bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Usefulness of Interleukin-8 as a Biomarker of Inflammation and Metabolic Dysregulation in Dairy Cows
Authors: Puppel Kamila , Slósarz Jan , Solarczyk Paweł , Grodkowski Grzegorz , Kostusiak Piotr , Kalińska Aleksandra , Balcerak Marek , Kunowska-Slósarz Małgorzata , Gołębiewski Marcin
Published: October 2024

The study aimed to evaluate interleukin-8 (IL-8) as a biomarker for udder inflammation in dairy cows and to explore its associations with various metabolic parameters indicative of systemic inflammation and metabolic dysregulation. Dairy cows (multiparous) were categorized into five somatic cell count (SCC) classes: Class I (<100,000 cells/mL; n = 45), Class II (100,000–200,000 cells/mL; n = 62), Class III (201,000–400,000 cells/mL; n = 52), Class IV (401,000–1,000,000 cells/mL; n = 73), and Class V (>1,000,000 cells/mL; n = 56). The study quantified IL-8 levels and analyzed their correlations with NEFAs (non-esterified fatty acids), BHBA (beta-hydroxybutyrate), GGTP (gamma-glutamyltransferase), and AspAT (aspartate aminotransferase). IL-8 concentrations demonstrated a significant and progressive increase across the SCC classes, establishing a strong positive correlation with SCC (p < 0.01). Additionally, IL-8 levels exhibited positive correlations with GGTP (p < 0.01) and AspAT (p < 0.01), indicating that elevated IL-8 is associated with increased hepatic enzyme activities and potential liver dysfunction. Furthermore, IL-8 showed significant positive correlations with NEFAs (p < 0.01) and BHBA (p < 0.05), linking higher IL-8 levels to metabolic disturbances such as ketosis and negative energy balance. Variations in metabolic parameters, including NEFAs, BHBA, GGTP, and AspAT, across the SCC classes underscored the association between elevated SCC levels and metabolic dysregulation in dairy cows. These findings highlight the interrelated nature of the inflammatory responses and metabolic disturbances in dairy cattle, emphasizing that an elevated SCC not only signifies udder inflammation but also correlates with systemic metabolic alterations indicative of ketosis and liver damage.
Analyzing Amylin Aggregation Inhibition Through Quantum Dot Fluorescence Imaging
Authors: Yin Xiaoyu , Liu Ziwei , Huanood Gegentuya , Sawatari Hayate , Shimamori Keiya , Kuragano Masahiro , Tokuraku Kiyotaka
Published: October 2024

Protein aggregation is associated with various diseases caused by protein misfolding. Among them, amylin deposition is a prominent feature of type 2 diabetes. At present, the mechanism of amylin aggregation remains unclear, and this has hindered the treatment of type 2 diabetes. In this study, we analyzed the aggregation process of amylin using the quantum dot (QD) imaging method. QD fluorescence imaging revealed that in the presence of 100 μM amylin, aggregates appeared after 12 h of incubation, while a large number of aggregates formed after 24 h of incubation, with a standard deviation (SD) value of 5.435. In contrast, 50 μM amylin did not induce the formation of aggregates after 12 h of incubation, although a large number of aggregates were observed after 24 h of incubation, with an SD value of 2.883. Confocal laser microscopy observations revealed that these aggregates were deposited in three dimensions. Transmission electron microscopy revealed that amylin existed as misfolded fibrils in vitro and that QDs were uniformly bound to the amylin fibrils. In addition, using a microliter-scale high-throughput screening (MSHTS) system, we found that rosmarinic acid, a polyphenol, inhibited amylin aggregation at a half-maximal effective concentration of 852.8 μM. These results demonstrate that the MSHTS system is a powerful tool for evaluating the inhibitory activity of amylin aggregation. Our findings will contribute to the understanding of the pathogenesis of amylin-related diseases and the discovery of compounds that may be useful in the treatment and prevention of these diseases.
Tegaserod Stimulates 5-HT4 Serotonin Receptors in the Isolated Human Atrium
Authors: Hesse Christin , Neumann Joachim , Compan Valerie , Ponimaskin Evgeni , Müller Franziska E. , Hofmann Britt , Gergs Ulrich
Published: October 2024

Tegaserod (1-{[(5-methoxy-1H-indol-3-yl)methyliden]amino}-3-pentylguanidine) is a potent agonist at human recombinant 5-HT4 serotonin receptors. Consequently, tegaserod is utilized in the treatment of bowel diseases. The objective of this study was to test the hypothesis that tegaserod stimulates human cardiac atrial 5-HT4-receptors via cyclic adenosine monophosphate (cAMP)-dependent pathways. Tegaserod exerted positive inotropic effects (PIEs) and positive chronotropic effects (PCEs) in isolated left and right atrial preparations, respectively, from mice with cardiac-specific overexpression of the human 5-HT4 serotonin receptor (5-HT4-TG) in a concentration- and time-dependent manner. However, no effect was observed in the hearts of littermates of wild-type mice (WT). Western blot analysis revealed that the expression of 5-HT4 receptors was significantly higher in 5-HT4-TG mice compared to WT mice. The specificity of the signal for the 5-HT4 receptor was confirmed by the absence of the signal in the hearts of 5-HT4 receptor knockout mice. Furthermore, tegaserod increased the force of contraction (at concentrations as low as 10 nM), reduced the time of tension relaxation, and increased the rate of tension development in isolated electrically stimulated (at a rate of 60 beats per minute) human right atrial preparations (HAPs, obtained during open-heart surgery) when administered alone. The potency and efficacy of tegaserod to raise the force of contraction were enhanced in the presence of cilostamide, a phosphodiesterase III inhibitor. The positive inotropic effect of tegaserod in HAPs was found to be attenuated by the 5-HT4 serotonin receptor antagonist GR 125487 (0.1 µM). The efficacy of tegaserod (10 µM) in raising the force of contraction in HAPs was less pronounced than that of serotonin (10 µM) or isoprenaline (1 µM). Tegaserod shifted the concentration–response curve of the force of contraction to serotonin to the right in HAPs, indicating that it is a partial agonist at 5-HT4 serotonin receptors in this model. We propose that the mechanism of action of tegaserod in HAPs involves cAMP-dependent phosphorylation of cardiac regulatory proteins.
Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization
Authors: Lee Hyokyoung , Park Sung-Kyun , Lim Junghyun
Published: October 2024

Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies.
Thermal Conductivity Enhancement of Doped Magnesium Hydroxide for Medium-Temperature Heat Storage: A Molecular Dynamics Approach and Experimental Validation
Authors: Kur Anti , Darkwa Jo , Worall Mark , Calautit John , Boukhanouf Rabah
Published: October 2024

Magnesium hydroxide, Mg(OH)2, is recognized as a promising material for medium-temperature heat storage, but its low thermal conductivity limits its full potential application. In this study, thermal enhancement of a developed magnesium hydroxide-potassium nitrate (Mg(OH)2-KNO3) material was carried out with aluminum oxide (Al2O3) nanomaterials. The theoretical results obtained through a molecular dynamics (MD) simulation approach showed an enhancement of about 12.9% in thermal conductivity with an optimal 15 wt% of Al2O3. There was also close agreement with the experimental results within an error of ≤10%, thus confirming the reliability of the theoretical approach and the potential of the developed Mg(OH)2-KNO3 as a medium heat storage material. Further investigation is, however, encouraged to establish the long-term recyclability of the material towards achieving a more efficient energy storage process.
Transcriptomic Analysis During Olive Fruit Development and Expression Profiling of Fatty Acid Desaturase Genes
Authors: Serrano Alicia , García-Martín Judith , Moret Martín , Martínez-Rivas José Manuel , Luque Francisco
Published: October 2024

The olive fruit is a drupe whose development and ripening takes several months from flowering to full maturation. During this period, several biochemical and physiological changes occur that affect the skin color, texture, composition, and size of the mesocarp. The final result is a fruit rich in fatty acids, phenolic compounds, tocopherols, pigments, sterols, terpenoids, and other compounds of nutritional interest. In this work, a transcriptomic analysis was performed using flowers (T0) and mesocarp tissue at seven different stages during olive fruit development and ripening (T1–T7) of the ‘Picual’ cultivar. A total of 1755 genes overexpressed at any time with respect to the flowering stage were further analyzed. These genes were grouped into eight clusters based on their expression profile. The gene enrichment analysis revealed the most relevant biological process of every cluster. Highlighting the important role of hormones at very early stages of fruit development (T1, Cluster 1), whereas genes involved in fatty acid biosynthesis were relevant throughout the fruit developmental process. Hence, genes coding for different fatty acid desaturase (SAD, FAD2, FAD3, FAD4, FAD5, FAD6, and FAD7) enzymes received special attention. In particular, 26 genes coding for different fatty acid desaturase enzymes were identified in the ‘Picual’ genome, contributing to the improvement of the genome annotation. The expression pattern of these genes during fruit development corroborated their role in determining fatty acid composition.
Alpha- to Beta-Cell Transdifferentiation in Neonatal Compared with Adult Mouse Pancreas in Response to a Modest Reduction in Beta-Cells Using Streptozotocin
Authors: Hahm Jiwon , Thirunavukarasu Bavina , Gadoo Reva , Andrade Juan Andres Fernandez , Dalton Tyler , Arany Edith , Hill David J.
Published: October 2024

Following the near-total depletion of pancreatic beta-cells with streptozotocin (STZ), a partial recovery of beta-cell mass (BCM) can occur, in part due to the alpha- to beta-cell transdifferentiation with an intermediary insulin/glucagon bi-hormonal cell phenotype. However, human type 2 diabetes typically involves only a partial reduction in BCM and it is not known if recovery after therapeutic intervention involves islet cell transdifferentiation, or how this varies with age. Here, we used transgenic mouse models to examine if islet cell transdifferentiation contributes to BCM recovery following only a partial depletion of BCM. Cell lineage tracing was employed using Glucagon-Cre/yellow fluorescent protein (YFP) transgenic mice treated with STZ (25 mg/kg—neonates; 70 mg/kg—adults) or vehicle alone on 3 consecutive days. Mice were euthanized 2–30 days later with a prior glucose tolerance test on day 30, and immunofluorescence histology performed on the pancreata. Beta-cell abundance was reduced by 30–40% two days post STZ in both neonates and adults, and subsequently partially recovered in adult but not neonatal mice. Glucose tolerance recovered in adult females, but not in males or neonates. Bi-hormonal cell abundance increased 2–3-fold in STZ-treated mice vs. controls in both neonates and adults, as did transdifferentiated cells expressing insulin and the YFP lineage tag, but not glucagon. Transdifferentiated cell presence was an order of magnitude lower than that of bi-hormonal cells. We conclude that alpha- to beta-cell transdifferentiation occurs in mice following only a moderate depletion in BCM, and that this was accompanied by a partial recovery of BCM in adults.
Relationship Between Serum Uromodulin as a Marker of Kidney Damage and Metabolic Status in Patients with Chronic Kidney Disease of Non-Diabetic Etiology
Authors: Žeravica Radmila , Ilinčić Branislava , Burić Dragan , Jakovljević Ana , Crnobrnja Veljko , Ilić Dalibor , Papuga Marija Vukmirović
Published: October 2024

Chronic kidney disease (CKD) is often associated with dyslipidemia, marked by lipid abnormalities that can worsen kidney function and increase cardiovascular risk. A promising biomarker for evaluating kidney function and metabolic status in chronic kidney disease (CKD) is serum uromodulin (sUmod). This study sought to further investigate the relationship between sUmod levels and metabolic status in non-diabetic CKD patients. A sensitive ELISA method was used to determine sUmod levels in 90 adults with obstructive nephropathy and 30 healthy controls. Kidney function was assessed using the measured glomerular filtration rate (mGFR) through renal clearance of 99mTc-diethylenetriamine penta-acetic acid, along with cystatin C levels. Additionally, glycemic and lipid statuses were evaluated. sUmod concentrations showed a significant association with High-density lipoprotein (HDL) levels. Furthermore, CKD patients with lower sUmod levels had significantly lower Apolipoprotein A-I (Apo A-I) values compared to the control group. Significant predictors of lower sUmod concentrations identified in this study were higher glycemia (B = −15.939; p = 0.003) and lower HDL cholesterol levels (B = 20.588; p = 0.019). We conclude that, in addition to being significantly reduced in CKD patients, sUmod is a potential predictor of metabolic syndrome (MS) in this population. Lower sUmod concentrations, independent of mGFR, predict lower HDL cholesterol levels and higher glycemia values.
Environmental Heat Stress Decreases Sperm Motility by Disrupting the Diurnal Rhythms of Rumen Microbes and Metabolites in Hu Rams
Authors: Wang Qiang-Jun , Yi Huan-Ming , Ou Jing-Yu , Wang Ru , Wang Ming-Ming , Wang Peng-Hui , He Xiao-Long , Tang Wen-Hui , Chen Jia-Hong , Yu Yang , Zhang Chun-Ping , Ren Chun-Huan , Zhang Zi-Jun
Published: October 2024

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae_UCG_001. Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale.
Hepatitis E Virus Infection in Patients with Systemic and Cutaneous Lupus Erythematosus
Authors: Ceccarelli Fulvia , Dorrucci Maria , Pirone Carmelo , Mataj Elida , Garufi Cristina , Farchi Francesca , Bruni Roberto , Villano Umbertina , Madonna Elisabetta , Iaiani Giancarlo , Ciccozzi Massimo , Ciccaglione Anna Rita , Conti Fabrizio , Lo Presti Alessandra
Published: October 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology in which genetic and environmental factors interplay. An exclusively cutaneous condition has been described and defined as cutaneous lupus erythematosus (CLE). In Italy, a nationwide blood donor survey found an overall HEV prevalence of 8.7%, with an interregional variation from 2.2% to 22.8%. In this study, we aimed to estimate HEV seroprevalence in a cohort of patients affected by SLE and CLE attending the Lupus Clinic, Sapienza University of Rome. Serum samples were tested for anti-HEV immunoglobulin Ig G and M antibodies using commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis was performed. In total, 138 patients were enrolled, 92 (67%) affected by SLE and 46 by CLE. The prevalence of HEV infection was 23.9% in the CLE group and 7.6% in the SLE group. The anti-HEV+ prevalence was significantly more frequent in CLE. Some mechanisms may be linked to increased susceptibility to HEV such as a molecular mimicry associated with the CLE condition or with the skin compartment/skin self-antigens, as well as the involvement of the genetic background. Regarding the possible risk factors, no association was found, although, of note, the odds of HEV+ relative to contact with animals and to eating raw seafood were strongly higher than the unit in the CLE group.
Effect of Unfractionated Heparin Dose on Complement Activation and Selected Extracellular Vesicle Populations during Extracorporeal Membrane Oxygenation
Authors: Zipperle Johannes , Vock Laurenz , Fritsch Gerhard , Grillari Johannes , Osuchowski Marcin F. , Holnthoner Wolfgang , Schöchl Herbert , Halbgebauer Rebecca , Huber-Lang Markus , Hofmann Nikolaus , Scharner Vincenz , Panigada Mauro , Gratz Johannes , Iapichino Giacomo
Published: October 2024

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation. We investigated the impact of UFH dose during ECMO therapy at the coagulation–inflammation interface level, focusing on complement activation and changes in circulating large EV (lEV) subsets. In a post hoc analysis of a multicenter randomized controlled trial comparing two anticoagulation management algorithms, we examined lEV levels and complement activation in 23 veno-venous-ECMO patients stratified by UFH dose. Blood samples were collected at different time points and grouped into three phases of ECMO therapy: initiation (day 1), mid (days 3–4), and late (days 6–7). Immunoassays detected complement activation, and flow cytometry analyzed lEV populations with an emphasis on mitochondria-carrying subsets. Patients receiving <15 IU/kg/h UFH exhibited higher levels of the complement activation product C5a and soluble terminal complement complex (sC5b-9). Lower UFH doses were linked to increased endothelial-derived lEVs, while higher doses were associated with elevated RBC-derived and mitochondria-positive lEVs. Our findings suggest the potential theranostic relevance of EV detection at the coagulation–inflammation interface. Further research is needed to standardize EV detection methods and validate these findings in larger ECMO patient cohorts.
The Evolution of NLR Inflammasome and Its Mediated Pyroptosis in Metazoa
Authors: Sun Jiejie , Leng Jinyuan , Song Linsheng
Published: October 2024

Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) inflammasomes are multiprotein signaling platforms that control the inflammatory response and coordinate antimicrobial defense. In the present study, the distribution of NLR, Caspase-1, and gasdermin (GSDM) homologues and their structural characteristics and evolutionary relationships were systematically analyzed in metazoa according to the genomes of species. In invertebrates, there were only NLRC and/or NLRD presented from sponge to amphioxus, and according to the evolutionary tree, NLR from sponge located in the most primitive position. Caspase-1 existed in some metazoan phyla (Brachiopoda, Ectoprocta, Arthropoda, Mollusca, Annelia, Nematoda, Platyelminthes, Coelenterate, and Porifera) and its activation sites were relatively conserved. The amino acid sequences and three-dimensional structures of N-terminal CARD/Death domain of NLR and Caspase-1 were similar in species from sponge to human. NLR and Caspase-1 co-existed in species of Brachiopoda, Mollusca, Annelia, Coelenterate, and Porifera. There was only GSDME or PJVK found in some phyla of invertebrates and their cleavage sites were conserved (DxxD). And it was predicted that the NLR inflammasome in inducing pyroptosis could occur in species of Brachiopoda, Mollusca, Annelia, and Coelenterate. These studies indicated that NLR inflammasome emerged early in sponges of metazoa, and NLR inflammasome in inducing pyroptosis first appeared in Coelenterate, suggesting that inflammasome and its mediated pyroptosis had existed in the early stage of metazoa, but they had been lost in many species during evolution.
Early Diagnosis and Treatment of Kidney Injury: A Focus on Urine Protein
Authors: Zeng Duanna , Wang Bing , Xiao Zheng , Wang Xiongqin , Tang Xiyang , Yao Xinsheng , Wang Ping , Li Meifang , Dai Yi , Yu Xiean
Published: October 2024

The kidney, an essential excretory organ of the body, performs a series of crucial physiological functions such as waste removal, maintenance of electrolyte and acid–base balance, and endocrine regulation. Due to its rich blood flow and high metabolic activity, the kidney is susceptible to damage. Currently, kidney injury is classified into acute kidney injury (AKI) and chronic kidney disease (CKD), both of which are associated with high rates of morbidity and mortality on a global scale. The current clinical diagnosis of renal injury relies on the assessment of renal filtration function using creatinine and urea nitrogen as “gold-standard” markers. However, the delayed response time, limited specificity, and reduced accuracy of creatinine and urea nitrogen in evaluating kidney injury have significantly hindered advancements in diagnostic methods for kidney injury. Urinary protein is widely utilized as a biomarker for the early diagnosis of kidney injury due to the selectivity of the glomerular filtration system determining whether proteins can pass through the filtration barrier based on their size and charge. Therefore, as a complex biological sample with varying charges and particle sizes, urinary protein is considered an ideal indicator for monitoring the progression of kidney disease. Exploring the relationship between urinary protein and the advancement of kidney injury based on differences in particle size and charge offers a new perspective for assessing and treating such injuries. Hence, we conducted a comprehensive review of 74 relevant studies to gain a thorough understanding of the physiological mechanism and significance of proteinuria production. The aim was to explore the challenges and opportunities in clinical urine protein detection, as well as to discuss strategies targeting glomerular filtration barriers in order to effectively reduce urine protein levels and treat kidney injury, which could provide a new perspective for identifying the progression of kidney injury.
Genome-Scale Identification of Wild Soybean Serine/Arginine-Rich Protein Family Genes and Their Responses to Abiotic Stresses
Authors: Wang Yanping , Wang Xiaomei , Zhang Rui , Chen Tong , Xiao Jialei , Li Qiang , Ding Xiaodong , Sun Xiaohuan
Published: October 2024

Serine/arginine-rich (SR) proteins mostly function as splicing factors for pre-mRNA splicing in spliceosomes and play critical roles in plant development and adaptation to environments. However, detailed study about SR proteins in legume plants is still lacking. In this report, we performed a genome-wide investigation of SR protein genes in wild soybean (Glycine soja) and identified a total of 31 GsSR genes from the wild soybean genome. The analyses of chromosome location and synteny show that the GsSRs are unevenly distributed on 15 chromosomes and are mainly under the purifying selection. The GsSR proteins can be phylogenetically classified into six sub-families and are conserved in evolution. Prediction of protein phosphorylation sites indicates that GsSR proteins are highly phosphorylated proteins. The protein–protein interaction network implies that there exist numerous interactions between GsSR proteins. We experimentally confirmed their physical interactions with the representative SR proteins of spliceosome-associated components such as U1-70K or U2AF35 by yeast two-hybrid assays. In addition, we identified various stress-/hormone-responsive cis-acting elements in the promoter regions of these GsSR genes and verified their expression patterns by RT-qPCR analyses. The results show most GsSR genes are highly expressed in root and stem tissues and are responsive to salt and alkali stresses. Splicing analysis showed that the splicing patterns of GsSRs were in a tissue- and stress-dependent manner. Overall, these results will help us to further investigate the biological functions of leguminous plant SR proteins and shed new light on uncovering the regulatory mechanisms of plant SR proteins in growth, development, and stress responses.
p57Kip2 Phosphorylation Modulates Its Localization, Stability, and Interactions
Authors: Stampone Emanuela , Bencivenga Debora , Dassi Luisa , Sarnelli Sara , Campagnolo Luisa , Lacconi Valentina , Della Ragione Fulvio , Borriello Adriana
Published: October 2024

p57Kip2 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21Cip1/WAF1 and p27Kip1. Different from its siblings, few data are available about the p57Kip2 protein, especially in humans. Structurally, p57Kip2 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein. Being an IUP, its localization, stability, and binding to functional partners might be strongly modulated by post-translational modifications, especially phosphorylation. In this work, we investigated by two-dimensional analysis the phosphorylation pattern of p57Kip2 in different cellular models, revealing how the human protein appears to be extensively phosphorylated, compared to p21Cip1/WAF1 and p27Kip1. We further observed clear differences in the phosphoisoforms distributed in the cytosolic and nuclear compartments in asynchronous and synchronized cells. Particularly, the unmodified form is detectable only in the nucleus, while the more acidic forms are present in the cytoplasm. Most importantly, we found that the phosphorylation state of p57Kip2 influences the binding with some p57Kip2 partners, such as CDKs, LIMK1 and CRM1. Thus, it is necessary to completely identify the phosphorylated residues of the protein to fully unravel the roles of this CIP/Kip protein, which are still partially identified.
Comparative Phylogenomic Study of Malaxidinae (Orchidaceae) Sheds Light on Plastome Evolution and Gene Divergence
Authors: Zeng Meng-Yao , Li Ming-He , Lan Siren , Yin Wei-Lun , Liu Zhong-Jian
Published: October 2024

Malaxidinae is one of the most confusing groups in the Orchidaceae classification. Previous phylogenetic analyses have revealed that the relationships between the taxa in Malaxidinae have not yet been reliably established, using only a few plastome regions and nuclear ribosomal internal transcribed spacer (nrITS). In the present study, the complete plastomes of Oberonia integerrima and Crepidium purpureum were assembled using high-throughput sequencing. Combined with publicly available complete plastome data, this resulted in a dataset of 19 plastomes, including 17 species of Malaxidinae. The plastome features and phylogenetic relationships were compared and analyzed. The results showed the following: (1) Malaxidinae species plastomes possess the quadripartite structure of typical angiosperms, with sizes ranging from 142,996 to 158,787 bp and encoding from 125 to 133 genes. The ndh genes were lost or pseudogenized to varying degrees in six species. An unusual inversion was detected in the large single-copy region (LSC) of Oberonioides microtatantha. (2) Eight regions, including ycf1, matK, rps16, rpl32, ccsA-ndhD, clpP-psbB, trnFGAA-ndhJ, and trnSGCU-trnGUCC, were identified as mutational hotspots. (3) Based on complete plastomes, 68 protein-coding genes, and 51 intergenic regions, respectively, our phylogenetic analyses revealed the genus-level relationships in this subtribe with strong support. The Liparis was supported as non-monophyletic.
Application of hs-CRP in Assessment of Tissue Inflammation Following Implantation of Biodegradable Polymer in Experiment
Authors: Eisenach Igor A. , Lapii Galina A. , Uzyumova Alexandra K. , Lushnikova Elena L. , Ovchinnikov Victor S. , Solovieva Anastasia O. , Naprimerov Vasiliy A.
Published: October 2024

Implants made of biodegradable polymers are replaced by regenerating tissues through inflammation. The changes occurring in tissues and the organism are of practical interest for studying the biocompatibility of the material and searching for systemic markers in the blood that reflect inflammation in peri-implantation tissues. The highly sensitive C-reactive protein (hs-CRP) measurements in blood and morphometric studies of tissue surrounding the implant were carried out in the experiment within three months of implantation of a biopolymer consisting of polycaprolactone (PCL) and polytrimethylene carbonate (PTMC). During the first month, tissue inflammation decreased, and the blood level of hs-CRP did not increase. The polymer biotransformation began in the tissues after a month of implantation and was accompanied by inflammation moving deeper into the matrix. Proliferation of inflammatory cells in tissues was reflected in an increase in the hs-CRP level three months after polymer installation. The result achieved confirmed the polymer’s bioinertness. The level of hs-CRP in the blood of the animals correlated with the level of inflammation in peri-implantation tissues, reflecting the activity of inflammation in the process of polymer biotransformation. This inflammation protein can be recommended for assessing tissue processes following implantation of biopolymers and their biocompatibility.
Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment
Authors: Singh Manish Kumar , Han Sunhee , Kim Sungsoo , Kang Insug
Published: October 2024

Cancer stem cells (CSCs), or tumor-initiating cells (TICs), are small subpopulations (0.0001–0.1%) of cancer cells that are crucial for cancer relapse and therapy resistance. The elimination of each CSC is essential for achieving long-term remission. Metabolic reprogramming, particularly lipids, has a significant impact on drug efficacy by influencing drug diffusion, altering membrane permeability, modifying mitochondrial function, and adjusting the lipid composition within CSCs. These changes contribute to the development of chemoresistance in various cancers. The intricate relationship between lipid metabolism and drug resistance in CSCs is an emerging area of research, as different lipid species play essential roles in multiple stages of autophagy. However, the link between autophagy and lipid metabolism in the context of CSC regulation remains unclear. Understanding the interplay between autophagy and lipid reprogramming in CSCs could lead to the development of new approaches for enhancing therapies and reducing tumorigenicity in these cells. In this review, we explore the latest findings on lipid metabolism in CSCs, including the role of key regulatory enzymes, inhibitors, and the contribution of autophagy in maintaining lipid homeostasis. These recent findings may provide critical insights for identifying novel pharmacological targets for effective anticancer treatment.
Flavonoids and Their Role in Preventing the Development and Progression of MAFLD by Modifying the Microbiota
Authors: Sokal-Dembowska Aneta , Jarmakiewicz-Czaja Sara , Filip Rafał
Published: October 2024

With the increasing prevalence and serious health consequences of metabolic-associated fatty liver disease (MAFLD), early diagnosis and intervention are key to effective treatment. Recent studies highlight the important role of dietary factors, including the use of flavonoids, in improving liver health. These compounds possess anti-inflammatory, antioxidant, and liver-protective properties. Flavonoids have been shown to affect the gut microbiota, which plays a key role in liver function and disease progression. Therefore, their role in preventing the development and progression of MAFLD through modulation of the microbiome seems to be of interest. This narrative review aims to consolidate the current evidence on the effects of selected flavonoids on MAFLD progression, their potential mechanisms of action, and the implications for the development of personalized dietary interventions for the management of liver disease.
Inflammation, Gut Microbiota, and Metabolomic Shifts in Colorectal Cancer: Insights from Human and Mouse Models
Authors: Yang Chengcong , Wusigale  , You Lijun , Li Xiang , Kwok Lai-Yu , Chen Yongfu
Published: October 2024

Colorectal cancer (CRC) arises from aberrant mutations in colorectal cells, frequently linked to chronic inflammation. This study integrated human gut metagenome analysis with an azoxymethane and dextran sulfate sodium-induced CRC mouse model to investigate the dynamics of inflammation, gut microbiota, and metabolomic profiles throughout tumorigenesis. The analysis of stool metagenome data from 30 healthy individuals and 40 CRC patients disclosed a significant escalation in both gut microbiota diversity and abundance in CRC patients compared to healthy individuals (p < 0.05). Marked structural disparities were identified between the gut microbiota of healthy individuals and those with CRC (p < 0.05), characterized by elevated levels of clostridia and diminished bifidobacteria in CRC patients (p < 0.05). In the mouse model, CRC mice exhibited distinct gut microbiota structures and metabolite signatures at early and advanced tumor stages, with subtle variations noted during the intermediate phase. Additionally, inflammatory marker levels increased progressively during tumor development in CRC mice, in contrast to their stable levels in healthy counterparts. These findings suggest that persistent inflammation might precipitate gut dysbiosis and altered microbial metabolism. Collectively, this study provides insights into the interplay between inflammation, gut microbiota, and metabolite changes during CRC progression, offering potential biomarkers for diagnosis. While further validation with larger cohorts is warranted, the data obtained support the development of CRC prevention and diagnosis strategies.
The Co-Design of a Locally Led Health Professional Education Curriculum in Lao People’s Democratic Republic
Authors: Gray Amy , Phommachanh Sysavanh , Phoumindr Niranh , Mayxay Mayfong
Published: October 2024

(1) Background: There is a need to scale and transform health professional education (HPE) globally to not only improve the quantity but also the quality of health workers. This paper describes the approach undertaken by a Health University in Lao PDR. (2) Approach: The HPE curriculum was designed in an iterative process with key stakeholders from both the institution and government, with external expert advice. (3) Outcomes: The curriculum was successfully developed consisting of nine core modules and one elective module, reflecting both elements seen globally in HPE curricula as well as reflecting local needs. The content and teaching methods were validated and reviewed through piloting with local education leaders. (4) Conclusions: Despite the need to scale HPE globally, there are few examples of how this can be achieved in countries in which large gaps exist in HPE capacity. This paper provides one such example, through recognizing that sustained external partnerships will still be needed for successful future implementation.
Seroprevalence of Antibodies to Brucella spp. and Neospora caninum in Cattle from Delta Region of Egypt: Correlation of Seropositivity with Abortion History
Authors: Fereig Ragab M. , Mazeed Amira M. , Alharbi Azzah S. , Abdelraheem Mona Z. , Omar Mosaab A. , Almuzaini Abdulaziz M. , El-Diasty Mohamed , Elsharkawy Hend I. , Sobhy Kamel , Frey Caroline F. , Wareth Gamal
Published: October 2024

Bovine brucellosis and neosporosis are reported as potential abortifacient infections in cattle worldwide. Brucellosis is additionally a zoonotic bacterial infection caused by numerous Brucella species. Meanwhile, neosporosis is a protozoan parasitic disease that is implicated in causing high economic losses in the cattle industry. Herein, we attempted to investigate the seroprevalence of specific antibodies to Brucella spp. and Neospora caninum using commercially available ELISAs. In addition, we conducted risk factor analysis and estimated the correlation of seropositivity of both pathogens with the recorded abortions in the tested herds. Serum samples from cattle (n = 460) collected from various governorates in the Delta region, northern Egypt, were targeted in this study. Overall, a seroprevalence of 5.4%, 33.3%, and 1.3% was revealed for Brucella spp., N. caninum, and mixed seropositivity, respectively. The location (Kafr El Sheikh vs. Dakahlia vs. Al-Qalyubiya vs. Damietta governorates) and a history of abortion (yes vs. no vs. unknown) were analyzed as risk factors of infection. Kafr El Sheikh governorate (57.7%, p = < 0.0001) and a history of abortion (54.1%, p = < 0.0001) were considered risk factors for Brucella spp. seropositivity compared to the reference factors Al-Qalyubiya (1.1%) and unknown abortion history (0.6%). In the case of N. caninum, the location was also considered a risk factor because the seropositive rates were significantly higher in Damietta (51%, p = 0.001) and Dakahlia (33.4%, p = 0.026) compared to Kafr El Sheikh (11.3%, set as a reference). Conversely to Brucella, animals without a history of abortion exhibited a higher seropositive rate for N. caninum (47.6%, p = 0.009) compared to those with a history of abortion (21.6%, set as reference). For further investigations into the association between abortion and the obtained seropositive rates, we also analyzed the reactivity by comparing samples of animals with, without, and unknown history of abortion. We detected high seroreactivity for Brucella spp. in samples collected from animals with a history of abortion, as demonstrated in the recorded antibody levels and correlation coefficient (Pearson r = 0.919). Based on our data, despite the higher seroprevalence of N. caninum compared to that of Brucella species, Brucella spp. might be the primary cause of abortion in our tested cattle population.
Image Stitching of Low-Resolution Retinography Using Fundus Blur Filter and Homography Convolutional Neural Network
Authors: Santos Levi , Almeida Maurício , Almeida João , Braz Geraldo , Camara José , Cunha António
Published: October 2024

Great advances in stitching high-quality retinal images have been made in recent years. On the other hand, very few studies have been carried out on low-resolution retinal imaging. This work investigates the challenges of low-resolution retinal images obtained by the D-EYE smartphone-based fundus camera. The proposed method uses homography estimation to register and stitch low-quality retinal images into a cohesive mosaic. First, a Siamese neural network extracts features from a pair of images, after which the correlation of their feature maps is computed. This correlation map is fed through four independent CNNs to estimate the homography parameters, each specializing in different corner coordinates. Our model was trained on a synthetic dataset generated from the Microsoft Common Objects in Context (MSCOCO) dataset; this work added an important data augmentation phase to improve the quality of the model. Then, the same is evaluated on the FIRE retina and D-EYE datasets for performance measurement using the Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM). The obtained results are promising: the average PSNR was 26.14 dB, with an SSIM of 0.96 on the D-EYE dataset. Compared to the method that uses a single neural network for homography calculations, our approach improves the PSNR by 7.96 dB and achieves a 7.86% higher SSIM score.
Flexural Behavior of Concrete-Filled Steel Tube Beams Composite with Concrete Slab Deck
Authors: AlObaidi Salam Maytham , Mousa Mohammed Abbas , Almusawi Aqil M. , Shallal Muhaned A. , Alzabeebee Saif
Published: October 2024

Concrete-filled steel tube (CFST) beams have shown their flexural effectiveness in terms of stiffness, strength, and ductility. On the other hand, composite bridge girders demand durable and ductile girders to serve as tension members, while the concrete deck slab resists the compression stresses. In this study, six composite CFST beams with concrete slab decks with a span of 170 cm were investigated under a four-point bending test. The main variables of the study were the compressive strength of the concrete deck, the size of CFST beams, and the composite mechanism between the CFST girder and the concrete deck. The results showed that the flexural strength and ductility of the composite system increased by 20% with increasing concrete compressive strength. The study revealed that the higher-strength concrete slab deck enabled the CFST beam to exhibit improved flexural behavior with reduced deflections and enhanced resistance to cracking. The findings also highlighted the importance of considering the interactions between the steel tube and concrete slab deck in determining the flexural behavior of the composite system revealed by strain distribution along the composite beam profile as determined using the digital image correlation DIC technique, where a 40% increase in the flexural strength was obtained when a channel section was added to the joint of the composite section.
Impact of Comorbidities and Skin Diseases on Post-Vaccination Reactions: A Study on COVID-19 Vaccinations in Poland
Authors: Jęśkowiak-Kossakowska Izabela , Nowotarska Paulina , Grosman-Dziewiszek Patrycja , Szeląg Adam , Wiatrak Benita
Published: October 2024

Background: The COVID-19 pandemic necessitated rapid and widespread vaccination efforts, which proved critical in reducing the severity and mortality of the virus. However, the interplay between vaccinations, pre-existing skin conditions, and other comorbidities still needs to be explored. This study investigated the occurrence and severity of adverse events following immunization (AEFIs) with COVID-19 vaccines in individuals with chronic skin diseases and comorbidities within a Central European cohort. Methods: An anonymous online survey was conducted between May 2022 and February 2023, targeting students and employees of universities in Wrocław, Poland. A total of 513 respondents were analyzed, focusing on AEFIs following the first, second, and third doses of COVID-19 vaccines and the effects of COVID-19 on conditions such as atopic dermatitis, psoriasis, vitiligo, acne vulgaris, rosacea, and various comorbidities. Results: COVID-19 vaccination effectively protected against severe disease across all doses. The analysis revealed no significant impact of either COVID-19 infection or vaccination on the course of selected skin diseases and comorbidities. The reporting of AEFIs to the Sanitary Inspection was notably low. The Moderna and Pfizer mRNA-based vaccines were associated with a higher reported number of AEFIs, particularly after the second and third doses, compared to AstraZeneca, which exhibited fewer adverse events after subsequent doses. Conclusions: COVID-19 vaccination is both safe and effective, even in patients with pre-existing skin conditions and comorbidities. Vaccine selection may benefit from considering individual health profiles, and better reporting of AEFIs is needed to enhance vaccine safety monitoring.
Treatment Strategies’ Impact on Progression-Free Survival According to RMST Function in Metastatic Colorectal Cancer Patients: A Retrospective Study from Romania
Authors: Pirvu Edvina Elena , Severin Emilia , Patru Raluca Ileana , Nita Irina , Toma Stefania Andreea , Croitoru Bianca Elena , Munoz Groza Adriana Estefa , Marinescu Gabriela
Published: October 2024

Background: This retrospective study investigates the impact of various treatment strategies on progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), a significant global health issue. Methods: We employed the restricted mean survival time (RMST) to evaluate how different treatments affect PFS over a defined period. The study included 225 patients with mCRC who were treated between 2015 and 2023 at the Oncology Department of Colțea Clinical Hospital in Bucharest. To assign KRAS status, mutation data from exons 2, 3, and 4 of the KRAS gene were required. Eligibility criteria included a confirmed histopathological diagnosis of colorectal adenocarcinoma, a valid RAS mutation test from a solid biopsy, radiological confirmation of stage IV disease by computed tomography, and at least one line of systemic treatment in the metastatic setting. Results: Our analysis revealed a small difference in PFS based on KRAS status, but this difference was not statistically significant. Neither sex nor the urban versus rural environment impacted PFS; however, the data indicated that educational level affected survival outcomes. Conclusions: Consistent with existing literature, our findings showed no survival benefit from locoregional treatments such as surgery of the primary tumor or curative radiotherapy at diagnosis. In contrast, resection of hepatic metastases was associated with improved survival outcomes.