bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription Factor SmSPL2 Inhibits the Accumulation of Salvianolic Acid B and Influences Root Architecture
Authors: Wang Xiangzeng , Cao Yao , Yang Jiaxin , Zhang Tong , Yang Qianqian , Zhang Yanhua , Wang Donghao , Cao Xiaoyan
Published: November 2022

The SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) transcription factor play vital roles in plant growth and development. Although 15 SPL family genes have been recognized in the model medical plant Salvia miltiorrhiza Bunge, most of them have not been functionally characterized to date. Here, we performed a careful characterization of SmSPL2, which was expressed in almost all tissues of S. miltiorrhiza and had the highest transcriptional level in the calyx. Meanwhile, SmSPL2 has strong transcriptional activation activity and resides in the nucleus. We obtained overexpression lines of SmSPL2 and rSmSPL2 (miR156-resistant SmSPL2). Morphological changes in roots, including longer length, fewer adventitious roots, decreased lateral root density, and increased fresh weight, were observed in all of these transgenic lines. Two rSmSPL2-overexpressed lines were subjected to transcriptome analysis. Overexpression of rSmSPL2 changed root architectures by inhibiting biosynthesis and signal transduction of auxin, while triggering that of cytokinin. The salvianolic acid B (SalB) concentration was significantly decreased in rSmSPL2-overexpressed lines. Further analysis revealed that SmSPL2 binds directly to the promoters of Sm4CL9, SmTAT1, and SmPAL1 and inhibits their expression. In conclusion, SmSPL2 is a potential gene that efficiently manipulate both root architecture and SalB concentration in S. miltiorrhiza.
WideEffHunter: An Algorithm to Predict Canonical and Non-Canonical Effectors in Fungi and Oomycetes
Authors: Carreón-Anguiano Karla Gisel , Todd Jewel Nicole Anna , Chi-Manzanero Bartolomé Humberto , Couoh-Dzul Osvaldo Jhosimar , Islas-Flores Ignacio , Canto-Canché Blondy
Published: November 2022

Newer effectorome prediction algorithms are considering effectors that may not comply with the canonical characteristics of small, secreted, cysteine-rich proteins. The use of effector-related motifs and domains is an emerging strategy for effector identification, but its use has been limited to individual species, whether oomycete or fungal, and certain domains and motifs have only been associated with one or the other. The use of these strategies is important for the identification of novel, non-canonical effectors (NCEs) which we have found to constitute approximately 90% of the effectoromes. We produced an algorithm in Bash called WideEffHunter that is founded on integrating three key characteristics: the presence of effector motifs, effector domains and homology to validated existing effectors. Interestingly, we found similar numbers of effectors with motifs and domains within two different taxonomic kingdoms: fungi and oomycetes, indicating that with respect to their effector content, the two organisms may be more similar than previously believed. WideEffHunter can identify the entire effectorome (non-canonical and canonical effectors) of oomycetes and fungi whether pathogenic or non-pathogenic, unifying effector prediction in these two kingdoms as well as the two different lifestyles. The elucidation of complete effectoromes is a crucial step towards advancing effectoromics and disease management in agriculture.
Hematopoietic and Chronic Myeloid Leukemia Stem Cells: Multi-Stability versus Lineage Restriction
Authors: Brown Geoffrey
Published: November 2022

There is compelling evidence to support the view that the cell-of-origin for chronic myeloid leukemia is a hematopoietic stem cell. Unlike normal hematopoietic stem cells, the progeny of the leukemia stem cells are predominantly neutrophils during the disease chronic phase and there is a mild anemia. The hallmark oncogene for chronic myeloid leukemia is the BCR-ABLp210 fusion gene. Various studies have excluded a role for BCR-ABLp210 expression in maintaining the population of leukemia stem cells. Studies of BCR-ABLp210 expression in embryonal stem cells that were differentiated into hematopoietic stem cells and of the expression in transgenic mice have revealed that BCR-ABLp210 is able to veer hematopoietic stem and progenitor cells towards a myeloid fate. For the transgenic mice, global changes to the epigenetic landscape were observed. In chronic myeloid leukemia, the ability of the leukemia stem cells to choose from the many fates that are available to normal hematopoietic stem cells appears to be deregulated by BCR-ABLp210 and changes to the epigenome are also important. Even so, we still do not have a precise picture as to why neutrophils are abundantly produced in chronic myeloid leukemia.
The Effect of Femtosecond Laser Irradiation and Plasmon Field on the Degree of Conversion of a UDMA-TEGDMA Copolymer Nanocomposite Doped with Gold Nanorods
Authors: Bonyár Attila , Szalóki Melinda , Borók Alexandra , Rigó István , Kámán Judit , Zangana Shereen , Veres Miklós , Rácz Péter , Aladi Márk , Kedves Miklós , Szokol Ágnes , Petrik Péter , Fogarassy Zsolt , Molnár Kolos , Csete Mária , Szenes András , Tóth Emese , Vas Dávid , Papp István , Galbács Gábor , Csernai László , Biró Tamás , Kroó Norbert ,   Collaboration
Published: November 2022

In this work, the effects of femtosecond laser irradiation and doping with plasmonic gold nanorods on the degree of conversion (DC) of a urethane dimethacrylate (UDMA)–triethylene glycol dimethacrylate (TEGDMA) nanocomposite were investigated. The UDMA-TEGDMA photopolymer was prepared in a 3:1 weight ratio and doped with dodecanethiol- (DDT) capped gold nanorods of 25 × 75 or 25 × 85 nm nominal diameter and length. It was found that the presence of the gold nanorods alone (without direct plasmonic excitation) can increase the DC of the photopolymer by 6–15%. This increase was found to be similar to what could be achieved with a control heat treatment of 30 min at 180 °C. It was also shown that femtosecond laser impulses (795 nm, 5 mJ pulse energy, 50 fs pulse length, 2.83 Jcm−2 fluence), applied after the photopolymerization under a standard dental curing lamp, can cause a 2–7% increase in the DC of undoped samples, even after thermal pre-treatment. The best DC values (12–15% increase) were obtained with combined nanorod doping and subsequent laser irradiation close to the plasmon resonance peak of the nanorods (760–800 nm), which proves that the excited plasmon field can directly facilitate double bond breakage (without thermoplasmonic effects due to the short pulse length) and increase the crosslink density independently from the initial photopolymerization process.
SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways
Authors: Lee Jina , Kim Jinju , Lee Jae-Hyung , Choi Yong Min , Choi Hyeonil , Cho Hwan-Doo , Cha Guang-Ho , Lee Young-Ha , Jo Eun-Kyeong , Park Byung-Hyun , Yuk Jae-Min
Published: November 2022

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1−/− mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.
Transcriptome Profiling of the Resistance Response of Musa acuminata subsp. burmannicoides, var. Calcutta 4 to Pseudocercospora musae
Authors: Pinheiro Tatiana David Miranda , Rego Erica Cristina Silva , Alves Gabriel Sergio Costa , Fonseca Fernando Campos De Assis , Cotta Michelle Guitton , Antonino Jose Dijair , Gomes Taísa Godoy , Amorim Edson Perito , Ferreira Claudia Fortes , Costa Marcos Mota Do Carmo , Grynberg Priscila , Togawa Roberto Coiti , Miller Robert Neil Gerard
Published: November 2022

Banana (Musa spp.), which is one of the world’s most popular and most traded fruits, is highly susceptible to pests and diseases. Pseudocercospora musae, responsible for Sigatoka leaf spot disease, is a principal fungal pathogen of Musa spp., resulting in serious economic damage to cultivars in the Cavendish subgroup. The aim of this study was to characterize genetic components of the early immune response to P. musae in Musa acuminata subsp. burmannicoides, var. Calcutta 4, a resistant wild diploid. Leaf RNA samples were extracted from Calcutta 4 three days after inoculation with fungal conidiospores, with paired-end sequencing conducted in inoculated and non-inoculated controls using lllumina HiSeq 4000 technology. Following mapping to the reference M. acuminata ssp. malaccensis var. Pahang genome, differentially expressed genes (DEGs) were identified and expression representation analyzed on the basis of gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes orthology and MapMan pathway analysis. Sequence data mapped to 29,757 gene transcript models in the reference Musa genome. A total of 1073 DEGs were identified in pathogen-inoculated cDNA libraries, in comparison to non-inoculated controls, with 32% overexpressed. GO enrichment analysis revealed common assignment to terms that included chitin binding, chitinase activity, pattern binding, oxidoreductase activity and transcription factor (TF) activity. Allocation to KEGG pathways revealed DEGs associated with environmental information processing, signaling, biosynthesis of secondary metabolites, and metabolism of terpenoids and polyketides. With 144 up-regulated DEGs potentially involved in biotic stress response pathways, including genes involved in cell wall reinforcement, PTI responses, TF regulation, phytohormone signaling and secondary metabolism, data demonstrated diverse early-stage defense responses to P. musae. With increased understanding of the defense responses occurring during the incompatible interaction in resistant Calcutta 4, these data are appropriate for the development of effective disease management approaches based on genetic improvement through introgression of candidate genes in superior cultivars.
The Cognitive Improvement and Alleviation of Brain Hypermetabolism Caused by FFAR3 Ablation in Tg2576 Mice Is Persistent under Diet-Induced Obesity
Authors: Solas Maite , Zamarbide Marta , Ardanaz Carlos G. , Ramírez María J. , Pérez-Mediavilla Alberto
Published: November 2022

Obesity and aging are becoming increasingly prevalent across the globe. It has been established that aging is the major risk factor for Alzheimer’s disease (AD), and it is becoming increasingly evident that obesity and the associated insulin resistance are also notably relevant risk factors. The biological plausibility of the link between high adiposity, insulin resistance, and dementia is central for understanding AD etiology, and to form bases for prevention efforts to decrease the disease burden. Several studies have demonstrated a strong association between short chain fatty acid receptor FFAR3 and insulin sensitivity. Interestingly, it has been recently established that FFAR3 mRNA levels are increased in early stages of the AD pathology, indicating that FFAR3 could play a key role in AD onset and progression. Indeed, in the present study we demonstrate that the ablation of the Ffar3 gene in Tg2576 mice prevents the development of cognitive deficiencies in advanced stages of the disease. Notably, this cognitive improvement is also maintained upon a severe metabolic challenge such as the exposure to high-fat diet (HFD) feeding. Moreover, FFAR3 deletion restores the brain hypermetabolism displayed by Tg2576 mice. Collectively, these data postulate FFAR3 as a potential novel target for AD.
Biochemical Characterization of Pyranose Oxidase from Streptomyces canus—Towards a Better Understanding of Pyranose Oxidase Homologues in Bacteria
Authors: Kostelac Anja , Sützl Leander , Puc Jolanta , Furlanetto Valentina , Divne Christina , Haltrich Dietmar
Published: November 2022

Pyranose oxidase (POx, glucose 2-oxidase; EC 1.1.3.10, pyranose:oxygen 2-oxidoreductase) is an FAD-dependent oxidoreductase and a member of the auxiliary activity (AA) enzymes (subfamily AA3_4) in the CAZy database. Despite the general interest in fungal POxs, only a few bacterial POxs have been studied so far. Here, we report the biochemical characterization of a POx from Streptomyces canus (ScPOx), the sequence of which is positioned in a separate, hitherto unexplored clade of the POx phylogenetic tree. Kinetic analyses revealed that ScPOx uses monosaccharide sugars (such as d-glucose, d-xylose, d-galactose) as its electron-donor substrates, albeit with low catalytic efficiencies. Interestingly, various C- and O-glycosides (such as puerarin) were oxidized by ScPOx as well. Some of these glycosides are characteristic substrates for the recently described FAD-dependent C-glycoside 3-oxidase from Microbacterium trichothecenolyticum. Here, we show that FAD-dependent C-glycoside 3-oxidases and pyranose oxidases are enzymes belonging to the same sequence space.
Human Mesenchymal Stem Cell Secretome Driven T Cell Immunomodulation Is IL-10 Dependent
Authors: Shephard Matthew T. , Merkhan Marwan M. , Forsyth Nicholas R.
Published: November 2022

The Human Mesenchymal Stem Cell (hMSC) secretome has pleiotropic effects underpinning its therapeutic potential. hMSC serum-free conditioned media (SFCM) contains a variety of cytokines, with previous studies linking a changed secretome composition to physoxia. The Jurkat T cell model allowed the efficacy of SFCM vs. serum-free media (SFM) in the suppression of immunological aspects, including proliferation and polarisation, to be explored. Cell growth in SFM was higher [(21% O2 = 5.3 × 105 ± 1.8 × 104 cells/mL) and (2% O2 = 5.1 × 105 ± 3.0 × 104 cells/mL)], compared to SFCM [(21% O2 = 2.4 × 105 ± 2.5 × 104 cells/mL) and (2% O2 = 2.2 × 105 ± 5.8 × 103 cells/mL)]. SFM supported IL-2 release following activation [(21% O2 = 5305 ± 211 pg/mL) and (2% O2 = 5347 ± 327 pg/mL)] whereas SFCM suppressed IL-2 secretion [(21% O2 = 2461 ± 178 pg/mL) and (2% O2 = 1625 ± 159 pg/mL)]. Anti-inflammatory cytokines, namely IL-4, IL-10, and IL-13, which we previously confirmed as components of hMSC SFCM, were tested. IL-10 neutralisation in SFCM restored proliferation in both oxygen environments (SFM/SFCM+antiIL−10 ~1-fold increase). Conversely, IL-4/IL-13 neutralisation showed no proliferation restoration [(SFM/SFM+antiIL−4 ~2-fold decrease), and (SFM/SFCM+antiIL−13 ~2-fold decrease)]. Present findings indicate IL-10 played an immunosuppressive role by reducing IL-2 secretion. Identification of immunosuppressive components of the hMSC secretome and a mechanistic understanding of their action allow for the advancement and refinement of potential future cell-free therapies.
The High Plasticity of Nonpathogenic Mycobacterium brumae Induces Rapid Changes in Its Lipid Profile during Pellicle Maturation: The Potential of This Bacterium as a Versatile Cell Factory for Lipid Compounds of Therapeutic Interest
Authors: Campo-Pérez Víctor , Guallar-Garrido Sandra , Luquin Marina , Sánchez-Chardi Alejandro , Julián Esther
Published: November 2022

The immunomodulatory potential of mycobacteria to be used for therapeutic purposes varies by species and culture conditions and is closely related to mycobacterial lipid composition. Although the lipids present in the mycobacterial cell wall are relevant, lipids are mainly stored in intracellular lipid inclusions (ILIs), which have emerged as a crucial structure in understanding mycobacteria-host interaction. Little is known about ILI ultrastructure, production, and composition in nonpathogenic species. In this study, we compared the lipid profiles of the nonpathogenic immunomodulatory agent Mycobacterium brumae during pellicle maturation under different culture conditions with qualitative and quantitative approaches by using high-resolution imaging and biochemical and composition analyses to understand ILI dynamics. The results showed wax esters, mainly in early stages of development, and acylglycerols in mature ILI composition, revealing changes in dynamics, amount, and morphometry, depending on pellicle maturation and the culture media used. Low-glycerol cultures induced ILIs with lower molecular weights which were smaller in size in comparison with the ILIs produced in glycerol-enriched media. The data also indicate the simple metabolic plasticity of lipid synthesis in M. brumae, as well as its high versatility in generating different lipid profiles. These findings provide an interesting way to enhance the production of key lipid structures via the simple modulation of cell culture conditions.
Time-Resolved Proteomics of Germinating Spores of Bacillus cereus
Authors: Gao Xiaowei , Swarge Bhagyashree N. , Roseboom Winfried , Setlow Peter , Brul Stanley , Kramer Gertjan
Published: November 2022

Bacillus cereus is a spore-forming human pathogen that is a burden to the food chain. Dormant spores are highly resistant to harsh environmental conditions, but lose resistance after germination. In this study, we investigate the B. cereus spore proteome upon spore germination and outgrowth so as to obtain new insights into the molecular mechanisms involved. We used mass spectrometry combined with co-expression network analysis and obtained a unique global proteome view of the germination and outgrowth processes of B. cereus spores by monitoring 2211 protein changeovers. We are the first to examine germination and outgrowth models of B. cereus spores experimentally by studying the dynamics of germinant receptors, other proteins involved in spore germination and resistance, and coat and exosporium proteins. Furthermore, through the co-expression analysis of 1175 proteins identified with high quality data, germination proteome data were clustered into eight modules (termed black, blue, brown, green, red, turquoise, grey, and yellow), whose associated functions and expression profiles were investigated. Germination related proteins were clustered into blue and brown modules, the abundances of which decreased after finishing germination. In the brown and blue we identified 124 proteins that could be vital during germination. These proteins will be very interesting to study in future genetic studies regarding their function in spore revival in B. cereus.
On the Bioactivity of Echinacea purpurea Extracts to Modulate the Production of Inflammatory Mediators
Authors: Vieira Sara F. , Gonçalves Virgínia M. F. , Llaguno Carmen P. , Macías Felipe , Tiritan Maria Elizabeth , Reis Rui L. , Ferreira Helena , Neves Nuno M.
Published: November 2022

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography–high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1β, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.
Genome-Wide Association Study Reveals Novel QTLs and Candidate Genes for Grain Number in Rice
Authors: Li Peiyuan , Li Qing , Lu Xueli , Dai Liping , Yang Long , Hong Yifeng , Yan Tiancai , Shen Lan , Zhang Qiang , Ren Deyong , Zhu Li , Hu Jiang , Dong Guojun , Zhang Guangheng , Qian Qian , Zeng Dali
Published: November 2022

Grain number per panicle (GNPP), determined mainly by panicle branching, is vital for rice yield. The dissection of the genetic basis underlying GNPP could help to improve rice yield. However, genetic resources, including quantitative trait loci (QTL) or genes for breeders to enhance rice GNPP, are still limited. Here, we conducted the genome-wide association study (GWAS) on the GNPP, primary branch number (PBN), and secondary branch number (SBN) of 468 rice accessions. We detected a total of 18 QTLs, including six for GNPP, six for PBN, and six for SBN, in the whole panel and the indica and japonica subpanels of 468 accessions. More importantly, qPSG1 was a common QTL for GNPP, PBN, and SBN and was demonstrated by chromosome segment substitution lines (CSSLs). Considering gene annotation, expression, and haplotype analysis, seven novel and strong GNPP-related candidate genes were mined from qPSG1. Our results provide clues to elucidate the molecular regulatory network of GNPP. The identified QTLs and candidate genes will contribute to the improvement of GNPP and rice yield via molecular marker-assisted selection (MAS) breeding and genetic engineering techniques.
Latifolin, a Natural Flavonoid, Isolated from the Heartwood of Dalbergia odorifera Induces Bioactivities through Apoptosis, Autophagy, and Necroptosis in Human Oral Squamous Cell Carcinoma
Authors: Yun Hyung-Mun , Park Ji Eun , Lee Joon Yeop , Park Kyung-Ran
Published: November 2022

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm with frequent metastasis and high mortality in the oral cavity. Plant-derived natural compounds are actively progressing as a trend for cancer treatment. Latifolin (Latif), is a natural flavonoid isolated from the heartwood of Dalbergia odorifera T. Chen (D. odorifera) has been known to have beneficial effects on anti-aging, anti-carcinogenic, anti-inflammatory, and cardio-protective activities. However, the anti-cancer effects of Latif are unknown in OSCC. Herein, as a result of analysis in terms of the aggressive features of OSCCs, we found that Latif significantly inhibited the cell proliferation of human YD-8 and YD-10B OSCCs, and caused the anti-metastatic activities by effectively blocking cell migration, invasion, and adhesion via the inactivation of focal adhesion kinase (FAK)/non-receptor tyrosine kinase (Src). Moreover, we found that Latif induced apoptotic cell death to suppress the cell survival and proliferation of YD-10B OSCCs by targeting PI3K/AKT/mTOR/p70S6K signaling. Finally, we analyzed in terms of autophagy and necroptosis, which are other mechanisms of programmed cell death and survival compared to apoptosis in YD-10B OSCCs. We found that Latif suppressed autophagic-related proteins and autophagosome formation, and also Latif inhibited necroptosis by dephosphorylating necroptosis-regulatory proteins (RIP1, RIP3, and MLKL). Given these findings, our results provided new evidence for Latif’s biological effect and mechanism in YD-10B OSCCs, suggesting that Latif may be a new candidate for patients with OSCCs.
Exploring the RNA Editing Events and Their Potential Regulatory Roles in Tea Plant (Camellia sinensis L.)
Authors: Zhang Mengyuan , Li Zhuo , Wang Zijian , Xiao Yao , Bao Lu , Wang Min , An Chuanjing , Gao Yuefang
Published: November 2022

RNA editing is a post-transcriptional modification process that alters the RNA sequence relative to the genomic blueprint. In plant organelles (namely, mitochondria and chloroplasts), the most common type is C-to-U, and the absence of C-to-U RNA editing results in abnormal plant development, such as etiolation and albino leaves, aborted embryonic development and retarded seedling growth. Here, through PREP, RES-Scanner, PCR and RT-PCR analyses, 38 and 139 RNA editing sites were identified from the chloroplast and mitochondrial genomes of Camellia sinensis, respectively. Analysis of the base preference around the RNA editing sites showed that in the −1 position of the edited C had more frequent occurrences of T whereas rare occurrences of G. Three conserved motifs were identified at 25 bases upstream of the RNA editing site. Structural analyses indicated that the RNA secondary structure of 32 genes, protein secondary structure of 37 genes and the three-dimensional structure of 5 proteins were altered due to RNA editing. The editing level analysis of matK and ndhD in six tea cultivars indicated that matK-701 might be involved in the color change of tea leaves. Furthermore, 218 PLS-CsPPR proteins were predicted to interact with the identified RNA editing sites. In conclusion, this study provides comprehensive insight into RNA editing events, which will facilitate further study of the RNA editing phenomenon of the tea plant.
The Cysteine Protease Giardipain-1 from Giardia duodenalis Contributes to a Disruption of Intestinal Homeostasis
Authors: Quezada-Lázaro Rodrigo , Vázquez-Cobix Yessica , Fonseca-Liñán Rocío , Nava Porfirio , Hernández-Cueto Daniel Dimitri , Cedillo-Peláez Carlos , López-Vidal Yolanda , Huerta-Yepez Sara , Ortega-Pierres M. Guadalupe
Published: November 2022

In giardiasis, diarrhoea, dehydration, malabsorption, weight loss and/or chronic inflammation are indicative of epithelial barrier dysfunction. However, the pathogenesis of giardiasis is still enigmatic in many aspects. Here, we show evidence that a cysteine protease of Giardia duodenalis called giardipain-1, contributes to the pathogenesis of giardiasis induced by trophozoites of the WB strain. In an experimental system, we demonstrate that purified giardipain-1 induces apoptosis and extrusion of epithelial cells at the tips of the villi in infected jirds (Meriones unguiculatus). Moreover, jird infection with trophozoites expressing giardipain-1 resulted in intestinal epithelial damage, cellular infiltration, crypt hyperplasia, goblet cell hypertrophy and oedema. Pathological alterations were more pronounced when jirds were infected intragastrically with Giardia trophozoites that stably overexpress giardipain-1. Furthermore, Giardia colonization in jirds results in a chronic inflammation that could relate to the dysbiosis triggered by the protist. Taken together, these results reveal that giardipain-1 plays a key role in the pathogenesis of giardiasis.
Modulation of the Functional State of Mouse Neutrophils by Selenium Nanoparticles In Vivo
Authors: Mal’tseva Valentina N. , Gudkov Sergey V. , Turovsky Egor A.
Published: November 2022

This study aimed to discover the immunomodulatory effect of selenium nanoparticles (SeNPs) on the functional state of neutrophils in vivo. Intraperitoneal injections of SeNPs (size 100 nm) 2.5 mg/kg/daily to BALB/c mice for a duration of 7–28 days led to the development of an inflammatory reaction, which was registered by a significant increase in the number of neutrophils released from the peritoneal cavity, as well as their activated state, without additional effects. At the same time, subcutaneous injections of the same SeNPs preparations at concentrations of 0.1, 0.5, and 2.5 mg/kg, on the contrary, modulated the functional state of neutrophils depending on the concentration and duration of SeNPs administration. With the use of fluorescence spectroscopy, chemiluminescence, biochemical methods, and PCR analysis, it was found that subcutaneous administration of SeNPs (0.1, 0.5, and 2.5 mg/kg) to mice for a short period of time (7–14 days) leads to modification of important neutrophil functions (adhesion, the number of migrating cells into the peritoneal cell cavity, ROS production, and NET formation). The obtained results indicated the immunostimulatory and antioxidant effects of SeNPs in vivo during short-term administration, while the most pronounced immunomodulatory effects of SeNPs were observed with the introduction of a low concentration of SeNPs (0.1 mg/kg). Increase in the administration time of SeNPs (0.1 mg/kg or 2.5 mg/kg) up to 28 days led to a decrease in the adhesive abilities of neutrophils and suppression of the expression of mRNA of adhesive molecules, as well as proteins involved in the generation of ROS, with the exception of NOX2; there was a tendency to suppress gene expression pro-inflammatory factors, which indicates the possible manifestation of immunosuppressive and anti-inflammatory effects of SeNPs during their long-term administration. Changes in the expression of selenoproteins also had features depending on the concentration and duration of the administered SeNPs. Selenoprotein P, selenoprotein M, selenoprotein S, selenoprotein K, and selenoprotein T were the most sensitive to the introduction of SeNPs into the mouse organism, which indicates their participation in maintaining the functional status of neutrophils, and possibly mediated the immunomodulatory effect of SeNPs.
Emerging Effects of IL-33 on COVID-19
Authors: Gao Yuan , Cai Luwei , Li Lili , Zhang Yidan , Li Jing , Luo Chengliang , Wang Ying , Tao Luyang
Published: November 2022

Since the start of COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 6 million people have lost their lives worldwide directly or indirectly. Despite intensified efforts to clarify the immunopathology of COVID-19, the key factors and processes that trigger an inflammatory storm and lead to severe clinical outcomes in patients remain unclear. As an inflammatory storm factor, IL-33 is an alarmin cytokine, which plays an important role in cell damage or infection. Recent studies have shown that serum IL-33 is upregulated in COVID-19 patients and is strongly associated with poor outcomes. Increased IL-33 levels in severe infections may result from an inflammatory storm caused by strong interactions between activated immune cells. However, the effects of IL-33 in COVID-19 and the underlying mechanisms remain to be fully elucidated. In this review, we systematically discuss the biological properties of IL-33 under pathophysiological conditions and its regulation of immune cells, including neutrophils, innate lymphocytes (ILCs), dendritic cells, macrophages, CD4+ T cells, Th17/Treg cells, and CD8+ T cells, in COVID-19 phagocytosis. The aim of this review is to explore the potential value of the IL-33/immune cell pathway as a new target for early diagnosis, monitoring of severe cases, and clinical treatment of COVID-19.
RETRACTED: Impact of Histone Modifications and Their Therapeutic Targeting in Hematological Malignancies
Authors: Markouli Mariam , Strepkos Dimitrios , Piperi Christina
Published: November 2022

Hematologic malignancies are a large and heterogeneous group of neoplasms characterized by complex pathogenetic mechanisms. The abnormal regulation of epigenetic mechanisms and specifically, histone modifications, has been demonstrated to play a central role in hematological cancer pathogenesis and progression. A variety of epigenetic enzymes that affect the state of histones have been detected as deregulated, being either over- or underexpressed, which induces changes in chromatin compaction and, subsequently, affects gene expression. Recent advances in the field of epigenetics have revealed novel therapeutic targets, with many epigenetic drugs being investigated in clinical trials. The present review focuses on the biological impact of histone modifications in the pathogenesis of hematologic malignancies, describing a wide range of therapeutic agents that have been discovered to target these alterations and are currently under investigation in clinical trials.
Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors’ Combination
Authors: Quesada-Vázquez Sergio , Bone Caitlin , Saha Shikha , Triguero Iris , Colom-Pellicer Marina , Aragonès Gerard , Hildebrand Falk , del Bas Josep M. , Caimari Antoni , Beraza Naiara , Escoté Xavier
Published: November 2022

The gut is a selective barrier that not only allows the translocation of nutrients from food, but also microbe-derived metabolites to the systemic circulation that flows through the liver. Microbiota dysbiosis occurs when energy imbalances appear due to an unhealthy diet and a sedentary lifestyle. Dysbiosis has a critical impact on increasing intestinal permeability and epithelial barrier deterioration, contributing to bacterial and antigen translocation to the liver, triggering non-alcoholic fatty liver disease (NAFLD) progression. In this study, the potential therapeutic/beneficial effects of a combination of metabolic cofactors (a multi-ingredient; MI) (betaine, N-acetylcysteine, L-carnitine, and nicotinamide riboside) against NAFLD were evaluated. In addition, we investigated the effects of this metabolic cofactors’ combination as a modulator of other players of the gut-liver axis during the disease, including gut barrier dysfunction and microbiota dysbiosis. Diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (NAFLD group) or with a combination of metabolic cofactors (NAFLD-MI group), and small intestines were harvested from all animals for histological, molecular, and omics analysis. The MI treatment ameliorated gut morphological changes, decreased gut barrier permeability, and reduced gene expression of some proinflammatory cytokines. Moreover, epithelial cell proliferation and the number of goblet cells were increased after MI supplementation. In addition, supplementation with the MI combination promoted changes in the intestinal microbiota composition and diversity, as well as modulating short-chain fatty acids (SCFAs) concentrations in feces. Taken together, this specific combination of metabolic cofactors can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.
circSMARCA5 Is an Upstream Regulator of the Expression of miR-126-3p, miR-515-5p, and Their mRNA Targets, Insulin-like Growth Factor Binding Protein 2 (IGFBP2) and NRAS Proto-Oncogene, GTPase (NRAS) in Glioblastoma
Authors: Merulla Aurora Eliana , Stella Michele , Barbagallo Cristina , Battaglia Rosalia , Caponnetto Angela , Broggi Giuseppe , Altieri Roberto , Certo Francesco , Caltabiano Rosario , Ragusa Marco , Barbagallo Giuseppe Maria Vincenzo , Di Pietro Cinzia , Purrello Michele , Barbagallo Davide
Published: November 2022

The involvement of non-coding RNAs (ncRNAs) in glioblastoma multiforme (GBM) pathogenesis and progression has been ascertained but their cross-talk within GBM cells remains elusive. We previously demonstrated the role of circSMARCA5 as a tumor suppressor (TS) in GBM. In this paper, we explore the involvement of circSMARCA5 in the control of microRNA (miRNA) expression in GBM. By using TaqMan® low-density arrays, the expression of 748 miRNAs was assayed in U87MG overexpressing circSMARCA5. Differentially expressed (DE) miRNAs were validated through single TaqMan® assays in: (i) U87MG overexpressing circSMARCA5; (ii) four additional GBM cell lines (A172; CAS-1; SNB-19; U251MG); (iii) thirty-eight GBM biopsies; (iv) twenty biopsies of unaffected brain parenchyma (UC). Validated targets of DE miRNAs were selected from the databases TarBase and miRTarbase, and the literature; their expression was inferred from the GBM TCGA dataset. Expression was assayed in U87MG overexpressing circSMARCA5, GBM cell lines, and biopsies through real-time PCR. TS miRNAs 126-3p and 515-5p were upregulated following circSMARCA5 overexpression in U87MG and their expression was positively correlated with that of circSMARCA5 (r-values = 0.49 and 0.50, p-values = 9 × 10−5 and 7 × 10−5, respectively) in GBM biopsies. Among targets, IGFBP2 (target of miR-126-3p) and NRAS (target of miR-515-5p) mRNAs were positively correlated (r-value = 0.46, p-value = 0.00027), while their expression was negatively correlated with that of circSMARCA5 (r-values = −0.58 and −0.30, p-values = 0 and 0.019, respectively), miR-126-3p (r-value = −0.36, p-value = 0.0066), and miR-515-5p (r-value = −0.34, p-value = 0.010), respectively. Our data identified a new GBM subnetwork controlled by circSMARCA5, which regulates downstream miRNAs 126-3p and 515-5p, and their mRNA targets IGFBP2 and NRAS.
Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients—A Proof of Concept
Authors: Bergantim Rui , Peixoto da Silva Sara , Polónia Bárbara , Barbosa Mélanie A. G. , Albergaria André , Lima Jorge , Caires Hugo R. , Guimarães José E. , Vasconcelos M. Helena
Published: November 2022

Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD.
Understanding the Role of Yeast Yme1 in Mitochondrial Function Using Biochemical and Proteomics Analyses
Authors: Kan Kwan Ting , Nelson Michael G. , Grant Chris M. , Hubbard Simon J. , Lu Hui
Published: November 2022

Mitochondrial i-AAA proteinase Yme1 is a multifunctional protein that plays important roles in maintaining mitochondrial protein homeostasis and regulating biogenesis and function of mitochondrial proteins. However, due to the complex interplay of mitochondria and the multifunctional nature of Yme1, how Yme1 affects mitochondrial function and protein homeostasis is still poorly understood. In this study, we investigated how YME1 deletion affects yeast Saccharomyces cerevisiae growth, chronological life span, mitochondrial protein homeostasis and function, with a focus on the mitochondrial oxidative phosphorylation (OXPHOS) complexes. Our results show that whilst the YME1 deleted cells grow poorly under respiratory conditions, they grow similar to wild-type yeast under fermentative conditions. However, the chronological life span is impaired, indicating that Yme1 plays a key role in longevity. Using highly enriched mitochondrial extract and proteomic analysis, we show that the abundances of many mitochondrial proteins are altered by YME1 deletion. Several components of the respiratory chain complexes II, III, IV and V were significantly decreased, suggesting that Yme1 plays an important role in maintaining the level and function of complexes II-V. This result was confirmed using blue native-PAGE and in-solution-based enzyme activity assays. Taken together, this study shows that Yme1 plays an important role in the chronological life span and mitochondrial protein homeostasis and has deciphered its function in maintaining the activity of mitochondrial OXPHOS complexes.
Polydopamine Nanoparticles Functionalized Electrochemical DNA Aptasensor for Serum Glycated Albumin Detection
Authors: Maraming Pornsuda , Aye Nang Noon Shean , Boonsiri Patcharee , Daduang Sakda , Buhome Onanong , Daduang Jureerut
Published: November 2022

Polydopamine (PDA) has now been widely applied to electrochemical biosensing because of its excellent biocompatibility, abundant functional groups, and facile preparation. In this study, polydopamine nanoparticles (PDA-NPs)-functionalized electrochemical aptasensor was developed for the rapid, sensitive, and cost-effective detection of glycated albumin (GA), a promising biomarker for glycemic control in diabetic patients. PDA-NPs were synthesized at various pH conditions in Tris buffer. Cyclic voltammetry (CV) of PDA-NPs-coated screen-printed carbon electrodes (SPCEs) revealed that the materials were more conductive when PDA-NPs were synthesized at pH 9.5 and 10.5 than that at pH 8.5. At pH 10.5, the prepared PDA and PDA-aptamer NPs were monodispersed spherical morphology with an average size of 118.0 ± 1.9 and 127.8 ± 2.0 nm, respectively. When CV and electrochemical impedance spectrometry (EIS) were used for the characterization and detection of the electrochemical aptasensor under optimal conditions, the proposed aptasensor exhibited a broad linearity for detection of GA at a clinically relevant range of (1–10,000 µg mL−1), provided a low detection limit of 0.40 µg mL−1, appreciable reproducibility (less than 10%), and practicality (recoveries 90–104%). In addition, our developed aptasensor presented a great selectivity towards GA, compared to interfering substances commonly present in human serum, such as human serum albumin, urea, glucose, and bilirubin. Furthermore, the evaluation of the aptasensor performance against GA-spiked serum samples showed its probable applicability for clinical use. The developed PDA aptasensor demonstrated excellent sensitivity and selectivity towards GA detection with a simple and facile fabrication process. This proposed technique shows its potential application in GA measurement for improving the screening and management of diabetic patients in the future.
The Assembly of Flagella in Enteropathogenic Escherichia coli Requires the Presence of a Functional Type III Secretion System
Authors: Soria-Bustos Jorge , Saldaña-Ahuactzi Zeus , Samadder Partha , Yañez-Santos Jorge A. , Laguna Ygnacio Martínez , Cedillo-Ramírez María L. , Girón Jorge A.
Published: November 2022

In enteropathogenic Escherichia coli (EPEC), the production of flagella and the type III secretion system (T3SS) is activated in the presence of host cultured epithelial cells. The goal of this study was to investigate the relationship between expression of flagella and the T3SS. Mutants deficient in assembling T3SS basal and translocon components (ΔespA, ΔespB, ΔespD, ΔescC, ΔescN, and ΔescV), and in secreting effector molecules (ΔsepD and ΔsepL) were tested for flagella production under several growth conditions. The ΔespA mutant did not produce flagella in any condition tested, although fliC was transcribed. The remaining mutants produced different levels of flagella upon growth in LB or in the presence of cells but were significantly diminished in flagella production after growth in Dulbecco’s minimal essential medium. We also investigated the role of virulence and global regulator genes in expression of flagella. The ΔqseB and ΔqseC mutants produced abundant flagella only when growing in LB and in the presence of HeLa cells, indicating that QseB and QseC act as negative regulators of fliC transcription. The ΔgrlR, ΔperA, Δler, Δhns, and Δfis mutants produced low levels of flagella, suggesting these regulators are activators of fliC expression. These data suggest that the presence of an intact T3SS is required for assembly of flagella highlighting the existence in EPEC of a cross-talk between these two virulence-associated T3SSs.
FSAP Protects against Histone-Mediated Increase in Endothelial Permeability In Vitro
Authors: Cui Xue Yan , Stavik Benedicte , Thiede Bernd , Sandset Per Morten , Kanse Sandip M.
Published: November 2022

Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammation. Extracellular histones play a role in inflammation and the conversion of latent pro-FSAP into active FSAP. FSAP has been shown to regulate endothelial permeability, but the mechanisms are not clear. Here, we have investigated the effects of FSAP on endothelial permeability in vitro. A mixture of histones from calf thymus stimulated permeability, and the wild-type (WT) serine protease domain (SPD) of FSAP blocked this effect. WT–SPD–FSAP did not influence permeability on its own, nor that stimulated by thrombin or vascular endothelial growth factor (VEGF)-A165. Histones induced a large-scale rearrangement of the junction proteins VE-cadherin and zona occludens-1 from a clear junctional distribution to a diffuse pattern. The presence of WT–SPD–FSAP inhibited these changes. Permeability changes by histones were blocked by both TLR-2 and TLR4 blocking antibodies. Histones upregulated the expression of TLR-2, but not TLR-4, in HUVEC cells, and WT–SPD–FSAP abolished the upregulation of TLR-2 expression. An inactive variant, Marburg I (MI)–SPD–FSAP, did not have any of these effects. The inhibition of histone-mediated permeability may be an important function of FSAP with relevance to sepsis, trauma, and stroke and the need to be investigated further in in vivo experiments.
Antibiofilm Activity of Sundew Species against Multidrug-Resistant Escherichia coli Strains
Authors: Gerschler Sandy , Guenther Sebastian , Schulze Christian
Published: November 2022

Species of the genus Drosera, known for carnivorous plants, such as sundew, have been traditionally used for centuries as medicinal plants. Efficacy-determining compounds are naphthoquinones and flavonoids. Flavonoids possess a broad spectrum of bioactive properties, including biofilm inhibitory activity. Biofilms render antibiotics ineffective, contributing to the current rise in antimicrobial resistance. In this study, the biofilm inhibitory activity of two European sundew species (Drosera rotundifolia and Drosera intermedia) grown agriculturally in Germany and four commercial sundew products (declared as Drosera longifolia, Drosera sp. and Drosera planta trit.) against three multidrug-resistant Escherichia coli strains was tested. The aim of the study was to comparatively investigate the biofilm inhibitory potential of sundew species extracts grown locally in northern Germany and commercial sundew products. The minimum biofilm inhibitory concentration of the European sundew species was approx. 35 µg mL−1. In comparison, commercial sundew products ranged in concentration from 75 to 140 µg mL−1. Additionally, individual compounds isolated from European sundew were tested. Among these compounds, biofilm inhibitory activity was determined for four of the eight substances, with 2″-O-galloyl hyperoside standing out for its activity (38 µg mL−1). The whole plant extracts of Drosera rotundifolia and Drosera intermedia proved to be more effective than the commercial products and the single compounds in its biofilm inhibition activity against Escherichia coli strains. Sundew extracts may serve as a potential therapeutic approach for targeting biofilm production.