bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcus aureus Stress Response to Bicarbonate Depletion
Authors: Liberini Elisa , Fan Sook-Ha , Bayer Arnold S. , Beck Christian , Biboy Jacob , François Patrice , Gray Joe , Hipp Katharina , Koch Iris , Peschel Andreas , Sailer Brigitte , Vollmer Daniela , Vollmer Waldemar , Götz Friedrich
Published: August 2024

Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. An mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2/bicarbonate deficiency. Electron microscopy revealed that ΔmpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant’s lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower α-glycosylated and higher ß-glycosylated WTA, explaining the mutant’s increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, like in vancomycin-intermediate S. aureus mutants (VISA). Genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents.
The Combination of Natural Compounds Escin–Bromelain–Ginkgo Biloba–Sage Miltiorrhiza (EBGS) Reduces Platelet Adhesion to TNFα-Activated Vascular Endothelium through FAK Signaling
Authors: Barreca Maria Magdalena , Raimondo Stefania , Conigliaro Alice , Siragusa Sergio , Napolitano Mariasanta , Alessandro Riccardo , Corrado Chiara
Published: August 2024

Thrombosis is a key process that determines acute coronary syndrome and ischemic stroke and is the leading cause of morbidity and mortality in the world, together with cancer. Platelet adhesion and subsequent activation and aggregation are critical processes that cause thrombus formation after endothelial damage. To date, high hopes are associated with compounds of natural origin, which show anticoagulant action without undesirable effects and can be proposed as supportive therapies. We investigated the effect of the new combination of four natural compounds, escin–bromelain–ginkgo biloba–sage miltiorrhiza (EBGS), on the initial process of the coagulation cascade, which is the adhesion of platelets to activated vascular endothelium. Our results demonstrated that EBGS pretreatment of endothelial cells reduces platelet adhesion even in the presence of the monocyte–lymphocyte population. Our data indicate that EBGS exerts its effects by inhibiting the transcription of adhesion molecules, including P-selectin, platelet membrane glycoprotein GP1b, integrins αV and β3, and reducing the secretion of the pro-inflammatory cytokines interleukin 6, interleukin 8, and the metalloproteinases MMP-2 and MMP-9. Furthermore, we demonstrated that EBGS inhibited the expression of focal adhesion kinase (FAK), strictly involved in platelet adhesion, and whose activity is correlated with that of integrin β3. The results shown in this manuscript suggest a possible inhibitory role of the new combination EBGS in the reduction in platelet adhesion to activated endothelium, thus possibly preventing coagulation cascade initiation.
Nanotechnology Advances in the Detection and Treatment of Lymphoid Malignancies
Authors: Adamo Francesco Maria , De Falco Filomena , Dorillo Erica , Sorcini Daniele , Stella Arianna , Esposito Angela , Arcaleni Roberta , Rosati Emanuela , Sportoletti Paolo
Published: August 2024

Lymphoid malignancies are complex diseases with distinct biological behaviors, clinical presentations, and treatment responses. Ongoing research and advancements in biotechnology enhance the understanding and management of these malignancies, moving towards more personalized approaches for diagnosis and treatment. Nanotechnology has emerged as a promising tool to improve some limitations of conventional diagnostics as well as treatment strategies for lymphoid malignancies. Nanoparticles (NPs) offer unique advantages such as enhanced multimodal detection, drug delivery, and targeted therapy capabilities, with the potential to improve precision medicine and patient outcomes. Here, we comprehensively examine the current landscape of nanoconstructs applied in the management of lymphoid disease. Through a comprehensive analysis of preclinical studies, we highlight the translational potential of NPs in revolutionizing the field of hematological malignancies, with a specific focus on lymphoid neoplasms.
Evaluation of Clobetasol and Tacrolimus Treatments in an Imiquimod-Induced Psoriasis Rat Model
Authors: Guillaume Philippe , Rupp Tristan , Froget Guillaume , Goineau Sonia
Published: August 2024

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, inflammation, and aberrant differentiation. Imiquimod-induced psoriasis in rodent models has been widely used to study the pathogenesis of the disease and evaluate potential therapeutic interventions. In this study, we investigated the efficacy of two commonly used treatments, Clobetasol and Tacrolimus, in ameliorating psoriatic symptoms in an Imiquimod-induced psoriasis Wistar rat model. Interestingly, rat models are poorly evaluated in the literature despite rats displaying several advantages in evaluating pharmacological substances. Psoriasis-like skin lesions were induced by topical application of Imiquimod cream on shaved dorsal skin for seven consecutive days. Following induction, rats in the treatment groups received either a Clobetasol or Tacrolimus ointment once daily for one week, while the control group did not receive any application. Disease severity was assessed using clinical scoring, histological examination, and measurement of proinflammatory cytokine levels. Both Clobetasol and Tacrolimus treatments significantly reduced psoriatic lesion severity compared to the control group. Clinical scoring revealed a decrease in erythema, scaling, transepidermal water loss, and thickness of skin lesions in both treatment groups with a more marked effect with Clobetasol. Histological analysis demonstrated reduced epidermal hyperplasia in treated animals compared to controls. Furthermore, Clobetasol led to a significant reduction in the expression levels of the interleukin-17 (IL-17a and IL-17f) proinflammatory cytokines in lesioned skin. Overall, our findings demonstrated the therapeutic efficacy of both Clobetasol and, in a modest manner, Tacrolimus in attenuating Imiquimod-induced psoriasis-like symptoms in a rat model. These results support the clinical use of these agents in the management of psoriasis and mitigating psoriatic inflammation. They also provide insights into the use of rats as a relevant species for the Imiquimod-induced psoriasis model.
The Role of Natural Products in Immunopharmacology
Authors: Accardi Giulia , Di Majo Danila , Aiello Anna
Published: August 2024

The Special Issue “The Role of Natural Products in Immunopharmacology”, edited by Giulia Accardi, Danila Di Majo, and Anna Aiello focuses on the crucial role of natural products and their related components in treating various disorders, emphasizing their applications in the pharmacological and nutraceutical fields [...]
Endothelial Cell-Derived Soluble CD200 Determines the Ability of Immune Cells to Cross the Blood–Brain Barrier
Authors: Pujol Myriam , Paskevicius Tautvydas , Robinson Alison , Dhillon Simran , Eggleton Paul , Ferecskó Alex S. , Gutowski Nick , Holley Janet , Smallwood Miranda , Newcombe Jia , Agellon Luis B. , Michalak Marek
Published: August 2024

The infiltration of immune cells into the central nervous system mediates the development of autoimmune neuroinflammatory diseases. We previously showed that the loss of either Fabp5 or calnexin causes resistance to the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Here we show that brain endothelial cells lacking either Fabp5 or calnexin have an increased abundance of cell surface CD200 and soluble CD200 (sCD200) as well as decreased T-cell adhesion. In a tissue culture model of the blood–brain barrier, antagonizing the interaction of CD200 and sCD200 with T-cell CD200 receptor (CD200R1) via anti-CD200 blocking antibodies or the RNAi-mediated inhibition of CD200 production by endothelial cells increased T-cell adhesion and transmigration across monolayers of endothelial cells. Our findings demonstrate that sCD200 produced by brain endothelial cells regulates immune cell trafficking through the blood–brain barrier and is primarily responsible for preventing activated T-cells from entering the brain.
New Horizons in the Diagnosis of Gastric Cancer: The Importance of Selected Toll-like Receptors in Immunopathogenesis Depending on the Stage, Clinical Subtype, and Gender of Newly Diagnosed Patients
Authors: Kos Marek , Bojarski Krzysztof , Mertowska Paulina , Mertowski Sebastian , Tomaka Piotr , Dziki Łukasz , Grywalska Ewelina
Published: August 2024

Introduction: Toll-like receptors (TLRs) play a vital role in the innate immune response, recognizing pathogens and initiating the inflammatory response. Research suggests that TLRs may also have a significant impact on the development and progression of cancers, including gastric cancer (GC). Understanding the role of individual TLRs in the immunopathogenesis of gastric cancer may provide new information necessary to develop more effective diagnostic and therapeutic methods. Aim of the study: This study aimed to determine the role of selected TLR-2, -3, -4, and -9 in the immunopathogenesis of patients with newly diagnosed and untreated gastric cancer. Materials and methods: The study included 60 newly diagnosed, untreated GC patients and 25 healthy volunteers. The research included analyses assessing the percentage of the tested TLRs on T and B lymphocyte subpopulations using multicolor flow cytometry and assessing their concentration in the serum of the examined patients using ELISA tests. The statistical analyses performed included a comparison of patients in individual stages of gastric cancer, an analysis of the most common clinical subtypes of gastric cancer, and a comparative analysis of differences in the gender of recruited patients. Results: Our studies showed different expression levels of TLR-2, -3, -4, and -9 on T and B lymphocyte subpopulations, as well as their different concentrations in patients’ serum. Significant differences in the expression of these receptors were observed depending on the stage of gastric cancer and its clinical subtypes. These differences were also visible in the context of patient gender. Summary: The results of our studies suggest that TLR-2, -3, -4, and -9 may play an important role in the immunopathogenesis of gastric cancer. The differential expression of these receptors depending on the stage of the disease, clinical subtype, and gender of patients may have potential diagnostic and therapeutic significance. Further research is necessary to understand better the mechanisms of action of TLRs in gastric cancer and to apply this knowledge in clinical practice.
Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors
Authors: Park Gun-Hoo , Park Eunkuk , Lee Su-Jin , Lim Kyubin , Kim Jeonghyun , Park Jun Eun , Jeong Seon-Yong
Published: August 2024

Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.
Neonatal Fungemia by Non-Candida Rare Opportunistic Yeasts: A Systematic Review of Literature
Authors: Mpakosi Alexandra , Cholevas Vasileios , Meletiadis Joseph , Theodoraki Martha , Sokou Rozeta
Published: August 2024

Fungal colonization poses a significant risk for neonates, leading to invasive infections such as fungemia. While Candida species are the most commonly identified pathogens, other rare yeasts are increasingly reported, complicating diagnosis and treatment due to limited data on antifungal pharmacokinetics. These emerging yeasts, often opportunistic, underscore the critical need for early diagnosis and targeted therapy in neonates. This systematic review aims to comprehensively analyze all published cases of neonatal fungemia caused by rare opportunistic yeasts, examining geographical distribution, species involved, risk factors, treatment approaches, and outcomes. Searching two databases (PubMed and SCOPUS), 89 relevant studies with a total of 342 cases were identified in the 42-year period; 62% of the cases occurred in Asia. Pichia anomala (31%), Kodamaea ohmeri (16%) and Malassezia furfur (15%) dominated. Low birth weight, the use of central catheters, prematurity, and the use of antibiotics were the main risk factors (98%, 76%, 66%, and 65%, respectively). 22% of the cases had a fatal outcome (80% in Asia). The highest mortality rates were reported in Trichosporon beigelii and Trichosporon asahii cases, followed by Dirkmeia churashimamensis cases (80%, 71%, and 42% respectively). Low birth weight, the use of central catheters, the use of antibiotics, and prematurity were the main risk factors in fatal cases (84%, 74%, 70%, and 67%, respectively). 38% of the neonates received fluconazole for treatment but 46% of them, died. Moreover, the rare yeasts of this review showed high MICs to fluconazole and this should be taken into account when planning prophylactic or therapeutic strategies with this drug. In conclusion, neonatal fungemia by rare yeasts is a life-threatening and difficult-to-treat infection, often underestimated and misdiagnosed.
Galectin-1 Attenuates PDGF-Mediated AKT Signaling in Retinal Pigment Epithelial Cells
Authors: Bizzotto Martina , Ostermaier Annabella , Liesenhoff Caspar , Ma Wenxiu , Geerlof Arie , Priglinger Siegfried G. , Priglinger Claudia S. , Ohlmann Andreas
Published: August 2024

Galectins have the potential to interact with transmembrane glycoproteins to modulate their functions. Since galectin-1 interacts with PDGF-Rβ, we analyzed the effect of galectin-1 on PDGF-BB-mediated AKT signaling in primary human retinal pigment epithelial (RPE) cells and galectin-1-deficient immortalized human RPE cells (LGALS1−/−/ARPE-19) following incubation with PDGF-BB and galectin-1. Expression and localization of galectin-1, PDGF-Rβ and pAKT were investigated using western blot analysis and immunohistochemical staining. Cell proliferation of RPE cells was analyzed using BrdU ELISA. Following treatment of human RPE cells with human recombinant (hr)-galectin-1 and PDGF-BB, an intense clustering of PDGF-Rβ and colocalization with galectin-1 were detected. By Western blot analysis and immunocytochemistry of human RPE cells, an enhanced PDGF-BB-mediated expression of pAKT was observed, which was substantially reduced by additional incubation with hr-galectin-1. Vice versa, in LGALS1−/−/ARPE-19 cells, the PDGF-BB-induced pAKT signal was enhanced compared to wild-type cells. Furthermore, a decreased expression of PDGF-Rβ in human RPE cells was observed after treatment with PDGF-BB and hr-galectin-1, while in untreated LGALS1−/−/ARPE-19 cells, its constitutive expression was increased. In addition, after treatment of RPE cells with hr-galectin-1, the PDGF-BB-induced proliferation was markedly reduced. In summary, galectin-1 has the distinct potential to reduce PDGF-mediated pAKT signaling and proliferation in human RPE cells—an effect that is most likely facilitated via a decreased expression of PDGF-Rβ.
Isopropyl 3-(3,4-Dihydroxyphenyl)-2-hydroxypropanoate Alleviates Palmitic Acid-Induced Vascular Aging in HUVEC Cells through ROS/Ferroptosis Pathway
Authors: He Xin , Zheng Xiaohui , Xie Weidong
Published: August 2024

Vascular aging is an important factor leading to cardiovascular diseases such as hypertension and atherosclerosis. Hyperlipidemia or fat accumulation may play an important role in vascular aging and cardiovascular disease. Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) has biological activity and can exert cardiovascular protection, which may be related to ferroptosis. However, the exact mechanism remains undefined. We hypothesized that IDHP may have a protective effect on blood vessels by regulating vascular aging caused by hyperlipidemia or vascular wall fat accumulation. The aim of this study is to investigate the protective effect and mechanism of IDHP on palmitic acid-induced human umbilical vein endothelial cells (HUVEC) based on senescence and ferroptosis. We found that IDHP could delay vascular aging, reduce the degree of ferrous ion accumulation and lipid peroxidation, and protect vascular cells from injury. These effects may be achieved by attenuating excessive reactive oxygen species (ROS) and ferroptosis signaling pathways generated in vascular endothelial cells. In short, our study identified IDHP as one of the antioxidant agents to slow down lipotoxicity-induced vascular senescence through the ROS/ferroptosis pathway. IDHP has new medicinal value and provides a new therapeutic idea for delaying vascular aging in patients with dyslipidemia.
A Point Cloud Graph Neural Network for Protein–Ligand Binding Site Prediction
Authors: Zhao Yanpeng , He Song , Xing Yuting , Li Mengfan , Cao Yang , Wang Xuanze , Zhao Dongsheng , Bo Xiaochen
Published: August 2024

Predicting protein–ligand binding sites is an integral part of structural biology and drug design. A comprehensive understanding of these binding sites is essential for advancing drug innovation, elucidating mechanisms of biological function, and exploring the nature of disease. However, accurately identifying protein–ligand binding sites remains a challenging task. To address this, we propose PGpocket, a geometric deep learning-based framework to improve protein–ligand binding site prediction. Initially, the protein surface is converted into a point cloud, and then the geometric and chemical properties of each point are calculated. Subsequently, the point cloud graph is constructed based on the inter-point distances, and the point cloud graph neural network (GNN) is applied to extract and analyze the protein surface information to predict potential binding sites. PGpocket is trained on the scPDB dataset, and its performance is verified on two independent test sets, Coach420 and HOLO4K. The results show that PGpocket achieves a 58% success rate on the Coach420 dataset and a 56% success rate on the HOLO4K dataset. These results surpass competing algorithms, demonstrating PGpocket’s advancement and practicality for protein–ligand binding site prediction.
Computational Analysis and Experimental Data Exploring the Role of Hesperetin in Ameliorating ADHD and SIRT1/Nrf2/Keap1/OH-1 Signaling
Authors: Mokhtar Hatem I. , Abd El-Fadeal Noha M. , El-Sayed Rehab M. , Hegazy Ann , El-Kherbetawy Mohamed K. , Hamad Ahmed G. , ElSayed Mohamed H. , Zaitone Sawsan A.
Published: August 2024

Attention deficit hyperactivity disorder (ADHD) manifests as poor attention, hyperactivity, as well as impulsive behaviors. Hesperetin (HSP) is a citrus flavanone with strong antioxidant and anti-inflammatory activities. The present study aimed to test hesperetin efficacy in alleviating experimental ADHD in mice and its influence on hippocampal neuron integrity and sirtuin 1 (SIRT1) signaling. An in silico study was performed to test the related proteins. Groups of mice were assigned as control, ADHD model, ADHD/HSP (25 mg/kg), and ADHD/HSP (50 mg/kg). ADHD was induced by feeding with monosodium glutamate (0.4 g/kg, for 8 weeks) and assessed by measuring the motor and attentive behaviors (open filed test, Y-maze test, and marble burying test), histopathological examination of the whole brain tissues, and estimation of inflammatory markers. The in-silico results indicated the putative effects of hesperetin on ADHD by allowing the integration and analysis of large-scale genomic, transcriptomic, and proteomic data. The in vivo results showed that ADHD model mice displayed motor hyperactivity and poor attention in the behavioral tasks and shrank neurons at various hippocampal regions. Further, there was a decline in the mRNA expression and protein levels for SIRT1, the erythroid 2-related factor-2 (Nrf2), kelch like ECH associated protein 1 (Keap1) and hemeoxygenase-1 (OH-1) proteins. Treatment with HSP normalized the motor and attentive behaviors, prevented hippocampal neuron shrinkage, and upregulated SIRT1/Nrf2/Keap1/OH-1 proteins. Taken together, HSP mainly acts by its antioxidant potential. However, therapeutic interventions with hesperetin or a hesperetin-rich diet can be suggested as a complementary treatment in ADHD patients but cannot be suggested as an ADHD treatment per se as it is a heterogeneous and complex disease.
FABP5 Is a Possible Factor for the Maintenance of Functions of Human Non-Pigmented Ciliary Epithelium Cells
Authors: Higashide Megumi , Watanabe Megumi , Sato Tatsuya , Umetsu Araya , Nishikiori Nami , Ogawa Toshifumi , Furuhashi Masato , Ohguro Hiroshi
Published: August 2024

To elucidate the possible biological roles of fatty acid-binding protein 5 (FABP5) in the intraocular environment, the cells from which FABP5 originates were determined by using four different intraocular tissue-derived cell types including human non-pigmented ciliary epithelium (HNPCE) cells, retinoblastoma (RB) cells, adult retinal pigment epithelial19 (ARPE19) cells and human ocular choroidal fibroblast (HOCF) cell lines, and the effects of FABP ligand 6, a specific inhibitor for FABP5 and FABP7 were analyzed by RNA sequencing and seahorse cellular metabolic measurements. Among these four different cell types, qPCR analysis showed that FABP5 was most prominently expressed in HNPCE cells, in which no mRNA expression of FABP7 was detected. In RNA sequencing analysis, 166 markedly up-regulated and 198 markedly down-regulated differentially expressed genes (DEGs) were detected between non-treated cells and cells treated with FABP ligand 6. IPA analysis of these DEGs suggested that FABP5 may be involved in essential roles required for cell development, cell survival and cell homeostasis. In support of this possibility, both mitochondrial and glycolytic functions of HNPCE cells, in which mRNA expression of FABP5, but not that of FABP7, was detected, were shown by using a Seahorse XFe96 Bioanalyzer to be dramatically suppressed by FABP ligand 6-induced inhibition of the activity of FABP5. Furthermore, in IPA upstream analysis, various unfolded protein response (UPR)-related factors were identified as upstream and causal network master regulators. Analysis by qPCR analysis showed significant upregulation of the mRNA expression of most of UPR-related factors and aquaporin1 (AQP1). The findings in this study suggest that HNPCE is one of intraocular cells producing FABP5 and may be involved in the maintenance of UPR and AQP1-related functions of HNPCE.
Single-Cell Transcriptomics Reveals Early Effects of Ionizing Radiation on Bone Marrow Mononuclear Cells in Mice
Authors: Wu Yun-Qiang , Ding Ke-Xin , Lv Zhi-Chun , Cao Zheng-Yue , Zhao Ke , Gao Hui-Ying , Sun Hui-Ying , Li Jing-Jing , Li Si-Yu , Zhao Xiong-Wei , Xue Yang , Xiang Shen-Si , Zheng Xiao-Fei , Yang Xiao-Ming , Li Chang-Yan
Published: August 2024

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte–macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.
Crucial Interactions between Altered Plasma Trace Elements and Fatty Acids Unbalance Ratio to Management of Systemic Arterial Hypertension in Diabetic Patients: Focus on Endothelial Dysfunction
Authors: Gouaref Ines , Otmane Amel , Makrelouf Mohamed , Abderrhmane Samir Ait , Haddam Ali El Mahdi , Koceir Elhadj-Ahmed
Published: August 2024

The coexistence of SAH with T2DM is a common comorbidity. In this study, we investigated the link between altered plasma antioxidant trace elements (ATE: manganese, selenium, zinc, and copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile, which is modified during SAH-T2DM association compared to the healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of total SFA, palmitic acid, arachidonic acid, and PUFA ω6/PUFA ω3; drop in tandem of PUFA/SFA and EPA + DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA rise, concurrent drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitant enhancement of Cu, Mn, and Fe); endothelial dysfunction (endotheline−1 increase); athero-thrombogenesis risk (concomitant rise of ApoB100/ApoA1, Ox-LDL, tHcy, and Lp(a)), and inflammation (higher of Hs-CRP, fibrinogen and ferritin). Our study opens to new therapeutic targets and to better dietary management, such as to establishing dietary ATE and PUFA ω6/PUFA ω3 or PUFA/SFA reference values for atherosclerotic risk prevention in hypertensive/diabetic patients.
Calprotectin, a Promising Serological Biomarker for the Early Diagnosis of Superinfections with Multidrug-Resistant Bacteria in Patients with COVID-19
Authors: Keller Dennis , Mester Patricia , Räth Ulrich , Krautbauer Sabrina , Schmid Stephan , Greifenberg Verena , Müller Martina , Kunst Claudia , Buechler Christa , Pavel Vlad
Published: August 2024

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.
Strategies to Maintain Redox Homeostasis in Yeast Cells with Impaired Fermentation-Dependent NADPH Generation
Authors: Kwolek-Mirek Magdalena , Maslanka Roman , Bednarska Sabina , Przywara Michał , Kwolek Kornelia , Zadrag-Tecza Renata
Published: August 2024

Redox homeostasis is the balance between oxidation and reduction reactions. Its maintenance depends on glutathione, including its reduced and oxidized form, GSH/GSSG, which is the main intracellular redox buffer, but also on the nicotinamide adenine dinucleotide phosphate, including its reduced and oxidized form, NADPH/NADP+. Under conditions that enable yeast cells to undergo fermentative metabolism, the main source of NADPH is the pentose phosphate pathway. The lack of enzymes responsible for the production of NADPH has a significant impact on yeast cells. However, cells may compensate in different ways for impairments in NADPH synthesis, and the choice of compensation strategy has several consequences for cell functioning. The present study of this issue was based on isogenic mutants: Δzwf1, Δgnd1, Δald6, and the wild strain, as well as a comprehensive panel of molecular analyses such as the level of gene expression, protein content, and enzyme activity. The obtained results indicate that yeast cells compensate for the lack of enzymes responsible for the production of cytosolic NADPH by changing the content of selected proteins and/or their enzymatic activity. In turn, the cellular strategy used to compensate for them may affect cellular efficiency, and thus, the ability to grow or sensitivity to environmental acidification.
Effects of UV-B and UV-C Spectrum Supplementation on the Antioxidant Properties and Photosynthetic Activity of Lettuce Cultivars
Authors: Skowron Ernest , Trojak Magdalena , Pacak Ilona
Published: August 2024

Indoor farming systems enable plant production in precisely controlled environments. However, implementing stable growth conditions and the absence of stress stimulants can weaken plants’ defense responses and limit the accumulation of bioactive, health-beneficial phytochemicals. A potential solution is the controlled application of stressors, such as supplemental ultraviolet (UV) light. To this end, we analyzed the efficiency of short-term pre-harvest supplementation of the red–green–blue (RGB, LED) spectrum with ultraviolet B (UV-B) or C (UV-C) light to boost phytochemical synthesis. Additionally, given the biological harm of UV radiation due to high-energy photons, we monitored plants’ photosynthetic activity during treatment and their morphology as well as sensory attributes after the treatment. Our analyses showed that UV-B radiation did not negatively impact photosynthetic activity while significantly increasing the overall antioxidant potential of lettuce through enhanced levels of secondary metabolites (total phenolics, flavonoids, anthocyanins), carotenoids, and ascorbic acid. On the contrary, UV-C radiation-induced anthocyanin accumulation in the green leaf cultivar significantly harmed the photosynthetic apparatus and limited plant growth. Taken together, we showed that short-term UV-B light supplementation is an efficient method for lettuce biofortification with healthy phytochemicals, while UV-C treatment is not recommended due to the negative impact on the quality (morphology, sensory properties) of the obtained leafy products. These results are crucial for understanding the potential of UV light supplementation for producing functional plants.
CRISPR/Cas9 Technology for Enhancing Desirable Traits of Fish Species in Aquaculture
Authors: Zhu Minli , Sumana Sahr Lamin , Abdullateef Mukhtar Muhammad , Falayi Opeoluwa Christiana , Shui Yan , Zhang Chengfeng , Zhu Jian , Su Shengyan
Published: August 2024

Aquaculture, the world’s fastest-growing food production sector, is critical for addressing food security concerns because of its potential to deliver high-quality, nutrient-rich supplies by 2050. This review assesses the effectiveness of CRISPR/Cas9 genome editing technology in enhancing desirable traits in fish species, including growth rates, muscle quality, disease resistance, pigmentation, and more. It also focuses on the potential effectiveness of the technology in allowing precise and targeted modifications of fish DNA to improve desirable characteristics. Many studies have reported successful applications of CRISPR/Cas9, such as knocking out reproductive genes to control reproduction and sex determination, enhancing feed conversion efficiency, and reducing off-target effects. Additionally, this technology has contributed to environmental sustainability by reducing nitrogen-rich waste and improving the nutritional composition of fish. However, the acceptance of CRISPR/Cas9 modified fish by the public and consumers is hindered by concerns regarding public perception, potential ecological impacts, and regulatory frameworks. To gain public approval and consumer confidence, clear communication about the editing process, as well as data on the safety and environmental considerations of genetically modified fish, are essential. This review paper discusses these challenges, provides possible solutions, and recommends future research on the integration of CRISPR/Cas9 into sustainable aquaculture practices, focusing on the responsible management of genetically modified fish to enable the creation of growth and disease-resistant strains. In conclusion, this review highlights the transformative potential of CRISPR/Cas9 technology in improving fish traits, while also considering the challenges and ethical considerations associated with sustainable and responsible practices in aquaculture.
Skin Improvement Effects of Ultrasound-Enzyme-Treated Collagen Peptide Extracts from Flatfish (Paralichthys olivaceus) Skin in an In Vitro Model
Authors: Eom Su-Jin , Kim Jae-Hoon , Ryu A-Reum , Park Heejin , Lee Jae-Hoon , Park Jung-Hyun , Lee Nam-Hyouck , Lee Saerom , Lim Tae-Gyu , Kang Min-Cheol , Song Kyung-Mo
Published: August 2024

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.
Comparative Analysis of the Fatty Acid Profiles of Selected Representatives of Chlorella-Clade to Evaluate Their Biotechnological Potential
Authors: Krivina Elena , Degtyaryov Evgeny , Tebina Elizaveta , Temraleeva Anna , Savchenko Tatyana
Published: August 2024

The objective of this study was to analyze the fatty acid composition of five strains from the genera Chlorella, Micractinium, and Meyerella and conduct an initial assessment of their biotechnological potential. It was found that the strain C. vulgaris VKM Al-335 is a good producer of palmitic acid, the Micractinium strains VKM Al-332 and VKM Al-343 are rich in ω-3 fatty acids, whereas the Meyerella strains VKM Al-346 and VKM Al-428 are producers of ω-6 fatty acids. A comparison of the biotechnological potential of algae with that of higher plant leaves (wheat) demonstrates that algal fatty acids exhibit greater diversity, although it is inferior to wheat leaves in terms of polyunsaturated and ω-3 fatty acids. Correlation analysis showed that when only straight-chain fatty acids were considered, the strains were distributed on the principal component analysis plot in accordance with their genetic relationships. However, when the entire fatty acid profile, inclusive of minor branched-chain and cyclic fatty acids, was analyzed, the algae distribution was in accordance with the environmental conditions in the original habitat, suggesting a possible connection between branched-chain and cyclic fatty acids and microalgae adaptability to environmental temperature conditions.
Research on Optimizing Human Resource Expenditure in the Allocation of Materials in Universities
Authors: Zhao Li , Wang Ying
Published: August 2024

This paper establishes a multivariate function model for natural human load-carrying walking in some typical scenarios such as college equipment and material relocation by students and a large amount of identical freight relocation in commercial activities. For classified material relocation needs and constraints, we obtain the relationship between walking speed and load weight for a single person, as well as the time cost for different round trips. By establishing an integer programming model with the minimum total transportation time cost and shelf life as the objective function and the requirements of negative weight and speed as the constraint conditions, we reach the optimal item allocation methods considering time cost and shelf life. We discover that there is an approximate linear relationship between the change in natural walking speed and travel time when the load is small, thus obtaining the time cost of student transportation under different round-trip situations. The Monte Carlo simulation algorithm, which is more efficient compared with other methods such as the integer programming method, is used to obtain the optimal allocation scheme that meets the efficiency and quality requirements. The analysis methods and results can be used as guidance for task scheduling optimization for material relocation in educational organizations as well as commercial agencies.
Computational Analysis of Marker Genes in Alzheimer’s Disease across Multiple Brain Regions
Authors: Karanikolaos Panagiotis , Krokidis Marios G. , Exarchos Themis P. , Vlamos Panagiotis
Published: August 2024

Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia in the elderly, which is characterized by progressive cognitive impairment. Herein, we undertake a sophisticated computational analysis by integrating single-cell RNA sequencing (scRNA-seq) data from multiple brain regions significantly affected by the disease, including the entorhinal cortex, prefrontal cortex, superior frontal gyrus, and superior parietal lobe. Our pipeline combines datasets derived from the aforementioned tissues into a unified analysis framework, facilitating cross-regional comparisons to provide a holistic view of the impact of the disease on the cellular and molecular landscape of the brain. We employed advanced computational techniques such as batch effect correction, normalization, dimensionality reduction, clustering, and visualization to explore cellular heterogeneity and gene expression patterns across these regions. Our findings suggest that enabling the integration of data from multiple batches can significantly enhance our understanding of AD complexity, thereby identifying key molecular targets for potential therapeutic intervention. This study established a precedent for future research by demonstrating how existing data can be reanalysed in a coherent manner to elucidate the systemic nature of the disease and inform the development of more effective diagnostic tools and targeted therapies.
Phytate Effects on Incomplete Distal Renal Tubular Acidosis
Authors: Guimerà Jordi , Martínez Ana , Quetglas José Luis Bauzá , Sanchis Pilar , Costa-Bauzá Antonia , Pieras Enrique , Grases Felix
Published: August 2024

Background: Adults who have incomplete distal renal tubular acidosis (dRTA) may present with recurrent urolithiasis due to metabolic acidosis, leading to bone resorption, which in turn causes hypercalciuria and urine alkalinization (pH > 6.0). Oral potassium citrate is the most commonly used treatment for dRTA, but some patients cannot tolerate this treatment. The objective of this single-arm study was to evaluate the effect of phytate, an inhibitor of bone resorption, on calciuria of patients with incomplete dRTA. Methods: The calciuria levels of 16 patients who had incomplete dRTA with urolithiasis and could not tolerate potassium citrate treatment were recorded before (baseline) and after 6 months of treatment with oral calcium magnesium phytate (380 mg every 12 h). There were no dietary modifications or other treatments. Results: The baseline calciuria was 317 ± 81 mg/24 h and the level after 6 months was 221 ± 38 mg/24 h (p < 0.005). Conclusions: Our results suggest that calcium magnesium phytate should be considered as an alternative or adjunctive treatment for hypercalciuria in patients with incomplete dRTA.
Atherosclerosis Prevalence among Different Physical Activity Patterns in Adult Men
Authors: Perez-Lasierra Jose Luis , Casajús Jose Antonio , Gonzalez-Agüero Alejandro , Casasnovas Jose Antonio , Torrijo-Blanche Carolina , Gimeno-Ruiz Sofia , Moreno-Franco Belén
Published: August 2024

Background: Physical activity (PA) intensity could play a key role in atherosclerosis risk, but the existing literature shows controversial results. The aim of this study was to analyze the association of different PA levels with the presence of subclinical atherosclerosis in femoral and carotid arteries. Methods: A cross-sectional analysis was conducted of 449 middle-aged men belonging to the Aragon Workers’ Health Study. Demographic, anthropometric, and clinical data were obtained during the annual medical examination. Ultrasonography was used to assess the presence of atheroma plaques in femoral and carotid territories. Accelerometry was used to assess habitual PA. Participants were categorized into vigorous PA (VPA) groups (0 min/week, >0–60 min/week, >60 min/week), and into moderate to vigorous PA (MVPA) groups using terciles as cut-offs. Results: Compared with participants who completed 0 min/week of VPA, those participants who completed >60 min/week of VPA had fully adjusted odds of subclinical atherosclerosis of 0.47 (95%CI: 0.22, 0.99, p < 0.05) and 0.35 (95%CI: 0.17, 0.73, p < 0.05) for femoral and any territory (femoral and/or carotid) respectively. No significant differences were observed in the prevalence of atheroma plaques in any vascular territory between the different MVPA groups. Conclusions: Performing more than 60 min/week of VPA is associated with reduced odds for subclinical atherosclerosis in femoral or any vascular territory in adult men.
A Comprehensive Characterization of Patients with Spinal Cord Neurosarcoidosis: A Single Center Cross-Sectional Study of Clinical Outcomes
Authors: Al-Hader Rami , Nofar Justin , Mohamedelkhair Ahmed , Affan Muhammad , Schultz Lonni R. , Cerghet Mirela
Published: August 2024

Background/Objective: To describe the clinical features and radiological outcomes of patients with spinal cord neurosarcoidosis, treatments, and long-term follow-up for this rare disorder. Methods: A cross-sectional, retrospective medical chart review was performed for all patients with spinal cord neurosarcoidosis treated at a single center between 01/1995 and 12/2020. Radiological imaging, laboratory test results, the type of immunosuppressive therapy, and function test scores were reviewed. Results: We assessed 39 patients with spinal cord neurosarcoidosis (23 men, 16 women, mean age at presentation 46.4 years, SD 10.2 years). The mean (SD) duration of spinal cord neurosarcoidosis at data abstraction was 9.8 (6.3) years. There were 24 patients (62%) with extensive intramedullary lesions, 8 (21%) with multiple patchy intramedullary lesions, 12 (31%) with leptomeningeal involvement, and 7 (18%) with nerve root enhancement. The cervical spine was the most commonly affected region in 33 patients (85%). The most common presenting symptoms were paresthesia/neuropathic pain in 20 (51%) and weakness of extremities in 15 (38%) patients. Most patients (n = 37; 95%) had been treated with corticosteroids at symptom onset, and methotrexate was the most used immunosuppressive therapy (n = 19; 49%). Of 34 patients with follow-up magnetic resonance imaging (MRI) available, the median time to improvement per MRI was 10.8 months (95% CI, 6.1–17.0 months). Of 31 patients with MRI enhancement at presentation, 18 (58%) had complete enhancement resolution at follow-up, with a median time to resolution of 51.8 months (95% CI, 24.9–83.4 months). Patients had significantly lower pyramidal (p = 0.004) and sensory functional (p = 0.031) systems scores from presentation to the last clinic visit. Conclusions: Because spinal cord neurosarcoidosis is challenging to diagnose and no set treatment guidelines exist, clarifying patients’ clinical parameters and responses to various treatments is needed to improve timely and efficient care. The incidence of spinal cord involvement in sarcoidosis in our cohort was higher than intracranial involvement and most patients had a long extensive intramedullary lesion. We also observed that most patients with spinal cord neurosarcoidosis improved clinically and radiologically after treatment; however, the resolution of MRI enhancement after immunosuppressive therapy may take years. Prospective studies of neurosarcoidosis will be crucial to address questions about effective treatment and long-term prognosis.