bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Inflammation on the Etiopathogenesis of Benign Salivary Gland Tumors: A Scoping Review
Authors: Szydłowski Konrad , Puchalski Michał , Ołdziej Stanisław , Kasprzyk-Tryk Agnieszka , Skorek Andrzej , Tretiakow Dmitry
Published: November 2024

Salivary gland tumors are rare head and neck tumors constituting up to 6% of all head and neck neoplasms; despite being mostly benign, these tumors present in diverse histological subtypes, making them challenging to diagnose and treat. Our research aims to investigate the link between inflammation and tumorigenesis within the salivary glands based on the literature regarding the etiopathogenesis of benign salivary gland tumors. This scoping review was conducted following the PRISMA extension for scoping reviews and reporting guidelines. The search was conducted using the Pubmed and Embase databases. Articles published between 2004 and May 2024 were included in the review. A total of 1097 papers were collected and identified. After 271 duplicates were removed, 826 titles and abstracts were independently reviewed by two researchers. Based on the title and abstract, 735 citations were excluded, and 91 articles were assessed for eligibility. Data were extracted from 46 articles that met the inclusion criteria. The review highlights the significance of inflammation-related factors and its relations with benign salivary gland tumors (SGTs). Knowledge of the etiopathogenesis of these tumors remains insufficient, and their rich immunological background poses challenges in diagnosis. The findings also point to directions for further clinical research, which will be necessary to implement these molecules in clinical practice.
Activation of Purinergic P2Y2 Receptor Protects the Kidney Against Renal Ischemia and Reperfusion Injury in Mice
Authors: Jeong Kyuho , Je Jihyun , Dusabimana Theodomir , Karekezi Jacques , Nugroho Tatang Aldi , Ndahigwa Edvard Ntambara , Yun Seung Pil , Kim Hye Jung , Kim Hwajin , Park Sang Won
Published: November 2024

Extracellular ATP plays an important role in renal physiology as well as the pathogenesis of acute kidney injury induced by renal ischemia and reperfusion (IR). Expression of the purinergic P2Y2 receptor has been shown on inflammatory and structural cells of the kidney, and P2Y2R is preferably activated by ATP (or UTP). Here, we investigated the molecular mechanism of P2Y2R during IR injury by using P2Y2R knockout (KO) mice and a selective P2Y2R agonist, MRS2768. After renal IR, P2Y2R KO mice showed greater increases in plasma creatinine, tubular damage and neutrophil infiltration, and significant induction of proinflammatory cytokines and apoptotic markers than wild-type (WT) mice. In contrast, treatment with MRS2768 reduced plasma creatinine levels, tubular damage and inflammation, and renal apoptosis in mice subjected to renal IR. In cultured human proximal tubular HK-2 cells, MRS2768 upregulated P2Y2R mRNA levels and decreased TNF-α/cycloheximide-induced apoptosis and inflammation. Importantly, P2Y2R activation by MRS2768 increased the phosphorylation of protein kinase C (PKC), Src, and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, the inhibition of PI3K/Akt abolished the protective effects of MRS2768 against TNF-α/cycloheximide-induced apoptosis and inflammation in HK-2 cells. In conclusion, activation of P2Y2R protects against tubular apoptosis and inflammation during renal IR via the PKC/Src/Akt pathway, suggesting P2Y2R is a promising therapeutic target for acute kidney injury.
Photocrosslinkable Biomaterials for 3D Bioprinting: Mechanisms, Recent Advances, and Future Prospects
Authors: Lai Yushang , Xiao Xiong , Huang Ziwei , Duan Hongying , Yang Liping , Yang Yuchu , Li Chenxi , Feng Li
Published: November 2024

Constructing scaffolds with the desired structures and functions is one of the main goals of tissue engineering. Three-dimensional (3D) bioprinting is a promising technology that enables the personalized fabrication of devices with regulated biological and mechanical characteristics similar to natural tissues/organs. To date, 3D bioprinting has been widely explored for biomedical applications like tissue engineering, drug delivery, drug screening, and in vitro disease model construction. Among different bioinks, photocrosslinkable bioinks have emerged as a powerful choice for the advanced fabrication of 3D devices, with fast crosslinking speed, high resolution, and great print fidelity. The photocrosslinkable biomaterials used for light-based 3D printing play a pivotal role in the fabrication of functional constructs. Herein, this review outlines the general 3D bioprinting approaches related to photocrosslinkable biomaterials, including extrusion-based printing, inkjet printing, stereolithography printing, and laser-assisted printing. Further, the mechanisms, advantages, and limitations of photopolymerization and photoinitiators are discussed. Next, recent advances in natural and synthetic photocrosslinkable biomaterials used for 3D bioprinting are highlighted. Finally, the challenges and future perspectives of photocrosslinkable bioinks and bioprinting approaches are envisaged.
Somatic Recombination Between an Ancient and a Recent NOTCH2 Gene Variant Is Associated with the NOTCH2 Gain-of-Function Phenotype in Chronic Lymphocytic Leukemia
Authors: Hubmann Rainer , Hilgarth Martin , Löwenstern Tamara , Lienhard Andrea , Sima Filip , Reisinger Manuel , Hobel-Kleisch Claudia , Porpaczy Edit , Haferlach Torsten , Hoermann Gregor , Laccone Franco , Jungbauer Christof , Valent Peter , Staber Philipp B. , Shehata Medhat , Jäger Ulrich
Published: November 2024

Constitutively active NOTCH2 signaling is a hallmark in chronic lymphocytic leukemia (CLL). The precise underlying defect remains obscure. Here we show that the mRNA sequence coding for the NOTCH2 negative regulatory region (NRR) is consistently deleted in CLL cells. The most common NOTCH2ΔNRR-DEL2 deletion is associated with two intronic single nucleotide variations (SNVs) which either create (CTTAT, G>A for rs2453058) or destroy (CTCGT, A>G for rs5025718) a putative splicing branch point sequence (BPS). Phylogenetic analysis demonstrates that rs2453058 is part of an ancient NOTCH2 gene variant (*1A01) which is associated with type 2 diabetes mellitus (T2DM) and is two times more frequent in Europeans than in East Asians, resembling the differences in CLL incidence. In contrast, rs5025718 belongs to a recent NOTCH2 variant (*1a4) that dominates the world outside Africa. Nanopore sequencing indicates that somatic reciprocal crossing over between rs2453058 (*1A01) and rs5025718 (*1a4) leads to recombined NOTCH2 alleles with altered BPS patterns in NOTCH2*1A01/*1a4 CLL cases. This would explain the loss of the NRR domain by aberrant pre-mRNA splicing and consequently the NOTCH2 gain-of-function phenotype. Together, our findings suggest that somatic recombination of inherited NOTCH2 variants might be relevant to CLL etiology and may at least partly explain its geographical clustering.
The Current Status and Prospects of the Application of Omics Technology in the Study of Ulmus
Authors: Wang Shijie , Zuo Lihui , Liu Yichao , Long Lianxiang , Jiang Min , Han Mengjuan , Wang Jinmao , Yang Minsheng
Published: November 2024

Elm (Ulmus) species are important components of forest resources with significant ecological and economic value. As tall hardwood trees that are drought-resistant, poor-soil-tolerant, and highly adaptable, Ulmus species are an excellent choice for ecologically protected forests and urban landscaping. Additionally, the bioactive substances identified in the fruits, leaves, bark, and roots of Ulmus have potential applications in the food and medical fields and as raw materials in industrial and cosmetic applications. However, the survival of Ulmus species in the natural environment has been threatened by recurrent outbreaks of Dutch elm disease, which have led to the death of large numbers of Ulmus trees. In addition, severe damage to the natural habitats of some Ulmus species is driving their populations to extinction. Omics technology has become an important tool for the collection, protection, and biological characteristic analysis of Ulmus species and their resources due to its recent advances. This article summarizes the current research and application status of omics technology in Ulmus. The remaining problems are noted, and future research directions are proposed. Our review is aimed at providing a reference for resource conservation of Ulmus and for scientific research into this genus.
Marine Peptides: Potential Basic Structures for the Development of Hybrid Compounds as Multitarget Therapeutics for the Treatment of Multifactorial Diseases
Authors: Bauer Marta , Glowacka Magdalena , Kamysz Wojciech , Kleczkowska Patrycja
Published: November 2024

Marine-derived peptides display potent antihypertensive, antioxidant, analgesic and antimicrobial biological effects. Some of them have also been found to have anticancer activity via various mechanisms differing from those of continental organisms. This diversity of properties—together with the peptides’ efficacy, which has been confirmed in several in vitro and in vivo studies—make these compounds attractive as functional ingredients in pharmacy, especially in regard to multitarget drugs known as hybrids. Given the possibilities offered by chimeric structures, it is expected that a hybridization strategy based on a marine-derived compound could result in a long-awaited success in the development of new effective compounds to combat a range of complex diseases. However, despite the fact that the biological activity of such new hybrids may exceed that of their parent compounds, there is still an urgent need to carefully determine their potential off-targets and thus possible clinically important side effects. Given the above, the aim of this paper is to provide information on compounds of marine origin with peptide structures and to verify the occurrence and usage of hybrid compounds built from these structures. Furthermore, the authors believe that information presented here will serve to increase public awareness of the new opportunities arising from the combination of hybridization strategies with marine molecules with known structures and biological properties, thereby accelerating the development of effective drug candidates.
A Brief Overview of Ethanol Tolerance and Its Potential Association with Circadian Rhythm in Drosophila
Authors: Peterson Sophie K. , Ahmad S. Tariq
Published: November 2024

Alcohol consumption and addiction remain global health concerns, with significant loss of productivity, morbidity, and mortality. Drosophila melanogaster, a widely used model organism, offers valuable insights into the genetic and neuronal mechanisms underlying ethanol-induced behaviors (EIBs) such as sedation, recovery, and tolerance. This narrative review focuses on studies in the Drosophila model system suggesting an association between circadian rhythm genes as modulators of ethanol tolerance. Mutations in these genes disrupt both the circadian cycle and tolerance, underscoring the interplay between circadian rhythm and ethanol processing although the exact mechanisms remain largely unknown. Additionally, genes involved in stress response, gene expression regulation, neurotransmission, and synaptic activity were implicated in ethanol tolerance modulation. At the neuronal level, recent studies have highlighted the involvement of corazonin (CRZ) and neuropeptide F (NPF) neurons in modulating EIBs. Understanding the temporal dynamics of tolerance development is crucial for describing the molecular basis of ethanol tolerance. Ultimately, insights gained from Drosophila studies hold promise for elucidating the neurobiological underpinnings of alcohol use disorders and addiction, contributing to more effective interventions and treatments.
PTH1R Suppressed Apoptosis of Mesenchymal Progenitors in Mandibular Growth
Authors: Cui Chen , Lu Chuang , Cai Yanling , Xiong Yuhua , Duan Yihong , Lan Kaiwen , Fan Yi , Zhou Xuedong , Wei Xi
Published: November 2024

Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood. Here, we report that mice with deletion of PTH1R in Prx1-positive mesenchymal cells (Prx1Cre;PTH1Rfl/fl) exhibit decreased alveolar bone mass due in part to apoptotic response activation. The exploration of oral bone-derived mesenchymal stem cells (OMSCs) with PTH1R deficiency suggests PTH1R signaling modulates OMSCs’ apoptosis by interfering mitochondrial function and morphology. The underlying molecular mechanisms are studied by transcriptome sequencing analysis, finding that inositol trisphosphate receptor-3 (IP3R-3), an endoplasmic reticulum calcium channel protein, serves as a modulator of pro-apoptosis in OMSCs. Furthermore, we find PTH1R and its downstream protein kinase A (PKA) pathway dampen IP3R-3’s expression. Of note, OMSCs with IP3R-3 overexpression recapitulate the PTH1R-deletion phenotypes, while IP3R-3 silence rescues mitochondrial dysfunction. Altogether, our study uncovers the anti-apoptotic function of PTH1R signaling in OMSCs and proves that excess apoptosis partly contributes to a weakening potential of osteogenic differentiation and aberrant mandibular development.
The Effect of CBM1 and Linker on the Oxidase, Peroxidase and Monooxygenase Activities of AA9 LPMOs: Insight into Their Correlation with the Nature of Reductants and Crystallinity of Celluloses
Authors: Zhao Xu , Xie Fei , Chen Kaixiang , Long Liangkun , Ding Shaojun
Published: November 2024

This study explores the effect of carbohydrate-binding module 1 (CBM1) and the linker on the function of auxiliary activity 9 (AA9) lytic polysaccharide monooxygenases (LPMOs), with a particular focus on monooxygenase activity, using different crystallinity celluloses and electron donors. The tested C1/C4-oxidizing AA9 LPMOs exhibited higher oxidase and peroxidase activities compared to those of the C4-oxidizing AA9 LPMOs. While the presence of CBM1 promoted cellulose-binding affinity, it reduced the oxidase activity of modular AA9 LPMOs. The effect of CBM1 on peroxidase activity was variable and enzyme-specific. Its influence on monooxygenase activity was linked to the type of reductants and the crystallinity of celluloses. Overall, CBM1 improved the monooxygenase activity on high-, medium-, and low-crystallinity celluloses when ascorbic acid (AscA) was used as the electron donor. CBM1 also facilitated monooxygenase activity on high-crystallinity cellulose, but significantly inhibited monooxygenase activity on low-crystallinity cellulose when cellobiose dehydrogenase (CDH) was the electron donor. Linker truncation of NcLOMO9C enhanced the cellulose-binding affinity but decreased both the oxidase and peroxidase activities. Linker truncation also impacted the monooxygenase activity in both the AscA-AA9 LPMO and AfCDH-AA9 LPMO systems, though its effect was less pronounced compared to that of CBM1. This work provides new insights into the role of the reductant type and cellulose crystallinity in the functionality of CBM1 and the linker in AA9 LPMOs.
The Effect of Prostaglandin F2 Analog Treatment on the Immunoexpression of Fibrosis-Associated Factors in Patients with Glaucoma Undergoing Deep Sclerotomy
Authors: Stanić Robert , Vukojević Katarina , Filipović Natalija , Benzon Benjamin , Ogorevc Marin , Kunac Nenad , Čanović Samir , Kovačević Petra , Paradžik Šimunović Martina , Konjevoda Suzana
Published: November 2024

Long-term use of topical prostaglandins might initiate chronic conjunctival inflammation, leading to poor outcomes of glaucoma surgery. The aim of this study was to evaluate the immunoexpression pattern of HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa in the conjunctiva, episclera, and deep sclera in patients with glaucoma undergoing deep sclerectomy in order to establish an association between staining intensities and prostaglandin F2 (PGF2) treatment. Double immunofluorescence (HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa) was performed on conjunctiva, episclera, and deep sclera samples, which were obtained from 23 patients treated with PGF2 and 8 patients without PGF2 treatment. When comparing the ocular tissues of patients regarding treatment with PGF2 analogs, we found a significant increase in the immunoexpression of HSP70 in the conjunctival epithelium of patients treated with PGF2 analogs compared to those without PGF2 treatment. These patients also had an increase in SNAIL immunoexpression and a decrease in aSMA immunoexpression in the deep sclera. There were no significant differences in HIFa, CTGF, or cMYB immunoexpression levels between the two groups. Further research into the regulation of these factors in ocular tissues could lead to the development of potential novel therapeutic approaches in glaucoma management.
The circRNA Landscape in Recurrent Pregnacy Loss (RPL): A Comparison of Four Reproductive Tissues
Authors: Varela-Martínez Endika , Colau Olaia , van der Molen Renate G. , Jugo Begoña M.
Published: November 2024

Recurrent Pregnancy Loss (RPL), also named Recurrent Spontaneous Abortion (RSA), is a common fertility problem that refers to at least two consecutive pregnancy losses and affects 1–2% of couples all over the world. Despite common causes such as genetic abnormalities, uterine anomalies or hormonal and metabolic disorders, there is still a huge challenge in identifying the causes of about 40–60% of RPL patients. Circular RNAs (circRNAs) are endogenous ncRNAs with a unique closed-loop and single-stranded structure. Accumulated evidence indicates the role of circRNAs in embryonic development and implantation, which may help decipher the mechanisms and causes underlying RSA. Four works were selected in the SRA public repository that used RNAseq analysis in control and RPL samples in four tissues: endometrium, chorionic villus tissue, decidua and decidua immune cells. Two programs were selected for circRNA detection: DCC and CIRI2. A total of 1715 candidate circRNAs were detected after filtering the results. In the differential expression analysis, decidual tissue showed the highest percentage of circRNA with differential expression between cases and controls. CircRNAs originating from genes OGA, FNDC3B, RAB11FIP1, SIPA1L2 and GREB1L showed the highest expression in women suffering from pregnancy losses, in decidual tissue or endometrium. In the GO term enrichment analysis, multiple terms related to embryonic development and immunological response were consistently enriched in villus and decidual tissues. Although some differentially expressed circRNAs were shared between tissues, decidua seems the tissue of choice for analyzing the role of circRNAs in RPL.
Unravelling the Signature Follicular Fluid Metabolites in Dairy Cattle Follicles Growing Under Negative Energy Balance: An In Vitro Approach
Authors: Shahzad Muhammad , Cao Jianhua , Kolachi Hubdar Ali , Ayantoye Jesse Oluwaseun , Yu Zhou , Niu Yifan , Wan Pengcheng , Zhao Xueming
Published: November 2024

The astringent selection criteria for milk-oriented traits in dairy cattle have rendered these animals prone to various metabolic disorders. Postpartum lactational peak and reduced feed intake lead to negative energy balance in cattle. As a compensatory mechanism, cattle start mobilizing fat reserves to meet the energy demand for vital body functions. Consequently, diminished glucose concentrations and elevated ketone body levels lead to poor ovarian function. The impaired follicular development and subpar oocyte quality diminish the conception rates, which poses significant economic repercussions. Follicular fluid is integral to the processes of follicular growth and oocyte development. Hence, the present study was performed to identify potential alterations in metabolites in the follicular fluid under in vitro culture conditions mimicking negative energy balance. Our results revealed nine distinct metabolites exhibiting differential expression in follicular fluid under negative energy balance. The differentially expressed metabolites were predominantly associated with pathways related to amino acid metabolism, lipid metabolism, signal transduction mechanisms, and membrane transport, alongside other biological processes. The identified signature metabolites may be further validated to determine oocyte fitness subjected to in vitro fertilization or embryo production from slaughterhouse source ovaries.
Lipidomics of Caco-2 Cells Under Simulated Microgravity Conditions
Authors: Tolle Giulia , Serreli Gabriele , Deiana Monica , Moi Loredana , Zavattari Patrizia , Pantaleo Antonella , Manis Cristina , El Faqir Mohammed Amine , Caboni Pierluigi
Published: November 2024

Microgravity may profoundly impact the cardiovascular system, skeletal muscle system, and immune system of astronauts. At the cellular level, microgravity may also affect cell proliferation, differentiation, and growth, as well as lipid metabolism. In this work, we investigated lipid changes in Caco-2 cells cultured in a clinostat for 24 h under simulated microgravity conditions (SMC). Complex lipids were measured using a UHPLC-QTOF/MS platform, and the data were subjected to multivariate analysis. Under SMC, levels of ceramides Cer 18:0;O2/16:0, Cer 18:1;O2/16:0, Cer 18:1; O2/22:0, Cer 18:1;O2/24:0, and Cer 18:2;O2/24:0 were found to be upregulated, while sphingomyelins SM 16:1;O2/16:0, SM 16:1;O2/18:1, SM 18:1;O2/24:0, and SM 18:2;O2/24:0 were found to be downregulated. On the other hand, considering that sphingolipids are involved in the process of inflammation, we also treated Caco-2 cells with dextran sodium sulfate (DSS) to induce cell inflammation and lipopolysaccharide (LPS) to induce cell immune responses. As a result, we observed similar lipid dysregulation, indicating that SMC may exert a condition similar to inflammation. Our lipidomics strategy provides new insights into the altered metabolic pathway of ceramides and sphingomyelins of Caco-2 cells under SMC.
Exploring the Replication and Pathogenic Characteristics of Alpha, Delta, and Omicron Variants of SARS-CoV-2
Authors: Khan Sakirul , Yahiro Takaaki , Kimitsuki Kazunori , Hashimoto Takehiro , Matsuura Keiko , Yano Shinji , Noguchi Kazuko , Sonezaki Akane , Yoshizawa Kaori , Kumasako Yoko , Akbar Sheikh Mohammad Fazle , Nishizono Akira
Published: November 2024

The variants of concern (VOCs) of SARS-CoV-2 have exhibited different phenotypic characteristics in clinical settings which are yet to be fully explored. This study aimed to characterize the viral replication features of major VOCs of SARS-CoV-2 and their association with pathogenicity. The Alpha, Delta, and Omicron variants of SARS-CoV-2 isolated from the COVID-19 patients in Japan were propagated in VeroE6/TMPRSS2 cells. The viral replication and pathological features were evaluated by laser and electron microscopy at different time points. The results revealed that the Delta variant dominantly infected the VeroE6/TMPRSS2 cells and formed increased syncytia compared to the Alpha and Omicron variants. Relatively large numbers of virions and increased immunoreactivities of the SARS-CoV-2 N-protein were detected in the endoplasmic reticulum and intracellular vesicles of Delta-infected cells. Interestingly, the N-protein and virions were detected in the nucleus of Delta-infected cells, while such properties were not observed in the case of Alpha and Omicron variants. In addition, early nuclear membrane damage followed by severe cellular damage was prominent in Delta-infected cells. A unique mutation (G215C) in the N-protein of the Delta variant is thought to be associated with severe cell damage. In conclusion, this study highlights the distinct replicative and pathogenic characteristics of the Delta variant of SARS-CoV-2 compared to the Alpha and Omicron variants, shedding light on the potential mechanisms underlying its increased pathogenicity.
Trehalose Alleviates D-Galactose-Induced Aging-Related Granulosa Cell Death in Ovaries
Authors: Xi Huaming , Chen Xinyu , Liang Kai , Wang Xianglong , Jiang Feng , Li Yuan , Niu Dong
Published: November 2024

Ovarian dysfunction caused by aging restricts female reproductive capacity and is accompanied by oxidative stress and impaired autophagy. Recent studies have shown that trehalose (Tre) can activate autophagy and have antioxidant effects. However, whether Tre can be used to attenuate ovarian aging remains unclear. Therefore, the anti-aging effects of Tre on the ovary were explored both in vivo and in vitro. D-galactose (D-gal) was administered i.p. daily (200 mg/kg body weight) for 8 weeks to establish the mouse ovarian aging model (n = 10). We found that Tre significantly reversed ovarian weight loss and reduced the number of TUNEL-positive granulosa cells caused by D-gal in mouse ovaries. Tre elevated the protein expression levels of LC3-II, Parkin, PINK1, Beclin1, and LAMP2 in ovaries. Mitochondrial-related proteins TOM20 and COX IV expression levels were increased by Tre administration. In vitro studies further supported these findings, showing that Tre treatment significantly reduced the number of SA-β-gal and PI-positive cells, and decreased ROS levels in cultured granulosa cells. Thus, Tre alleviates ovarian aging by activating mitophagy and reducing oxidative stress, suggesting its potential as an anti-aging agent for ovarian health.
Spent Brewer’s Yeast Lysis Enables a Best Out of Waste Approach in the Beer Industry
Authors: Ciobanu Livia Teodora , Constantinescu-Aruxandei Diana , Farcasanu Ileana Cornelia , Oancea Florin
Published: November 2024

Yeasts have emerged as an important resource of bioactive compounds, proteins and peptides, polysaccharides and oligosaccharides, vitamin B, and polyphenols. Hundreds of thousands of tons of spent brewer’s yeast with great biological value are produced globally by breweries every year. Hence, streamlining the practical application processes of the bioactive compounds recovered could close a loop in an important bioeconomy value-chain. Cell lysis is a crucial step in the recovery of bioactive compounds such as (glyco)proteins, vitamins, and polysaccharides from yeasts. Besides the soluble intracellular content rich in bioactive molecules, which is released by cell lysis, the yeast cell walls β-glucan, chitin, and mannoproteins present properties that make them good candidates for various applications such as functional food ingredients, dietary supplements, or plant biostimulants. This literature study provides an overview of the lysis methods used to valorize spent brewer’s yeast. The content of yeast extracts and yeast cell walls resulting from cellular disruption of spent brewer’s yeast are discussed in correlation with the biological activities of these fractions and resulting applications. This review highlights the need for a deeper investigation of molecular mechanisms to unleash the potential of spent brewer’s yeast extracts and cell walls to become an important source for a variety of bioactive compounds.
Technology Innovation for Discovering Renal Autoantibodies in Autoimmune Conditions
Authors: Bruschi Maurizio , Candiano Giovanni , Petretto Andrea , Angeletti Andrea , Meroni Pier Luigi , Prunotto Marco , Ghiggeri Gian Marco
Published: November 2024

Autoimmune glomerulonephritis is a homogeneous area of renal pathology with clinical relevance in terms of its numerical impact and difficulties in its treatment. Systemic lupus erythematosus/lupus nephritis and membranous nephropathy are the two most frequent autoimmune conditions with clinical relevance. They are characterized by glomerular deposition of circulating autoantibodies that recognize glomerular antigens. Technologies for studying renal tissue and circulating antibodies have evolved over the years and have culminated with the direct analysis of antigen–antibody complexes in renal bioptic fragments. Initial studies utilized renal microdissection to obtain glomerular tissue. Obtaining immunoprecipitates after partial proteolysis of renal tissue is a recent evolution that eliminates the need for tissue microdissection. New technologies based on ‘super-resolution microscopy’ have added the possibility of a direct analysis of the interaction between circulating autoantibodies and their target antigens in glomeruli. Peptide and protein arrays represent the new frontier for identifying new autoantibodies in circulation. Peptide arrays consist of 7.5 million aligned peptides with 16 amino acids each, which cover the whole human proteome; protein arrays utilize, instead, a chip containing structured proteins, with 26.000 overall. An example of the application of the peptide array is the discovery in membranous nephropathy of many new circulating autoantibodies including formin-like-1, a protein of podosomes that is implicated in macrophage movements. Studies that utilize protein arrays are now in progress and will soon be published. The contribution of new technologies is expected to be relevant for extending our knowledge of the mechanisms involved in the pathogenesis of several autoimmune conditions. They may also add significant tools in clinical settings and modify the therapeutic handling of conditions that are not considered to be autoimmune.
Functional Characterization of Plant Peptide-Containing Sulfated Tyrosine (PSY) Family in Wheat (Triticum aestivum L.)
Authors: Zhang Peipei , Gao Weidong , Guo Lijian , Chen Ming , Ma Jingfu , Tian Tian , Wang Yanjie , Zhang Xiwei , Wei Yongtong , Chen Tao , Yang Delong
Published: November 2024

The plant peptide-containing sulfated tyrosine (PSY) family plays critical roles in plant cell proliferation and stress responses. However, the functional characterization of the PSY peptide family in wheat remains unclear. This study systematically identified a total of 29 TaPSY genes at the genome-wide level, classifying them into six subgroups based on PSY-like motifs. These peptides contain a highly conserved active peptide domain, closely resembling the Arabidopsis AtPSY1 motif. All TaPSY homologs are predicted to have a sulfated tyrosine catalyzed by plant tyrosylprotein sulfotransferase (TPST). The TaPSY genes displayed distinct expression patterns across various tissues, with most genes showing higher expression levels in roots and stems. Synthetic sulfated TaPSY peptides enhanced root growth in both wild-type Arabidopsis and the tpst-1 mutant plants. In wheat, exogenous application of TaPSY peptides also promoted root growth, with the synthetic TaPSY5 peptide affecting reactive oxygen species levels in wheat taproots to stimulate primary root growth. Furthermore, transgenic Arabidopsis plants overexpressing TaPSY10 exhibited longer primary roots and increased lateral root numbers. These findings provide insights into the physiological roles of TaPSY peptides in regulating wheat root growth.
Tissue Biomarkers in Gastric Cancer Treatment: Present and Future
Authors: Airò Giulia , Agnetti Virginia , Pratticò Fabiana , Peroni Marianna , Bui Simona , Mura Giovanni , Urbanowicz-Nijaki Maria , Lai Eleonora , Puzzoni Marco , Contu Fabiana , Denaro Nerina , Scartozzi Mario , Solinas Cinzia , Tommasi Chiara
Published: November 2024

The aggressive nature of gastric cancer often leads to late diagnosis and poor prognosis. Chemotherapy and the more recently added immunotherapy remain key treatments for this disease. Several studies have focused on identifying tissue biomarkers with prognostic and/or predictive roles and therefore the therapeutic options are rapidly growing. In this narrative review, we summarize the major tissue biomarkers routinely assessed in clinical practice. In addition, we focus on new evidence about emerging tissue biomarkers that could have a predictive role in future therapeutic approaches and also on the potential role of liquid biopsy in this neoplasm.
Shaping the Landscape of Lung Cancer: The Role and Therapeutic Potential of Matrix Metalloproteinases
Authors: Ashja Ardalan Arghavan , Khalili-Tanha Ghazaleh , Shoari Alireza
Published: November 2024

Lung cancer is a leading cause of cancer-related mortality worldwide, characterized by its aggressive nature and poor prognosis. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a pivotal role in the progression of lung cancer. They contribute to tumor invasion, metastasis, angiogenesis, and the modulation of the tumor microenvironment by degrading extracellular matrix components and regulating various cellular signaling pathways. Elevated levels of specific MMPs, such as MMP-2, MMP-9, and MMP-14, have been associated with advanced disease stages and reduced survival rates. As such, MMPs have emerged as valuable biomarkers for the diagnosis, prognosis, and prediction of treatment responses in lung cancer. This review aims to provide a comprehensive overview of the current understanding of MMPs in lung cancer, highlighting their diagnostic and prognostic significance, as well as their potential as therapeutic targets. Despite the initial setbacks in developing broad-spectrum MMP inhibitors, recent advancements have spurred interest in more selective inhibitors that minimize off-target effects and enhance therapeutic efficacy. Furthermore, combining MMP-targeted therapies with conventional treatments, such as chemotherapy and immunotherapy, holds promise for improving clinical outcomes. Future research directions include exploring novel MMP inhibitors, understanding the regulatory mechanisms of MMP activity, and integrating MMP biomarkers into personalized medicine approaches. As the field progresses, targeting MMPs may offer new therapeutic avenues and improve the prognosis for lung cancer patients, making this a promising area of investigation.
Reconstructing Intersection Conflict Zones: Microsimulation-Based Analysis of Traffic Safety for Pedestrians
Authors: Ištoka Otković Irena , Deluka-Tibljaš Aleksandra , Zečević Đuro , Šimunović Mirjana
Published: November 2024

According to statistics from the World Health Organization, traffic accidents are one of the leading causes of death among children and young people, and statistical indicators are even worse for the elderly population. Preventive measures require an approach that includes analyses of traffic infrastructure and regulations, users’ traffic behavior, and their interactions. In this study, a methodology based on traffic microsimulations was developed to select the optimal reconstruction solution for urban traffic infrastructure from the perspective of traffic safety. Comprehensive analyses of local traffic conditions at the selected location, infrastructural properties, and properties related to traffic users were carried out. The developed methodology was applied and tested at a selected unsignalized pedestrian crosswalk located in Osijek, Croatia, where traffic safety issues had been detected. Analyses of the possible solutions for traffic safety improvements were carried out, taking into account the specificities of the chosen location and the traffic participants’ behaviors, which were recorded and measured. The statistical analysis showed that children had shorter reaction times and crossed the street faster than the analyzed group of adult pedestrians, which was dominated by elderly people in this case. Using microsimulation traffic modeling (VISSIM), an analysis was conducted on the incoming vehicle speeds for both the existing and the reconstructed conflict zone solutions under different traffic conditions. The results exhibited a decrease in average speeds for the proposed solution, and traffic volume was detected to have a great impact on incoming speeds. The developed methodology proved to be effective in selecting a traffic solution that respects the needs of both motorized traffic and pedestrians.
Exploring the Potential of Robocasting for High-Density Electrolytes in Solid Oxide Fuel Cells
Authors: Licu Lidia , Matei Alexandru-Cristian , Caramarin Ștefania , Ioniță Florentina-Gabriela , Drăguț Dumitru-Valentin , Okos Alexandru , Ciobota Dan-Năstase
Published: November 2024

This study investigates the application of robocasting technology for fabricating high-density yttria-stabilized zirconia (8YSZ) electrolytes used in solid oxide fuel cells (SOFCs). The primary goal is to overcome the limitations of traditional manufacturing techniques, such as low density and poor microstructural control. Using a combination of hydrothermal synthesis, rheological testing, and robocasting, we achieved dense 8YSZ structures (over 95% density) with minimal porosity. The fabricated electrolytes underwent sintering and debinding processes, with thermal treatment profiles optimized for structural integrity. A microstructural analysis through SEM and XRD confirmed the formation of stable crystalline phase. This research opens new avenues for the use of additive manufacturing in electrochemical applications, particularly for producing complex ceramic components with superior characteristics.
Prospective Study on Splinting for First Carpometacarpal Joint: A Comparison of Conventional and Three-Dimensional Printed Splint
Authors: Inaba Naoto , Iwamoto Takuji , Ishii Kazunori , Oki Satoshi , Suzuki Taku , Sato Kazuki , Nagura Takeo , Nakamura Masaya
Published: November 2024

Background: Patient compliance is a major concern of hand orthosis in first carpometacarpal osteoarthritis. To address this issue, we established a method for creating a custom-made three-dimensional printed splint based on computed tomography. This prospective study evaluates the usefulness of the three-dimensional printed splint compared with the conventional splint. Methods: A total of 12 hands in nine patients were included. The mean age of the patients was 69 years (range: 58–84). Conventional orthoses were made by prosthetists using molds. Three-dimensional printed orthoses (long and short types) were digitally designed from computed tomography data and created using Fused Deposition Modeling. Subjects were instructed to use three types of orthoses for 2 weeks each. They completed questionnaires that indicated pain, function, percentage of daytime spent using the orthosis, satisfaction score, and discomfort caused by wearing orthoses. Results: The pain on motion showed an improvement of approximately 20% for all orthoses. There was no significant difference in pain scale, function, percentages of daytime spent using each orthosis, and satisfaction score among the three types of orthoses. Discomfort caused by wearing orthosis was more frequent in conventional orthosis than in 3D-printed orthosis, and there was a significant difference between the conventional type and the long-type 3D-printed orthosis. Conclusions: This study suggests that 3D-printed splints provide comparable pain relief to conventional splints with reduced discomfort. However, limitations such as small sample size, short follow-up, and reliance on CT imaging highlight the need for further research.
Comparative Evaluation of Sodium Hypochlorite Gel Penetration Using Er,Cr:YSGG Laser and Passive Ultrasonic Activation After Apicoectomy: An In Vitro Study with Confocal Laser Scanning Microscopy
Authors: Di Franco Joseph , Elafifi Ebeid Haitham , Betancourt Pablo , Pallarés-Sabater Antonio , Casino Alegre Alberto
Published: November 2024

Background: Lasers from the erbium family have been investigated to activate irrigation with sodium hypochlorite (NaOCl), improving the disinfection depth of the dentinal tubules of the root canal walls during root canal treatment. However, the possibility of laser-activated irrigation (LAI) in retro-cavity preparation has not been investigated to the date. The aim of our experimental study is to evaluate the efficacy of NaOCl gel penetration inside the dentinal tubules when activated during retro-cavity preparation, comparing passive ultrasonic activation (PUI) and Er,Cr:YSGG LAI. Materials and Methods: Fifty extracted mature single-root human teeth were divided into four groups (control, PUI, and two LAI groups with different NaOCl concentrations). After conventional endodontic treatment and root end resection, NaOCl gel (impregnated with rhodamine dye for confocal laser scanning microscopy (CLSM) analysis) was applied and activated according to the study group. The penetration index and mean penetration length were measured using computer software. Results: Both penetration index and mean penetration length were found to have increased in the PUI group compared to the control samples. However, LAI had a better penetration that was statistically significant compared to both the PUI and control groups. The difference in NaOCl concentration in the laser groups did not affect the penetration values. Conclusions: Within the limitations of our in vitro study using NaOCl gel activation in the retro-cavity after apicectomy, Er,Cr:YSGG LAI significantly enhanced NaOCl gel penetration capacity compared to PUI, regardless of its concentration. LAI can enhance its penetration in a safe way, avoiding its extrusion to the surrounding periapical tissues.
Salivary Nitrate Level and Lipid Profile in Patients with Hypertension: A Cross-Sectional Study in a Saudi Sub-Population
Authors: Assiri Khalil Ibrahim , Alqahtani Ali Mosfer A. , Alqarni Abdullah , Assiri Hassan Ahmed , Alassiri Saeed , Shaik Samiunnisa Begum , Dawasaz Ali Azhar , Hameed Mohammad Shahul
Published: November 2024

Background: The use of salivary biomarkers offers a non-invasive approach to understanding the metabolic and inflammatory status of hypertensive patients. This study aimed to quantify the salivary nitric oxide (NO), total cholesterol, triglycerides, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) levels in hypertensive individuals and healthy controls in a sub-population in Saudi Arabia. Methods: This cross-sectional study comprised 40 hypertensive patients (test group, 40–50 years old) and 40 age-matched healthy controls who visited the dental hospital in the College of Dentistry, King Khalid University, for dental treatment. Nitric oxide, total cholesterol, triglycerides, HDL, and LDL levels in saliva were assessed. An independent sample t-test was used to compare the results between the hypertensive and control groups. Results: The mean triglyceride and cholesterol levels in the test group were significantly higher (p < 0.05) than those in the control group. Alternatively, the NO level in the test group was significantly (p = 0.014) lower than that in the controls. The triglyceride level was significantly correlated with age in the test group (p = 0.04). Conclusions: This study demonstrated significant differences in the nitrate levels and lipid profiles between hypertensive patients and healthy individuals in a sub-population in Saudi Arabia. The findings indicate that saliva can be used as a non-invasive diagnostic tool for assessing nitrate levels and the lipid profile. However, additional studies with larger sample sizes and more precise testing parameters are required to validate the findings.
Hypotension with and Without Hypertensive Episodes During Endoscopic Adrenalectomy for Pheochromocytoma or Paraganglioma—Should Perioperative Treatment Be Individualized?
Authors: Tiboldi Akos , Gernhold Jonas , Scheuba Christian , Riss Philipp , Raber Wolfgang , Kabon Barbara , Niederle Bruno , Niederle Martin B.
Published: November 2024

Background: Hemodynamic instability is common during adrenalectomy for pheochromocytoma and paraganglioma (PPGL). Most analyses focus on the risk factors for intraoperative hypertension, but hypotension is a frequent and undesirable phenomenon during PPGL surgery. This study aimed to analyze the risk factors for hypotensive episodes during the removal of PPGL, and whether these episodes are always associated with concomitant intraoperative hypertensive events. Methods: A consecutive series of 121 patients (91.7% receiving preoperative alpha-blockade) treated with transperitoneal endoscopic adrenalectomy at a university hospital were analyzed, and pre- and intraoperative risk factors for intraoperative hypotension with or without intraoperative hypertension were analyzed using univariable and multivariable logistic regression analyses. Results: In total, 58 (56.2%) patients presented with intraoperative hypotension. Of these, 25 (20.7%) patients showed only hypotensive episodes but no hypertensive episodes (group 1), and 43 (35.5%) patients had both intraoperative hypotension and hypertension (group 2). The remaining 53 patients did not present with hypotension at all (group 3). When comparing group 1 (hypotension only) to all other patients with incidental diagnosis, higher age and lower preoperative diastolic arterial blood pressure (ABP) were significant risk factors for intraoperative hypotension; only the latter two were still significant in multivariate analysis. The significant risk factors for hypotension independent of hypertension (group 1 + 2 vs. group 3) were age and incidental diagnosis, pre-existing diabetes mellitus, and intraoperative use of remifentanil. Incidental diagnosis and use of remifentanil reached the level of significance in multivariate analysis. Conclusions: Since older age, incidental diagnosis of PPGL, lower preoperative ABP, and diabetes mellitus are risk factors for intraoperative hypotension, preoperative alpha-blocker treatment should be individualized for those at risk for hypotension. In addition, remifentanil should be used cautiously in the risk group.
Sensitive LC-MS/MS Assay for Total Testosterone Quantification on Unit Resolution and High-Resolution Instruments
Authors: Wolken Jill K. , Peterson Meghan M. , Cao Wenjing , Challoner Keith , Jin Zhicheng
Published: November 2024

Background: Testosterone is an androgenic hormone that plays important roles in both males and females. The circulating levels of total testosterone vary from 1 to 1480 ng/dL. High-throughput immunoassays often lack accuracy in lower concentration ranges (below 100 ng/dL), particularly when used for females or children. To address this limitation, we developed a total testosterone LC-MS/MS assay on three instruments. Methods: Sample preparation began with the dilution and conditioning of 200 µL of serum. A supported liquid extraction cartridge was used to extract the analyte from biological matrices. Chromatographic separation was achieved using a C18 column with a runtime of 5 min per sample. This assay was validated on a Triple Quad 6500 and an API 4500 instrument. Results: Method validation was carried out according to the CLSI C62-ED2 guideline and our hospital protocol. The within-day coefficient of variation (CV) was less than 10% and the between-day CV was less than 15%. The assay had a limit of quantitation of 0.5 ng/dL with an analyte measure range of 2–1200 ng/dL. A comparison using Deming regression and Bland–Altman plots showed that this assay correlated well with a reference method. The results from the API 4500 and an Orbitrap were consistent with those from the TQ 6500. Both serum-separator tubes (BD) and serum-activator tubes were found to be suitable. Conclusions: We successfully developed and validated a robust total testosterone LC-MS/MS assay for routine clinical testing. This assay was harmonized across two triple quadrupole instruments and one high-resolution mass spectrometer.