bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of Singlet Oxygen Molecule in Pathologies
Authors: Murotomi Kazutoshi , Umeno Aya , Shichiri Mototada , Tanito Masaki , Yoshida Yasukazu
Published: February 2023

Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described.
Natural Killer T-like Cells: Immunobiology and Role in Disease
Authors: Almeida Jani-Sofia , Casanova José Manuel , Santos-Rosa Manuel , Tarazona Raquel , Solana Rafael , Rodrigues-Santos Paulo
Published: February 2023

CD56+ T cells are generally recognized as a distinct population of T cells and are categorized as NKT-like cells. Although our understanding of NKT-like cells is far from satisfactory, it has been shown that aging and a number of disease situations have impacted these cells. To construct an overview of what is currently known, we reviewed the literature on human NKT-like cells. NKT-like cells are highly differentiated T cells with “CD1d-independent” antigen recognition and MHC-unrestricted cell killing. The genesis of NKT-like cells is unclear; however, it is proposed that the acquisition of innate characteristics by T cells could represent a remodeling process leading to successful aging. Additionally, it has been shown that NKT-like cells may play a significant role in several pathological conditions, making it necessary to comprehend whether these cells might function as prognostic markers. The quantification and characterization of these cells might serve as a cutting-edge indicator of individual immune health. Additionally, exploring the mechanisms that can control their killing activity in different contexts may therefore result in innovative therapeutic alternatives in a wide range of disease settings.
Synthesis, In Silico Study, Antibacterial and Antifungal Activities of N-phenylbenzamides
Authors: Sulistyowaty Melanny Ika , Putra Galih Satrio , Budiati Tutuk , Indrianingsih Anastasia Wheni , Anwari Farida , Kesuma Dini , Matsunami Katsuyoshi , Yamauchi Takayasu
Published: February 2023

Antibiotic and antifungal resistance problems have been prevalent in recent decades. One of the efforts to solve the problems is to develop new medicines with more potent antibacterial and antifungal activity. N-phenylbenzamides have the potential to be developed as antibacterial and antifungal medicine. This study aimed to synthesize N-phenylbenzamides and evaluate their in silico and in vitro antibacterial and antifungal activities. The in silico studies conducted absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions along with molecular docking studies. ADMET predictions used pkCSM software online, while the docking studies used MVD software (Molegro ® Virtual Docker version 5.5) on Aminoglycosid-2 ″-phosphotransferase-IIa (APH2 ″-IIa) enzyme with protein data bank (PDB) ID code 3HAV as antibacterial and aspartic proteinases enzyme (Saps) with PDB ID code 2QZX as an antifungal. In vitro, antibacterial and antifungal tests were carried out using the zone of inhibition (ZOI) method. The five N-phenylbenzamides (3a–e) were successfully synthesized with a high yield. Based on in silico and in vitro studies, compounds 3a–e have antibacterial and antifungal activities, where they can inhibit the growth of Gram-positive bacteria (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans. Therefore, compounds 3a–e can be developed as a topical antibacterial and antifungal agent.
Functions of Steroid Hormones in the Male Reproductive Tract as Revealed by Mouse Models
Authors: Walker William H. , Cooke Paul S.
Published: February 2023

Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During the past 30 years, mouse models have been produced in which the expression of genes encoding steroid hormone receptors has been enhanced, partially compromised or eliminated. These mouse models have revealed many of the physiological processes regulated by androgens, estrogens and to a more limited extent glucocorticoids in the testis and male accessory organs. In this review, advances provided by mouse models that have facilitated a better understanding of the molecular regulation of testis and reproductive tract processes by steroid hormones are discussed.
MADS-Box Subfamily Gene GmAP3 from Glycine max Regulates Early Flowering and Flower Development
Authors: Zhang Aijing , He Haobo , Li Yue , Wang Lixue , Liu Yixuan , Luan Xinchao , Wang Jiaxin , Liu Huijing , Liu Shuying , Zhang Jun , Yao Dan
Published: February 2023

AP3 has been studied and is reported to affect structural changes in floral organs in various plants. However, the function of the soybean AP3 genes in flower development is unknown. Here, the full-length cDNA sequence of GmAP3 was obtained by RACE and it was verified that it belongs to the MADS-box subfamily by a bioinformatics analysis. The expression of GmAP3 is closely related to the expression of essential enzyme genes related to flower development. Yeast two-hybrid assays demonstrated that GmAP3 interacts with AP1 to determine the identity of flower organ development. A follow-up analysis showed that overexpression of the GmAP3 gene advanced flowering time and resulted in changes in floral organ morphology. The average flowering time of overexpressed soybean and tobacco plants was 6–8 days earlier than that of wild-type plants, and the average flowering time of gene-edited soybean and tobacco plants was 6–11 days later than that of wild-type plants. In conclusion, GmAP3 may directly or indirectly affect the flower development of soybean. The results of this study lay the foundation for further research on the biological functions of MADS transcriptional factors in soybeans.
Study on New Dental Materials Containing Quinoxaline-Based Photoinitiators in Terms of Exothermicity of the Photopolymerization Process
Authors: Pyszka Ilona , Skowroński Łukasz , Jędrzejewska Beata
Published: February 2023

Modern dentistry places great demands on the dental composites used for filling tooth cavities or treating cavitated tooth decay. The aim of the work was to modify the properties of composites by changing the initiators and co-initiators. This was achieved by using initiators based on a quinoxaline skeleton and co-initiators that are derivatives of acetic acid, which is an advantage of these photoinitiating systems due to the elimination of aromatic amines from the photocurable composition. The composites also differed in dental fillers. The effect of the compounds on the exothermicity of the photopolymerization process, the surface morphology of the obtained materials and the maximum compressive strength were determined. The photoinitiating capacity of the two-component systems was tested by the microcalorimetric method using the multifunctional monomer TMPTA, typical for dental filler compositions. The new photoinitiating systems show particularly good efficiency of free radical polymerization initiation, which occurs by the photoinduced intermolecular electron transfer (PET) mechanism. The comparison of the tested systems with camphorquinone, a photoinitiator traditionally used in dentistry, made it possible to observe a decrease in temperature during photopolymerization without a significant decrease in the polymerization rate or increase in photocuring time, as well as a better homogeneity of the surface of the obtained polymeric materials. This indicates that dye–acetic acid derivative systems may be useful in dental applications.
Extra-Cellular Vesicles Derived from Thyroid Cancer Cells Promote the Epithelial to Mesenchymal Transition (EMT) and the Transfer of Malignant Phenotypes through Immune Mediated Mechanisms
Authors: Mardente Stefania , Aventaggiato Michele , Splendiani Elena , Mari Emanuela , Zicari Alessandra , Catanzaro Giuseppina , Po Agnese , Coppola Lucia , Tafani Marco
Published: February 2023

Thyroid cancer is the most common endocrine cancer, and its incidence is increasing in many countries around the world. Among thyroid cancers, the papillary thyroid cancer (PTC) histotype is particularly prevalent. A small percentage of papillary tumors is associated with metastases and aggressive behavior due to de-differentiation obtained through the epithelial–mesenchymal transition (EMT) by which epithelial thyroid cells acquire a fibroblast-like morphology, reduce cellular adhesion, increase motility and expression of mesenchymal proteins. The tumor microenvironment plays an important role in promoting an aggressive phenotype through hypoxia and the secretion of HMGB1 and other factors. Hypoxia has been shown to drastically change the tumor cell phenotype and has been associated with increasing metastatic and migratory behavior. Cells transfer information to neighboring cells or distant locations by releasing extracellular membrane vesicles (EVs) that contain key molecules, such as mRNAs, microRNAs (miRNAs), and proteins, that are able to modify protein expression in recipient cells. In this study, we investigated the potential role of EVs released by the anaplastic cancer cell line CAL-62 in inducing a malignant phenotype in a papillary cancer cell line (BCPAP).
Tumor Radiosensitization by Gene Electrotransfer-Mediated Double Targeting of Tumor Vasculature
Authors: Savarin Monika , Znidar Katarina , Sersa Gregor , Komel Tilen , Cemazar Maja , Kamensek Urska
Published: February 2023

Targeting the tumor vasculature through specific endothelial cell markers involved in different signaling pathways represents a promising tool for tumor radiosensitization. Two prominent targets are endoglin (CD105), a transforming growth factor β co-receptor, and the melanoma cell adhesion molecule (CD1046), present also on many tumors. In our recent in vitro study, we constructed and evaluated a plasmid for simultaneous silencing of these two targets. In the current study, our aim was to explore the therapeutic potential of gene electrotransfer-mediated delivery of this new plasmid in vivo, and to elucidate the effects of combined therapy with tumor irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice in the syngeneic murine mammary adenocarcinoma tumor model TS/A. Histological analysis of tumors (vascularization, proliferation, hypoxia, necrosis, apoptosis and infiltration of immune cells) was performed to evaluate the therapeutic mechanisms. Additionally, potential activation of the immune response was evaluated by determining the induction of DNA sensor STING and selected pro-inflammatory cytokines using qRT-PCR. The results point to a significant radiosensitization and a good therapeutic potential of this gene therapy approach in an otherwise radioresistant and immunologically cold TS/A tumor model, making it a promising novel treatment modality for a wide range of tumors.
Validation of the Reference Genes for Expression Analysis in the Hippocampus after Transient Ischemia/Reperfusion Injury in Gerbil Brain
Authors: Lewczuk Anita , Boratyńska-Jasińska Anna , Zabłocka Barbara
Published: February 2023

Transient brain ischemia in gerbils is a common model to study the mechanisms of neuronal changes in the hippocampus. In cornu ammonnis 2–3, dentate gyrus (CA2-3,DG) regions of the hippocampus, neurons are resistant to 5-min ischemia/reperfusion (I/R) insult, while cornu ammonnis 1 (CA1) is found to be I/R-vulnerable. The quantitative polymerase chain reaction (qRT-PCR) is widely used to study the expression of genes involved in these phenomena. It requires stable and reliable genes for normalization, which is crucial for comparable and reproducible analyses of expression changes of the genes of interest. The aim of this study was to determine the best housekeeping gene for the I/R gerbil model in two parts of the hippocampus in controls and at 3, 48, and 72 h after recanalization. We selected and tested six reference genes frequently used in central nervous system studies: Gapdh, Actb, 18S rRNA, Hprt1, Hmbs, Ywhaz, and additionally Bud23, using RefFinder, a comprehensive tool based on four commonly used algorithms: delta cycle threshold (Ct), BestKeeper, NormFinder, and geNorm, while Hprt1 and Hmbs were the most stable ones in CA2-3,DG. Hmbs was the most stable in the whole hippocampal formation. This indicates that the general use of Hmbs, especially in combination with Gapdh, a highly expressed reference gene, seems to be suitable for qRT-PCR normalization in all hippocampal regions in this model.
MRPL12 Acts as A Novel Prognostic Biomarker Involved in Immune Cell Infiltration and Tumor Progression of Lung Adenocarcinoma
Authors: Hu Yangyang , Liu Yue , Ma Chenchao , Ai Kaixing
Published: February 2023

Mitochondrial ribosomal protein L7/L12 (MRPL12) is a member of the mitochondrial ribosomal proteins (MRPs). However, the biological function of MRPL12 in lung adenocarcinoma (LUAD) remains unclear. The expression and prognostic value of MRPL12 in LUAD were systematically analyzed using UALCAN, TIMER, HPA, Kaplan–Meier plotter, and GEPIA databases. The relationship between MRPL12 and immune infiltrates was investigated using TIMER and TISIDB databases. The clinical significance of MRPL12 in LUAD patients was validated using a tissue microarray (TMA). Cellular functional experiments were carried out to examine the influences of MRPL12 knockdown on cell proliferation, migration, and invasion. MRPL12 was significantly upregulated in LUAD samples, and high MRPL12 expression was correlated with worse prognosis. MRPL12 expression was markedly associated with immunomodulators, chemokines, and infiltration levels of multiple immune cells. Furthermore, TMA results confirm the upregulation of MRPL12 expression in LUAD, and MRPL12 was identified as an independent prognostic factor in LUAD patients. MRPL12 knockdown inhibited proliferation, migration, and invasion of LUAD cells. These data indicate that MRPL12 is a prognostic biomarker and correlated with immune infiltrates in LUAD. Therefore, MRPL12 shows potential as a therapeutic target for LUAD.
Implicit-Solvent Coarse-Grained Simulations of Linear–Dendritic Block Copolymer Micelles
Authors: Brito Mariano E. , Mikhtaniuk Sofia E. , Neelov Igor M. , Borisov Oleg V. , Holm Christian
Published: February 2023

The design of nanoassemblies can be conveniently achieved by tuning the strength of the hydrophobic interactions of block copolymers in selective solvents. These block copolymer micelles form supramolecular aggregates, which have attracted great attention in the area of drug delivery and imaging in biomedicine due to their easy-to-tune properties and straightforward large-scale production. In the present work, we have investigated the micellization process of linear–dendritic block copolymers in order to elucidate the effect of branching on the micellar properties. We focus on block copolymers formed by linear hydrophobic blocks attached to either dendritic neutral or charged hydrophilic blocks. We have implemented a simple protocol for determining the equilibrium micellar size, which permits the study of linear–dendritic block copolymers in a wide range of block morphologies in an efficient and parallelizable manner. We have explored the impact of different topological and charge properties of the hydrophilic blocks on the equilibrium micellar properties and compared them to predictions from self-consistent field theory and scaling theory. We have found that, at higher degrees of branching in the corona and for short polymer chains, excluded volume interactions strongly influence the micellar aggregation as well as their effective charge.
Effects of Temperature and Salt Stress on the Expression of delta-12 Fatty Acid Desaturase Genes and Fatty Acid Compositions in Safflower
Authors: Li Dandan , Li Kaijie , Zhou Guangchong , He Songtao
Published: February 2023

The regulation of microsomal (e.g., FAD2) and plastidial (e.g., FAD6) oleate desaturases by cold, heat and salt stress were investigated. Gene expression levels and fatty acid compositions were determined in the roots, stems and leaves of safflower following stress treatments. A safflower plastidial oleate desaturase gene, CtFAD6, was cloned, and oleic acid desaturation was confirmed in Synechococcus sp. strain PCC7942. The results showed that temperature regulated oleate desaturation at the transcriptional level, and this regulation pattern was tissue-specific. CtFAD2-1, CtFAD2-2 and CtFAD6 were significantly induced under cold and heat stress in young leaves, and CtFAD2-2 and CtFAD6 were slightly induced in young stems. In contrast, CtFAD2-1, CtFAD2-11 and CtFAD2-10 were sensitive to salt stress in all safflower tissues (roots, stem and leaves). CtFAD6 was insensitive to salt and was slightly induced in leaves only.
1H-NMR Karplus Analysis of Molecular Conformations of Glycerol under Different Solvent Conditions: A Consistent Rotational Isomerism in the Backbone Governed by Glycerol/Water Interactions
Authors: Nishida Yoshihiro , Aono Reina , Dohi Hirofumi , Ding Wuxiao , Uzawa Hirotaka
Published: February 2023

Glycerol is a symmetrical, small biomolecule with high flexibility in molecular conformations. Using a 1H-NMR spectroscopic Karplus analysis in our way, we analyzed a rotational isomerism in the glycero backbone which generates three kinds of staggered conformers, namely gt (gauche-trans), gg (gauche-gauche), and tg (trans-gauche), at each of sn-1,2 and sn-2,3 positions. The Karplus analysis has disclosed that the three rotamers are consistently equilibrated in water keeping the relation of ‘gt:gg:tg = 50:30:20 (%)’ at a wide range of concentrations (5 mM~540 mM). The observed relation means that glycerol in water favors those symmetric conformers placing 1,2,3-triol groups in a gauche/gauche geometry. We have found also that the rotational isomerism is remarkably changed when the solvent is replaced with DMSO-d6 or dimethylformamide (DMF-d7). In these solvents, glycerol gives a relation of ‘gt:gg:tg = 40:30:30 (%)’, which means that a remarkable shift occurs in the equilibrium between gt and tg conformers. By this shift, glycerol turns to also take non-symmetric conformers orienting one of the two vicinal diols in an antiperiplanar geometry.
Protective Effects of PEP-1-GSTA2 Protein in Hippocampal Neuronal Cell Damage Induced by Oxidative Stress
Authors: Choi Yeon Joo , Shin Min Jea , Youn Gi Soo , Park Jung Hwan , Yeo Hyeon Ji , Yeo Eun Ji , Kwon Hyun Jung , Lee Lee Re , Kim Na Yeon , Kwon Su Yeon , Jung Hyo Young , Cho Yong-Jun , Kim Dae Won , Park Jinseu , Han Kyu Hyung , Lee Keun Wook , Park Jong Kook , Lee Chan Hee , Eum Won Sik , Choi Soo Young
Published: February 2023

Glutathione S-transferase alpha 2 (GSTA2), a member of the glutathione S-transferase family, plays the role of cellular detoxification against oxidative stress. Although oxidative stress is related to ischemic injury, the role of GSTA2 against ischemia has not been elucidated. Thus, we studied whether GSTA2 prevents ischemic injury by using the PEP-1-GSTA2 protein which has a cell-permeable protein transduction domain. We revealed that cell-permeable PEP-1-GSTA2 transduced into HT-22 cells and markedly protected cell death via the inhibition of reactive oxygen species (ROS) production and DNA damage induced by oxidative stress. Additionally, transduced PEP-1-GSTA2 promoted mitogen-activated protein kinase (MAPK), and nuclear factor-kappaB (NF-κB) activation. Furthermore, PEP-1-GSTA2 regulated Bcl-2, Bax, cleaved Caspase-3 and -9 expression protein levels. An in vivo ischemic animal model, PEP-1-GSTA2, markedly prevented the loss of hippocampal neurons and reduced the activation of microglia and astrocytes. These findings indicate that PEP-1-GSTA2 suppresses hippocampal cell death by regulating the MAPK and apoptotic signaling pathways. Therefore, we suggest that PEP-1-GSTA2 will help to develop the therapies for oxidative-stress-induced ischemic injury.
Mineral and Phytic Acid Content as Well as Phytase Activity in Flours and Breads Made from Different Wheat Species
Authors: Longin C. Friedrich. H. , Afzal Muhammad , Pfannstiel Jens , Bertsche Ute , Melzer Tanja , Ruf Andrea , Heger Christoph , Pfaff Tobias , Schollenberger Margit , Rodehutscord Markus
Published: February 2023

Wheat is of high importance for a healthy and sustainable diet for the growing world population, partly due to its high mineral content. However, several minerals are bound in a phytate complex in the grain and unavailable to humans. We performed a series of trials to compare the contents of minerals and phytic acid as well as phytase activity in several varieties from alternative wheat species spelt, emmer and einkorn with common wheat. Additionally, we investigated the potential of recent popular bread making recipes in German bakeries to reduce phytic acid content, and thus increase mineral bioavailability in bread. For all studied ingredients, we found considerable variance both between varieties within a species and across wheat species. For example, whole grain flours, particularly from emmer and einkorn, appear to have higher mineral content than common wheat, but also a higher phytic acid content with similar phytase activity. Bread making recipes had a greater effect on phytic acid content in the final bread than the choice of species for whole grain flour production. Recipes with long yeast proofing or sourdough and the use of whole grain rye flour in a mixed wheat bread minimized the phytic acid content in the bread. Consequently, optimizing food to better nourish a growing world requires close collaboration between research organizations and practical stakeholders ensuring a streamlined sustainable process from farm to fork.
Association between an Increased Serum CCL5 Level and Pathophysiology of Degenerative Joint Disease in the Temporomandibular Joint in Females
Authors: Watanabe Haruhisa , Iori Takashi , Lee Ji-Won , Kajii Takashi S. , Takakura Aya , Takao-Kawabata Ryoko , Kitagawa Yoshimasa , Maruoka Yutaka , Iimura Tadahiro
Published: February 2023

Degenerative joint disease of the temporomandibular joints (DJD-TMJ) clinically manifests with symptoms such as orofacial pain, joint sounds and limited jaw movements. Our research group previously reported the functional necessity of a chemokine-chemokine receptor axis of CCL5-CCR5 in osteoclasts. Accumulated studies reported that this axis was involved in the pathogenesis of bone and joint destructive diseases, suggesting CCL5 as a potent biomarker. This study investigated whether or not the serum level of CCL5 can be a biomarker of DJD-TMJ and concomitantly analyzed changes in the serum and urine levels of bone markers to see whether or not changes in the rate of bone metabolism were predisposing. We enrolled 17 female subjects with diagnosed DJD-TMJ and sexually and age-matched 17 controls. The serum CCL5 level in DJD-TMJ subjects was significantly higher than that in the control subjects. Multivariate analyses indicated an association between an augmented CCL5 level and the rate of bone metabolism, especially in relatively young DJD-TMJ subjects without other systemic symptoms. A principal component analysis of serum markers and our pharmacological experiment using a postmenopausal model of ovariectomized rats suggested that an augmented serum CCL5 level specifically reflected DJD-TMJ and that covert changes in the rate of bone metabolism predisposed individuals to DJD-TMJ.
Deciphering the Tubulin Language: Molecular Determinants and Readout Mechanisms of the Tubulin Code in Neurons
Authors: Zocchi Riccardo , Compagnucci Claudia , Bertini Enrico , Sferra Antonella
Published: February 2023

Microtubules (MTs) are dynamic components of the cell cytoskeleton involved in several cellular functions, such as structural support, migration and intracellular trafficking. Despite their high similarity, MTs have functional heterogeneity that is generated by the incorporation into the MT lattice of different tubulin gene products and by their post-translational modifications (PTMs). Such regulations, besides modulating the tubulin composition of MTs, create on their surface a “biochemical code” that is translated, through the action of protein effectors, into specific MT-based functions. This code, known as “tubulin code”, plays an important role in neuronal cells, whose highly specialized morphologies and activities depend on the correct functioning of the MT cytoskeleton and on its interplay with a myriad of MT-interacting proteins. In recent years, a growing number of mutations in genes encoding for tubulins, MT-interacting proteins and enzymes that post-translationally modify MTs, which are the main players of the tubulin code, have been linked to neurodegenerative processes or abnormalities in neural migration, differentiation and connectivity. Nevertheless, the exact molecular mechanisms through which the cell writes and, downstream, MT-interacting proteins decipher the tubulin code are still largely uncharted. The purpose of this review is to describe the molecular determinants and the readout mechanisms of the tubulin code, and briefly elucidate how they coordinate MT behavior during critical neuronal events, such as neuron migration, maturation and axonal transport.
Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept
Authors: Shushunova Natalia A. , Mayorova Oksana A. , Prikhozhdenko Ekaterina S. , Goryacheva Olga A. , Kulikov Oleg A. , Plastun Valentina O. , Gusliakova Olga I. , Muslimov Albert R. , Inozemtseva Olga A. , Pyataev Nikolay A. , Shirokov Alexander A. , Gorin Dmitry A. , Sukhorukov Gleb B. , Sindeeva Olga A.
Published: February 2023

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.
SOCS7-Derived BC-Box Motif Peptide Mediated Cholinergic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells
Authors: Kanno Hiroshi , Matsumoto Shutaro , Yoshizumi Tetsuya , Nakahara Kimihiro , Shinonaga Masamichi , Kubo Atsuhiko , Fujii Satoshi , Ishizuka Yasuyuki , Tanaka Masaki , Ichihashi Masamitsu , Murata Hidetoshi
Published: February 2023

Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide. Here, we report that ADMSCs differentiate to the cholinergic phenotype of neurons by the SOCS7-derived BC-box motif peptide. At operations for patients with neurological disorders, a small amount of subcutaneous fat was obtained. Two weeks later, adipose-derived mesenchymal stem cells (ADMSCs) were isolated and cultured for a further 1 to 2 weeks. Flow cytometry analysis for characterization of ADMSCs was performed with CD73, CD90, and CD105 as positive markers, and CD14, CD31, and CD56 as negative markers. The results showed that cultured cells were compatible with ADMSCs. Immunocytochemical studies showed naïve ADMSCs immunopositive for p75NTR, RET, nestin, keratin, neurofilament-M, and smooth muscle actin. ADMSCs were suggested to be pluripotent stem cells. A peptide corresponding to the amino-acid sequence of BC-box motif derived from SOCS7 protein was added to the medium at a concentration of 2 μM. Three days later, immunocytochemistry analysis, Western blot analysis, ubiquitination assay, and electrophysiological analysis with patch cramp were performed. Immunostaining revealed the expression of neurofilament H (NFH), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). In addition, Western blot analysis showed an increase in the expression of NFH, ChAT, and TH, and the expression of ChAT was more distinct than TH. Immunoprecipitation with JAK2 showed an increase in the expression of ubiquitin. Electrophysiological analysis showed a large holding potential at the recorded cells through path electrodes. The BC-box motif peptide derived from SOCS7 promoted the cholinergic differentiation of ADMSCs. This novel method will contribute to research as well as regenerative medicine for cholinergic neuron diseases.
Pupal Age Estimation of Sarcophaga peregrina (Diptera: Sarcophagidae) at Different Constant Temperatures Utilizing ATR-FTIR Spectroscopy and Cuticular Hydrocarbons
Authors: Shang Yanjie , Feng Yakai , Ren Lipin , Zhang Xiangyan , Yang Fengqin , Zhang Changquan , Guo Yadong
Published: February 2023

Sarcophaga peregrina (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae) is a forensically important flesh fly that has potential value in estimating the PMImin. The precise pupal age estimation has great implications for PMImin estimation. During larval development, the age determination is straightforward by the morphological changes and variation of length and weight, however, the pupal age estimation is more difficult due to anatomical and morphological changes not being visible. Thus, it is necessary to find new techniques and methods that can be implemented by standard experiments for accurate pupal age estimation. In this study, we first investigated the potential of attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and cuticular hydrocarbons (CHCs) for the age estimations of S. peregrina pupae at different constant temperatures (20 °C, 25 °C, and 30 °C). The orthogonal projections latent structure discrimination analysis (OPLS-DA) classification model was used to distinguish the pupae samples of different developmental ages. Then, a multivariate statistical regression model, partial least squares (PLS), was established with the spectroscopic and hydrocarbon data for pupal age estimations. We identified 37 CHCs with a carbon chain length between 11 and 35 in the pupae of S. peregrina. The results of the OPLS-DA model show a significant separation between different developmental ages of pupae (R2X > 0.928, R2Y > 0.899, Q2 > 0.863). The PLS model had a satisfactory prediction with a good fit between the actual and predicted ages of the pupae (R2 > 0.927, RMSECV < 1.268). The results demonstrate that the variation tendencies of spectroscopy and hydrocarbons were time-dependent, and ATR-FTIR and CHCs may be optimal for the age estimations of pupae of forensically important flies with implications for PMImin estimation in forensic practice.
Spectral Dual-Layer Computed Tomography Can Predict the Invasiveness of Ground-Glass Nodules: A Diagnostic Model Combined with Thymidine Kinase-1
Authors: Wang Tong , Yue Yong , Fan Zheng , Jia Zheng , Yu Xiuze , Liu Chen , Hou Yang
Published: February 2023

Objectives: Few studies have explored the use of spectral dual-layer detector-based computed tomography (SDCT) parameters, thymidine kinase-1 (TK1), and tumor abnormal protein (TAP) for the detection of ground-glass nodules (GGNs). Therefore, we aimed to evaluate the quantitative and qualitative parameters generated from SDCT for predicting the pathological subtypes of GGN-featured lung adenocarcinoma combined with TK1 and TAP. Material and Methods: Between July 2021 and September 2022, 238 patients with GGNs were retrospectively enrolled in this study. SDCT and tests for TK1 and TAP were performed preoperatively, and the lesions were divided into glandular precursor lesions (PGL), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC), according to the pathological results. A receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of these parameters. Multivariate logistic regression analysis was performed to construct a joint diagnostic model and create a nomogram. Results: This study included 238 GGNs, including 41 atypical adenomatous hyperplasias (AAH), 62 adenocarcinomas in situ (AIS), 49 MIA, and 86 IAC, with a high proportion of women, non-smokers, and pure ground-glass nodule (pGGN). CT100 keV (a/v), electronic density (EDW) (a/v), Daverage, Dsolid, TK1, and TAP of MIA and IAC were higher than those of PGL. The effective atomic number (Zeff (a/v)) was lower in MIA and IAC than in PGL (all p < 0.05). Logistic regression analysis showed that Zeff (a), EDW (a), TK1, Daverage, and internal bronchial morphology were crucial factors in predicting the aggressiveness of GGN. Zeff (a) had the highest diagnostic performance with an area under the ROC curve (AUC) = 0.896, followed by EDW (a) (AUC = 0.838) and CT100 keVa (AUC = 0.819). The diagnostic model and nomogram constructed using these five parameters (Zeff (a) + EDW (a) + CT100 keVa + Daverage + TK1) had an AUC = 0.933, which was higher than the individual parameters (p < 0.05). Conclusions: Multiple quantitative and functional parameters can be selected based on SDCT, especially Zeff (a) and EDW (a), which have high sensitivity and specificity for predicting GGNs’ invasiveness. Additionally, the combination of TK1 can further improve diagnostic performance, and using a nomogram is helpful for individualized predictions.
Controls of Central and Peripheral Blood Pressure and Hemorrhagic/Hypovolemic Shock
Authors: Ranjan Amaresh K. , Gulati Anil
Published: February 2023

The pressure exerted on the heart and blood vessels because of blood flow is considered an essential parameter for cardiovascular function. It determines sufficient blood perfusion, and transportation of nutrition, oxygen, and other essential factors to every organ. Pressure in the primary arteries near the heart and the brain is known as central blood pressure (CBP), while that in the peripheral arteries is known as peripheral blood pressure (PBP). Usually, CBP and PBP are correlated; however, various types of shocks and cardiovascular disorders interfere with their regulation and differently affect the blood flow in vital and accessory organs. Therefore, understanding blood pressure in normal and disease conditions is essential for managing shock-related cardiovascular implications and improving treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic, and cellular) of blood pressure and their regulation in hemorrhagic/hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.
Ultrasonography Measurement of Renal Dimension and Its Correlation with Age, Body Indices, and eGFR in Type 1 Diabetes Mellitus Patients: Real World Data in Taiwan
Authors: Su Hsuan-An , Chen Jung-Fu , Fu Chung-Ming , Lee Yueh-Ting , Wang Yi , Huang Chiang-Chi , Chen Jin-Bor , Lee Chien-Te , Wu Chien-Hsing
Published: February 2023

Background: Assessment of renal size is clinically significant for the screening, diagnosis, and follow-up of renal diseases as the basis of clinical decisions. However, the relationship of renal dimension with age, body indices, and the estimated glomerular filtration rate (eGFR) has rarely been reported in the Chinese type 1 diabetes mellitus (T1DM) population. Methods: A total of 220 T1DM patients were retrospectively analyzed from the Chang Gung Research Database in Taiwan. Demographic data, laboratory data, and ultrasonographic images from January 2001 to November 2018 were extracted. Results: Eighty-five participants (38.6%) were male. The mean age was 34.2 years. The median eGFR was 60.0 mL/min/1.73 m2. The mean ultrasonographic left and right renal lengths (LL and RL) with S.D. were 10.9 ± 1.5 cm and 11.0 ± 1.1 cm, respectively. Renal lengths were longer with increasing body height and body weight but shorter with increasing age in patients with T1DM. In trajectory analysis, a linear mixed model revealed no significant trend in the changes in eGFR during the follow-up period. Moreover, renal length did not play a significant role in predicting KDIGO CKD stage 5 in the cohort. Conclusions: Renal length and its comparison to the reference ranges demonstrated very limited advantages in predicting renal function decline in T1DM patients.
Female Sexual Dysfunction in Association with Sexual History, Sexual Abuse and Satisfaction: A Cross-Sectional Study in Hungary
Authors: Erdős Csaba , Kelemen Oguz , Pócs Dávid , Horváth Edina , Dudás Nóra , Papp András , Paulik Edit
Published: February 2023

Female sexual dysfunction (FSD) has a negative impact on women’s quality of life, self-esteem, and physical health. The aim of the present study was to explore the prevalence and the factors associated with FSD using an online questionnaire. A cross-sectional survey was conducted among young adults (18−35 years old) in Hungary using the DSM-5 criteria. The participants (n = 5942) were divided into three major groups: FSD (20.3%), an intermediate group (43.9%), and a control group (35.6%). Most of the women showing FSD were affected with female orgasmic disorder (9.2%) and genito-pelvic pain/penetration disorder (4.6%), while female sexual interest/arousal disorder was found in altogether 100 women (1.7%); 4.8% of women were affected by more than one definite disorder. The occurrence of female sexual dysfunction was related to the women’s previous sexual history (first sexual experience, sexual education, early encounter with pornographic content, and sexual abuse), their self-satisfaction (with their own body, genitalia, and sexual attraction), and their sexual orientation. Sexual dysfunction showed a strong association with abuse, sexually transmitted diseases, and self-esteem. The present study identified the relationship between sexual dysfunctions and other health conditions, which can be the basis for some form of screening and early assistance programs for FSD.
Study of the Thyroid Profile of Patients with Alopecia
Authors: Popa Adelina , Carsote Mara , Cretoiu Dragos , Dumitrascu Mihai Cristian , Nistor Claudiu-Eduard , Sandru Florica
Published: February 2023

Thyroid hormones are required for the physiological growth and maintenance of hair follicles. We aim to study the thyroid profile of patients with alopecia. This is a narrative review. PubMed literature was searched from 2013 to 2022. We followed different types of alopecia: alopecia areata (AA), androgenic alopecia in males and females, telogen effluvium (TE), frontal fibrosing alopecia (FFA), lichen planopilaris, and alopecia neoplastica (AN). AA shares a common autoimmune background with autoimmune thyroid diseases, either sporadic or belonging to autoimmune polyglandular syndromes. Some data suggested that AA is more severe if thyroid anomalies are confirmed, including subclinical dysfunction or positive antithyroid antibodies with normal hormone values. However, routine thyroid screening for patients with AA, if the patients are asymptomatic from a thyroid point of view and they have negative personal and family history of autoimmunity, remains controversial. TE, apart from the autoimmune type, associates thyroid anomalies of a hormonal assay (between 5.7% and 17%). FFA, mostly a postmenopausal entity (however, not exclusive), associates a higher prevalence of thyroid conditions (up to 50%) than the general population. However, these might have an age-dependent pattern, thus the association may be incidental since there are a limited number of studies. Overall, alopecia remains a very challenging condition for patients and physicians; a multidisciplinary team is required to improve the outcome and quality of life. The common autoimmune background is suggestive of some types of alopecia and thyroid disorders, yet, the underlying mechanisms are still a matter of debate. AA, TE, FFA, LPP, and, potentially, female pattern hair loss have been found to be connected with thyroid entities, thus a state of awareness from a dual perspective, of trichology and endocrinology, is helpful.
The Influence of Sex on Characteristics and Outcomes of Coronavirus-19 Patients: A Retrospective Cohort Study
Authors: Lee Song-I , Chung Chaeuk , Park Dongil , Kang Da Hyun , Ju Ye-Rin , Lee Jeong Eun
Published: February 2023

Background: The influence of sex on the clinical characteristics and prognosis of coronavirus disease (COVID-19) patients is variable. This study aimed to evaluate COVID-19 management based on sex differences. Methods: We retrospectively reviewed COVID-19 patients who were admitted to the tertiary hospital between January 2020 and March 2021. Logistic regression analysis was used to evaluate the factors associated with in-hospital mortality. Results: During the study period, 584 patients were admitted to our hospital. Among them, 305 patients (52.2%) were female, and 279 patients (47.8%) were male. Males were younger than females, and frailty scale was lower in males than in females. Fever was more common in males, and there was no difference in other initial symptoms. Among the underlying comorbidities, chronic obstructive disease was more common in males, and there were no significant differences in other comorbidities. Moreover, treatment, severity, and outcome did not significantly differ between the groups. The risk factors for in-hospital mortality were age, high white blood cell count, and c-reactive protein level. Conclusions: We found no definite sex differences in the clinical characteristics and outcomes of COVID-19 patients. However, a better understanding of sex-dependent differences in COVID-19 patients could help in understanding and treating patients.
Could Temperamental Features Modulate Participation in Clinical Trials?
Authors: Cintoli Simona , Elefante Camilla , Radicchi Claudia , Brancati Giulio Emilio , Bacciardi Silvia , Bonaccorsi Joyce , Siciliano Gabriele , Maremmani Icro , Perugi Giulio , Tognoni Gloria
Published: February 2023

The prodromal stages of Alzheimer’s disease (AD) are the primary focus of research aimed at slowing disease progression. This study explores the influence of affective temperament on the motivation of people with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) to participate in clinical trials. One hundred four subjects with MCI and SCD were screened for participation in pharmacological and non-pharmacological trials. Affective temperament was assessed based on the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego (TEMPS) scale. Demographic variables and temperament subscales scores were compared between MCI and SCD patients and among patients participating in the pharmacological trial, the non-pharmacological trial and refusing participation. Twenty-one subjects consented to participate in the pharmacological trial, seventy consented to the non-pharmacological trial and thirteen refused to participate in any trial. Patients with SCD had greater education and more depressive temperamental traits than those with MCI. While older age, higher education and anxious temperament were negatively associated with participation in the pharmacological trial, irritable temperamental positively predicted pharmacological trial participation. In conclusion, temperamental features may affect the willingness of patients with MCI and SCD to take part in clinical trials and, especially, the choice to participate in pharmacological studies.
Towards Optimum Mandibular Reconstruction for Dental Occlusal Rehabilitation: From Preoperative Virtual Surgery to Autogenous Particulate Cancellous Bone and Marrow Graft with Custom-Made Titanium Mesh—A Retrospective Study
Authors: Onodera Kei , Miyamoto Ikuya , Hoshi Isao , Kawamata Shinsuke , Takahashi Noriaki , Shimazaki Nobuko , Kondo Hisatomo , Yamada Hiroyuki
Published: February 2023

The purpose of this retrospective study was to evaluate computer-assisted virtual surgery and the outcomes of mandibular reconstruction using an autogenous particulate cancellous bone and marrow (PCBM) graft combined with a custom-made titanium mesh (TiMesh) using a three-dimensional (3D) printing model. Eighteen consecutive patients were included, and preoperative virtual simulation surgery was performed using digital data. Segmental bone defects showed deviation of the mandible due to displacement of the condyle and segments, unnatural length of the mandibular body, or poorer intermaxillary relationship compared to the marginal bone defect caused by previous operations. These mandibular disharmonies could be simulated, and virtual surgery was performed on a computer with adjustment of displaced mandibular segments, length of the mandibular body, and dental arch with digital bone augmentation. TiMesh was manually pre-bent using a 3D printing model, and PCBM from the iliac crest was grafted with TiMesh. The short-term clinical results were good; reconstruction of the alveolar crest was prosthetically desirable; and minor complications were observed. In conclusion, virtual reconstruction is crucial for treating complex deviated mandibles. Accurate condylar and dental arch positions with an optimum mandibular length are important for prosthetically satisfactory mandibular reconstruction.