segments, which were characterized by the formation of secondary bundle-like fibrous structures. In addition, we observed a profound remodeling of the transversal muscles in the posterior segments of both sexes, apparently resulting in excessive thickening of these muscles. Accordingly, the entire transversal muscle complex was severely swollen and ultrastructurally characterized by a greatly increased number of mitochondria. As a possible trigger for this remodeling, we discovered an enormous number of small, blind-ending blood vessels that completely penetrated the longitudinal and transversal muscles in posterior segments. In addition, both the number of visceral muscles as well as their coelothelial covering were reduced during sexual maturation. Conclusions: We hypothesize that a possible reason for the secondary bundling of the longitudinal fibers, as well as the difference in size of the posterior transversal muscles, could be the high degree of posterior vascularization. The different degree of muscle remodeling thus depends on segmental affiliation and reflects the tasks in the motility of the different body regions after maturation. The strongest atrophy was found in the anterior segments, while signs of redifferentiation were encountered in posterior segments, supported by the vigorous growth of vessels supplying the transformed epitokous parapodia and associated muscles, which allows rapid swimming during swarming and gamete release.
Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors
Authors: Speina Elżbieta , Wilczek Marcin , Mieczkowski Adam
Published: February 2023

Benzodiazepines that consist of one α- and one β-amino acid residues linked together in a seven-membered heterocyclic ring could be treated as small, rigid, cyclic dipeptides capable of exhibiting a wide range of biological activities. During our research on novel analogues of anthramycin, a tricyclic antibiotic benzodiazepine, we developed the synthesis of two benzodiazepine dimers, obtained through the cyclization of appropriate linear tripeptides. The synthesized compounds were tested on a panel of seven cancer and normal cell lines. The developed molecules exhibited promising cytotoxic activity against the lung cancer cell lines A549 and NCI-H1299 and the epidermoid carcinoma cell line A-431. Moreover, they showed significant selectivity compared to the reference cell lines (BJ—human normal skin fibroblasts and MRC-5—human normal lung cell line). When tested on two isogenic cell lines, HCT116 and HCT116p53−/− (colon cancer), contrary to cisplatin being used as a positive control, the obtained compounds showed a cytotoxic effect independent of the p53 protein status. For the above reasons, the obtained compounds can be considered a new group of promising anticancer agents, useful in the fight against p53-dependent drug resistance in cancers. They can also be treated as convenient, leading structures suitable for further optimization and searching for more active and selective molecules.
G4Beacon: An In Vivo G4 Prediction Method Using Chromatin and Sequence Information
Authors: Zhang Zhuofan , Zhang Rongxin , Xiao Ke , Sun Xiao
Published: February 2023

G-quadruplex (G4) structures are critical epigenetic regulatory elements, which usually form in guanine-rich regions in DNA. However, predicting the formation of G4 structures within living cells remains a challenge. Here, we present an ultra-robust machine learning method, G4Beacon, which utilizes the Gradient-Boosting Decision Tree (GBDT) algorithm, coupled with the ATAC-seq data and the surrounding sequences of in vitro G4s, to accurately predict the formation ability of these in vitro G4s in different cell types. As a result, our model achieved excellent performance even when the test set was extremely skewed. Besides this, G4Beacon can also identify the in vivo G4s of other cell lines precisely with the model built on a special cell line, regardless of the experimental techniques or platforms. Altogether, G4Beacon is an accurate, reliable, and easy-to-use method for the prediction of in vivo G4s of various cell lines.
Molecular Characteristics of Toxicity of Acrolein Produced from Spermine
Authors: Kashiwagi Keiko , Igarashi Kazuei
Published: February 2023

Acrolein (CH2=CH-CHO), an unsaturated aldehyde produced from spermine, is one of the major contributors to oxidative stress. Acrolein has been found to be more toxic than reactive oxygen species (H2O2 and •OH), and it can be easily conjugated with proteins, bringing about changes in nature of the proteins. Acrolein is detoxified by glutathione in cells and was found to be mainly produced from spermine through isolating two cell lines of acrolein-resistant Neuro2a cells. The molecular characteristics of acrolein toxicity and tissue damage elicited by acrolein were investigated. It was found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH); cytoskeleton proteins such as vimentin, actin, α- and β-tubulin proteins; and apolipoprotein B-100 (ApoB100) in LDL are strongly damaged by acrolein conjugation. In contrast, activities of matrix metalloproteinase-9 (MMP-9) and proheparanase (proHPSE) are enhanced, and antibody-recognizing abilities of immunoglobulins are modified by acrolein conjugation, resulting in aggravation of diseases. The functional changes of these proteins by acrolein have been elucidated at the molecular level. The findings confirmed that acrolein is the major contributor causing tissue damage in the elderly.
Immunological and Structural Characterization of Titin Main Immunogenic Region; I110 Domain Is the Target of Titin Antibodies in Myasthenia Gravis
Authors: Stergiou Christos , Williams Rhys , Fleming Jennifer R. , Zouvelou Vasiliki , Ninou Elpinickie , Andreetta Francesca , Rinaldi Elena , Simoncini Ornella , Mantegazza Renato , Bogomolovas Julius , Tzartos John , Labeit Siegfried , Mayans Olga , Tzartos Socrates
Published: February 2023

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction (NJ) of skeletal muscles. The major MG autoantigen is nicotinic acetylcholine receptor. Other autoantigens at the NJ include MuSK, LRP4 and agrin. Autoantibodies to the intra-sarcomeric striated muscle-specific gigantic protein titin, although not directed to the NJ, are invaluable biomarkers for thymoma and MG disease severity. Thymus and thymoma are critical in MG mechanisms and management. Titin autoantibodies bind to a 30 KDa titin segment, the main immunogenic region (MIR), consisting of an Ig-FnIII-FnIII 3-domain tandem, termed I109–I111. In this work, we further resolved the localization of titin epitope(s) to facilitate the development of more specific anti-titin diagnostics. For this, we expressed protein samples corresponding to 8 MIR and non-MIR titin fragments and tested 77 anti-titin sera for antibody binding using ELISA, competition experiments and Western blots. All anti-MIR antibodies were bound exclusively to the central MIR domain, I110, and to its containing titin segments. Most antibodies were bound also to SDS-denatured I110 on Western blots, suggesting that their epitope(s) are non-conformational. No significant difference was observed between thymoma and non-thymoma patients or between early- and late-onset MG. In addition, atomic 3D-structures of the MIR and its subcomponents were elucidated using X-ray crystallography. These immunological and structural data will allow further studies into the atomic determinants underlying titin-based autoimmunity, improved diagnostics and how to eventually treat titin autoimmunity associated co-morbidities.
Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines
Authors: Bellavite Paolo , Ferraresi Alessandra , Isidoro Ciro
Published: February 2023

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system. ACE2 is present as membrane-bound on several cell types, including the mucosa of the upper respiratory and of the gastrointestinal tracts, the endothelium, the platelets, and in soluble form in the plasma. The ACE2 enzyme converts the vasoconstrictor angiotensin II into peptides with vasodilator properties. Here we review the pathways for immunization and the molecular mechanisms through which the Spike protein, either from SARS-CoV-2 or encoded by the mRNA-based vaccines, interferes with the Renin-Angiotensin-System governed by ACE2, thus altering the homeostasis of the circulation and of the cardiovascular system. Understanding the molecular interactions of the Spike protein with ACE2 and the consequent impact on cardiovascular system homeostasis will direct the diagnosis and therapy of the vaccine-related adverse effects and provide information for development of a personalized vaccination that considers pathophysiological conditions predisposing to such adverse events.
Holistic View on the Structure of Immune Response: Petri Net Model
Authors: Scharf Sonja , Ackermann Jörg , Bender Leonie , Wurzel Patrick , Schäfer Hendrik , Hansmann Martin-Leo , Koch Ina
Published: February 2023

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell–cell interactions or have to make assumptions about parameters. The broad variation of, e.g., the dimensions and abundance between lymph nodes as well as between individual patients hampers conclusive quantitative modeling. No theoretical model has been established representing a consensus on the set of major cellular processes involved in the immune response. In this paper, we apply the Petri net formalism to construct a semi-quantitative mathematical model of the lymph nodes. The model covers the major cellular processes of immune response and fulfills the formal requirements of Petri net models. The intention is to develop a model taking into account the viewpoints of experienced pathologists and computer scientists in the field of systems biology. In order to verify formal requirements, we discuss invariant properties and apply the asynchronous firing rule of a place/transition net. Twenty-five transition invariants cover the model, and each is assigned to a functional mode of the immune response. In simulations, the Petri net model describes the dynamic modes of the immune response, its adaption to antigens, and its loss of memory.
Synthesis, Characterization and Biocompatibility Evaluation of Novel Chitosan Lipid Micro-Systems for Modified Release of Diclofenac Sodium
Authors: Pauna Ana-Maria Raluca , Mititelu Tartau Liliana , Bogdan Maria , Meca Andreea-Daniela , Popa Gratiela Eliza , Pelin Ana Maria , Drochioi Cristian Ilie , Pricop Daniela Angelica , Pavel Liliana Lacramioara
Published: February 2023

The purpose of our study was the obtaining, characterization and biocompatibility estimation of novel carrier systems for diclofenac. Diclofenac is a potent nonsteroidal anti-inflammatory drug with frequent gastrointestinal side effects, impairing the quality of the patient’s life. Original diclofenac-loaded micro-vesicles coated with chitosan were prepared and physico-chemical analyzed. We investigated their in vitro hemocompatibility and in vivo biocompatibility in rats. The animals were treated orally as follows: group 1 (Control): distilled water 0.3 mL/100 g body weight; Group 2 (CHIT): 0.3 mL/100 g body weight 0.5% chitosan solution; Group 3 (DCF): 15 mg/kg body weight diclofenac; Group 4 (DCF-ves): lipid vesicles loaded with diclofenac 15 mg/kg body weight. Blood samples were collected for assessing: red blood cells, hemoglobin, hematocrit and leukocyte formula. A series of specific parameters of the liver and kidney function, some markers of immune defense, as well as the activity of some enzymes involved in oxidative processes, were also investigated. At the end of the experiment, the animals were sacrificed and fragments of liver, kidney and stomach were collected for histopathological examination. No blood hemolysis was evidenced by the in vitro test with the administration of diclofenac vesicles. The animals treated with diclofenac lipid vesicles stabilized with chitosan did not display any notable differences in their hematological and biochemical profile compared to control animals. These data correlated with the histological results, which showed the absence of architectural changes in the examined tissues. Biological in vitro and in vivo evaluation revealed that the microvesicles containing diclofenac are biocompatible, with potential to be used as delivery systems to modify the drug release, thus making them an attractive candidate for biomedical applications.
The Inflammatory Signals Associated with Psychosis: Impact of Comorbid Drug Abuse
Authors: Herrera-Imbroda Jesús , Flores-López María , Ruiz-Sastre Paloma , Gómez-Sánchez-Lafuente Carlos , Bordallo-Aragón Antonio , Rodríguez de Fonseca Fernando , Mayoral-Cleríes Fermín
Published: February 2023

Psychosis and substance use disorders are two diagnostic categories whose association has been studied for decades. In addition, both psychosis spectrum disorders and drug abuse have recently been linked to multiple pro-inflammatory changes in the central nervous system. We have carried out a narrative review of the literature through a holistic approach. We used PubMed as our search engine. We included in the review all relevant studies looking at pro-inflammatory changes in psychotic disorders and substance use disorders. We found that there are multiple studies that relate various pro-inflammatory lipids and proteins with psychosis and substance use disorders, with an overlap between the two. The main findings involve inflammatory mediators such as cytokines, chemokines, endocannabinoids, eicosanoids, lysophospholipds and/or bacterial products. Many of these findings are present in different phases of psychosis and in substance use disorders such as cannabis, cocaine, methamphetamines, alcohol and nicotine. Psychosis and substance use disorders may have a common origin in an abnormal neurodevelopment caused, among other factors, by a neuroinflammatory process. A possible convergent pathway is that which interrelates the transcriptional factors NFκB and PPARγ. This may have future clinical implications.
Effects of Interleukin-1 Genotype on the Clinical Efficacy of Non-Surgical Periodontal Treatment of Polish Patients with Periodontitis
Authors: Brodzikowska Aniela , Górski Bartłomiej , Bogusławska-Kapała Agnieszka
Published: February 2023

(1) Background: Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus. The aim of the study was to evaluate the efficacy of basic periodontal treatment depending on the interleukin-1 genotype in adult Poles. (2) Methods: Sixty subjects aged 39–64 years were examined. At initial presentation (T1), at 6–8 weeks (T2), and 16–18 weeks (T3) after treatment completion, the following percentages were recorded: surfaces with plaque, pockets bleeding, pocket depth, and change in the attachment level. During the T1 examination, the genotype for IL-1 was determined using the GenoType® PST test. (3) Results: Thirty subjects had genotype IL+ and the other thirty were IL−. During the T1 examination no significant differences were observed between patients. The study showed an increase of all the tested clinical parameters after 6–8 weeks. This increase continued up to the T3 examination. A significant reduction in the percentage of plaque surfaces after 6–8 weeks was observed, which was sustained after 16–18 weeks for both genotypes. For both genotypes, a significant decrease in the percentage of bleeding pockets was observed at the T2 examination, which persisted through until examination T3. For both studied genotypes, after 6–8 weeks, a significant shallowing of pockets was observed. In patients with the IL− genotype, a further significant shallowing of pockets was observed after 16–18 weeks. A significant reconstruction of epithelial attachment was observed between the T1 and T2 examinations, averaging 0.55 mm in patients with the IL+ genotype, and 0.77 in patients with the IL− genotype. (4) Conclusions: The results of our study show that the IL-1 genotype, may be one of the factors affecting the healing process after non-surgical periodontal treatment in adult Poles.
The Impact of SGLT2 Inhibitor Dapagliflozin on Adropin Serum Levels in Men and Women with Type 2 Diabetes Mellitus and Chronic Heart Failure
Authors: Berezin Alexander A. , Obradovic Zeljko , Fushtey Ivan M. , Berezina Tetiana A. , Novikov Evgen V. , Schmidbauer Lukas , Lichtenauer Michael , Berezin Alexander E.
Published: February 2023

Background: adropin plays a protective role in cardiac remodeling through supporting energy metabolism and water homeostasis and suppressing inflammation. Low circulating levels of adropin were positively associated with the risk of cardiovascular diseases and type 2 diabetes mellitus (T2DM). We hypothesized that sodium–glucose linked transporter 2 (SGLT2) inhibitor dapagliflosin might represent cardiac protective effects in T2DM patients with known chronic HF through the modulation of adropin levels. Methods: we prospectively enrolled 417 patients with T2DM and HF from an entire cohort of 612 T2DM patients. All eligible patients were treated with the recommended guided HF therapy according to their HF phenotypes, including SGLT2 inhibitor dapagliflozin 10 mg, daily, orally. Anthropometry, clinical data, echocardiography/Doppler examinations, and measurements of biomarkers were performed at the baseline and over a 6-month interval of SGLT2 inhibitor administration. Results: in the entire group, dapagliflozin led to an increase in adropin levels by up to 26.6% over 6 months. In the female subgroup, the relative growth (Δ%) of adropin concentrations was sufficiently higher (Δ% = 35.6%) than that in the male subgroup (Δ% = 22.7%). A multivariate linear regression analysis of the entire group showed that the relative changes (Δ) in the left ventricular (LV) ejection fraction (LVEF), left atrial volume index (LAVI), and E/e’ were significantly associated with increased adropin levels. In the female subgroup, but not in the male subgroup, ΔLVEF (p = 0.046), ΔLAVI (p = 0.001), and ΔE/e’ (p = 0.001) were independent predictive values for adropin changes. Conclusion: the levels of adropin seem to be a predictor for the favorable modification of hemodynamic performances during SGLT2 inhibition, independent ofN-terminal brain natriuretic pro-peptide levels.
Development of a TGFβ—IL-2/15 Switch Receptor for Use in Adoptive Cell Therapy
Authors: Beck Carole , Casey Nicholas Paul , Persiconi Irene , Moharrami Neda Nejati , Sike Adam , Jin Yixin , Kyte Jon Amund
Published: February 2023

Therapy employing T cells modified with chimeric antigen receptors (CARs) is effective in hematological malignancies but not yet in solid cancers. CAR T cell activity in solid tumors is limited by immunosuppressive factors, including transforming growth factor β (TGFβ). Here, we describe the development of a switch receptor (SwR), in which the extracellular domains of the TGFβ receptor are fused to the intracellular domains from the IL-2/15 receptor. We evaluated the SwR in tandem with two variants of a CAR that we have developed against STEAP1, a protein highly expressed in prostate cancer. The SwR-CAR T cell activity was assessed against a panel of STEAP1+/− prostate cancer cell lines with or without over-expression of TGFβ, or with added TGFβ, by use of flow cytometry cytokine and killing assays, Luminex cytokine profiling, cell counts, and flow cytometry phenotyping. The results showed that the SwR-CAR constructs improved the functionality of CAR T cells in TGFβ-rich environments, as measured by T cell proliferation and survival, cytokine response, and cytotoxicity. In assays with four repeated target-cell stimulations, the SwR-CAR T cells developed an activated effector memory phenotype with retained STEAP1-specific activity. In conclusion, the SwR confers CAR T cells with potent and durable in vitro functionality in TGFβ-rich environments. The SwR may be used as an add-on construct for CAR T cells or other forms of adoptive cell therapy.
Human Xylosyltransferase I—An Important Linker between Acute Senescence and Fibrogenesis
Authors: Schmidt Vanessa , Ohmes Justus , Ly Thanh-Diep , Fischer Bastian , Kleine Anika , Knabbe Cornelius , Faust-Hinse Isabel
Published: February 2023

The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation. Furthermore, XT-I overexpression is associated with fibrosis, whereby a fibrotic process initially develops from a dysregulated wound healing. In a physiologically wound healing process, extracellular matrix-producing myofibroblasts enter acute senescence to protect against fibrosis. The aim of this study was to determine the role of XT-I in acute senescent proto-myofibroblasts. Normal human dermal fibroblasts were seeded in a low cell density to promote myofibroblast differentiation and treated with H2O2 to induce acute senescence. Initiation of the acute senescence program in human proto-myofibroblasts resulted in a suppression of XYLT mRNA expression compared to the control, whereby the isoform XYLT1 was more affected than XYLT2. Moreover, the XT-I protein expression and enzyme activity were also reduced in H2O2-treated cells compared to the control. The examination of extracellular matrix remodeling revealed reduced expression of collagen I, fibronectin and decorin. In summary, acute senescent proto-myofibroblasts formed an anti-fibrotic phenotype, and suppression of XT-I during the induction process of acute senescence significantly contributed to subsequent ECM remodeling. XT-I therefore plays an important role in the switch between physiological and pathological wound healing.
Anti-Inflammatory Effects of Allocryptopine via the Target on the CX3CL1–CX3CR1 axis/GNB5/AKT/NF-κB/Apoptosis in Dextran Sulfate-Induced Mice
Authors: Yang Yang , Ding Tingyu , Xiao Gang , Huang Jialu , Luo Dan , Yue Meishan , Su Yue , Jiang Sujuan , Zeng Jianguo , Liu Yisong
Published: February 2023

Allocryptopine (ALL) is an isoquinoline alkaloid extracted from Macleaya cordata(Willd). R. Br., which has been claimed to have anti-inflammatory and neuroprotection properties. However, the mechanism by which ALL ameliorates inflammatory bowel disease (IBD) remains unclear. Here, we used network pharmacology and quantitative proteomic approaches to investigate the effect of ALL on IBD pathogenesis. Network pharmacology predicted potential targets and signaling pathways of ALL’s anti-IBD effects. As predicted by network pharmacology, gene ontology (GO) analysis, in terms of the proteomic results, showed that the immune response in mucosa and antimicrobial humoral response were enriched. Further study revealed that the ALL-related pathways were the chemokine signaling pathway and apoptosis in the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, we identified AKT1 as a hub for the critical pathways through protein–protein interaction (PPI) network analysis. Similar to mesalazine (MES), Western blot verified that ALL downregulated upstream chemokine CX3CL1 and GNB5 content to reduce phosphorylation of AKT and NF-κB, as well as the degree of apoptosis, to improve inflammatory response in the colon. Our research may shed light on the mechanism by which ALL inhibits the CX3CL1/GNB5/AKT2/NF-κB/apoptosis pathway and improves the intestinal barrier to reduce colitis response and act on the CX3CL1–CX3CR1 axis to achieve neuroprotection.
Micro Ribonucleic Acid−29a (miR−29a) Antagonist Normalizes Bone Metabolism in Osteogenesis Imperfecta (OI) Mice Model
Authors: Ko Jih-Yang , Wang Feng-Sheng , Chen Sung-Hsiung , Kuo Shu-Jui
Published: February 2023

Osteogenesis imperfecta (OI) is not curative nowadays. This study tried to unriddle the therapeutic potential of micro ribonucleic acid-29a (miR-29a) antagonist in treating OI in a mouse animal model (B6C3Fe a/a-Col1a2oim/J). We showed that the expression levels of miR-29a were higher in bone tissues obtained from the OI mice than from wild-type mice demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization assay. We established lentivirus-shuttled vector expressing miR-29a antisense oligonucleotide (miR-29a-AS) and miR-29a precursors (pre-miR-29a), showing that the inferior bony architecture in micro-computed tomography and pertinent morphometric parameters could be rescued by miR-29a-AS and deteriorated by pre-miR-29a. The decreased proliferating cell nuclear antigen (PCNA), increased Dickkopf-1 (DKK1), and decreased β-catenin expression in OI mice could be accentuated by pre-miR-29a and normalized by miR-29a-AS. The decreased osteogenesis and increased osteoclastogenesis in OI mice could also be accentuated by pre-miR-29a and normalized by miR-29a-AS. miR-29a-AS did not seem to possess severe hepatic or renal toxicities.
Analyzing the Differential Impact of Semen Preparation Methods on the Outcomes of Assisted Reproductive Techniques
Authors: Bibi Riffat , Jahan Sarwat , Afsar Tayyaba , Almajwal Ali , Hammadeh Mohamad Eid , Amor Houda , Abusharha Ali , Razak Suhail
Published: February 2023

Sperm separation plays a critical role in assisted reproductive technology. Based on migration, density gradient centrifugation and filtration, a properly selected sperm could help in increasing assisted reproductive outcomes in teratozoospermia (TZs). The current study aimed to assess the prognostic value of four sperm selection techniques: density gradient centrifugation (DGC), swim-up (SU), DGC-SU and DGC followed by magnetic-activated cell sorting (DGC-MACS). These were evaluated using spermatozoa functional parameters. A total of 385 infertile couples underwent the procedure of intracytoplasmic sperm injection (ICSI), with an isolated teratozoospermia in the male partner. Semen samples were prepared by using one of the mentioned sperm preparation techniques. The improvements in the percentage of normal mature spermatozoa, rate of fertilization, cleavage, pregnancy and the number of live births were assessed. The normal morphology, spermatozoa DNA fragmentation (SDF) and chromatin maturity checked by using chromomycin A3 (CMA3) with DGC-MACS preparation were better compared to the other three methods. Embryo cleavage, clinical pregnancy and implantation were better improved in the DGC-MACS than in the other tested techniques. The DGC-MACS technique helped in the selection of an increased percentage of normal viable and mature sperm with intact chromatin integrity in patients with teratozoospermia.
Endocannabinoid Degradation Enzyme Inhibitors as Potential Antipsychotics: A Medicinal Chemistry Perspective
Authors: Mangiatordi Giuseppe Felice , Cavalluzzi Maria Maddalena , Delre Pietro , Lamanna Giuseppe , Lumuscio Maria Cristina , Saviano Michele , Majoral Jean-Pierre , Mignani Serge , Duranti Andrea , Lentini Giovanni
Published: February 2023

The endocannabinoid system (ECS) plays a very important role in numerous physiological and pharmacological processes, such as those related to the central nervous system (CNS), including learning, memory, emotional processing, as well pain control, inflammatory and immune response, and as a biomarker in certain psychiatric disorders. Unfortunately, the half-life of the natural ligands responsible for these effects is very short. This perspective describes the potential role of the inhibitors of the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL), which are mainly responsible for the degradation of endogenous ligands in psychic disorders and related pathologies. The examination was carried out considering both the impact that the classical exogenous ligands such as Δ9-tetrahydrocannabinol (THC) and (−)-trans-cannabidiol (CBD) have on the ECS and through an analysis focused on the possibility of predicting the potential toxicity of the inhibitors before they are subjected to clinical studies. In particular, cardiotoxicity (hERG liability), probably the worst early adverse reaction studied during clinical studies focused on acute toxicity, was predicted, and some of the most used and robust metrics available were considered to select which of the analyzed compounds could be repositioned as possible oral antipsychotics.
Diabetic Kidney Disease in Post-Transplant Diabetes Mellitus: Causes, Treatment and Outcomes
Authors: Lim Lee-Moay , Chang Jer-Ming , Kuo Hung-Tien
Published: February 2023

Kidney transplant recipients are a unique subgroup of chronic kidney disease patients due to their single functioning kidney, immunosuppressive agent usage, and long-term complications related to transplantation. Post-transplant diabetes mellitus (PTDM) has a significant adverse effect on renal outcomes in particular. As transplantations enable people to live longer, cardiovascular morbidity and mortality become more prevalent, and PTDM is a key risk factor for these complications. Although PTDM results from similar risk factors to those of type 2 diabetes, the conditions differ in their pathophysiology and clinical features. Transplantation itself is a risk factor for diabetes due to chronic exposure to immunosuppressive agents. Considering current evidence, this article describes the risk factors, pathogenesis, diagnostic criteria, prevention strategies, and management of PTDM. The therapeutic options are discussed regarding their safety and potential drug–drug interactions with immunosuppressive agents.
Potential Haptic Perceptual Dimensionality of Rendered Compliance
Authors: Shao Zhiyu , Li Jingwei , Feng Wanlu , Tang Hongru
Published: February 2023

Studies have proven that humans perceive haptic textures through different perceptual dimensions, such as rough/smooth and soft/hard, which provide useful guidance in the design of haptic devices. However, few of these have focused on the perception of compliance, which is another important perceptual property in haptic interfaces. This research was conducted to investigate the potential basic perceptual dimensions of the rendered compliance and quantify the effects of the simulation parameters. Two perceptual experiments were designed based on 27 stimuli samples generated by a 3-DOF haptic feedback device. Subjects were asked to describe these stimuli using adjectives, classify the samples, and rate them according to corresponding adjective labels. Multi-dimensional scaling (MDS) methods were then used to project adjective ratings into 2D and 3D perception spaces. According to the results, hardness and viscosity are considered two basic perceptual dimensions of the rendered compliance, while crispness can be regarded as a subsidiary perceptual dimension. Then, the relations between simulation parameters and perceptual feelings were analyzed by the regression analysis. This paper may provide a better understanding of the compliance perception mechanism and useful guidance for the improvement of rendering algorithms and devices for haptic human–computer interaction.
Heterogeneous Nucleation in Protein Crystallization
Authors: Liu Hao , Zhao Yue , Sun Jing
Published: February 2023

Protein crystallization was first discovered in the nineteenth century and has been studied for nearly 200 years. Protein crystallization technology has recently been widely used in many fields, such as drug purification and protein structure analysis. The key to successful crystallization of proteins is the nucleation in the protein solution, which can be influenced by many factors, such as the precipitating agent, temperature, solution concentration, pH, etc., among which the role of the precipitating agent is extremely important. In this regard, we summarize the nucleation theory of protein crystallization, including classical nucleation theory, two-step nucleation theory, and heterogeneous nucleation theory. We focus on a variety of efficient heterogeneous nucleating agents and crystallization methods as well. The application of protein crystals in crystallography and biopharmaceutical fields is further discussed. Finally, the bottleneck of protein crystallization and the prospect of future technology development are reviewed.
Quantitative Analysis of Bioluminescence Optical Signal
Authors: Niwa Kazuki , Kubota Hidehiro , Enomoto Toshiteru , Ichino Yoshiro , Ohmiya Yoshihiro
Published: February 2023

Bioluminescence is light emission based on the luciferin–luciferase enzymatic reaction in living organisms. Optical signals from bioluminescence (BL) reactions are available for bioanalysis and bioreporters for gene expression, in vitro, in vivo, and ex vivo bioimaging, immunoassay, and other applications. Although there are numerous bioanalysis methods based on BL signal measurements, the BL signal is measured as a relative value, and not as an absolute value. Recently, some approaches have been established to completely quantify the BL signal, resulting in, for instance, the redetermination of the quantum yield of the BL reaction and counting the photon number of the BL signal at the single-cell level. Reliable and reproducible understanding of biological events in the bioanalysis and bioreporter fields can be achieved by means of standardized absolute optical signal measurements, which is described in an International Organization for Standardization (ISO) document.