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21 pages, 2493 KiB  
Article
Assessment of Floral Nectar and Amino Acid Yield in Eight Landscape Trees for Enhanced Pollinator Food Resources in Urban Forests
by Sung-Joon Na, Ji-Min Park, Hae-Yun Kwon and Young-Ki Kim
Plants 2025, 14(13), 1924; https://doi.org/10.3390/plants14131924 - 23 Jun 2025
Viewed by 550
Abstract
Urban environments pose challenges for pollinators due to habitat loss and limited floral resources. However, green infrastructure, particularly street and ornamental trees, can play a critical role in supporting urban pollinator communities. In this study, we evaluated nectar volume, sugar content, and amino [...] Read more.
Urban environments pose challenges for pollinators due to habitat loss and limited floral resources. However, green infrastructure, particularly street and ornamental trees, can play a critical role in supporting urban pollinator communities. In this study, we evaluated nectar volume, sugar content, and amino acid composition across eight urban tree species commonly planted in South Korea. Using standardized productivity metrics at the flower, tree, and hectare scales, we compared their nutritional contributions. Our results revealed substantial interspecific differences in nectar quantity and composition. Tilia amurensis, Heptacodium miconioides, Aesculus turbinata, and Wisteria floribunda exhibited high nectar yields or amino acid productivity, whereas species such as Cornus kousa, though lower in nutritional yield, may offer complementary value due to their distinct flowering periods or other phenological traits. These findings underscore the importance of selecting tree species not only for aesthetic value but also for ecological function, providing an evidence-based approach to pollinator-friendly urban biodiversity planning and landscape management. Full article
(This article belongs to the Special Issue Plants and Their Floral Visitors in the Face of Global Change)
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13 pages, 2086 KiB  
Article
Investigation of N-Acetyllactosamine and N,N-Diacetyllactosamine Residues of Seminal Plasma Prolactin-Induced Protein as Ligands Recognized by Galectin-3
by Anna Kałuża, Katarzyna Trzęsicka, Damian Drzyzga and Mirosława Ferens-Sieczkowska
Int. J. Mol. Sci. 2024, 25(24), 13432; https://doi.org/10.3390/ijms252413432 - 15 Dec 2024
Viewed by 891
Abstract
Prolactin induced-protein (PIP) has been found to be rich in immunomodulatory epitopes, including N-acetyllactosamine (LacNAc) and N,N-diacetyllactosamine (LacdiNAc) residues, which may constitute ligands for galecin-3 (Gal-3). In the current study, we aimed to investigate the reactivity of galactose- and [...] Read more.
Prolactin induced-protein (PIP) has been found to be rich in immunomodulatory epitopes, including N-acetyllactosamine (LacNAc) and N,N-diacetyllactosamine (LacdiNAc) residues, which may constitute ligands for galecin-3 (Gal-3). In the current study, we aimed to investigate the reactivity of galactose- and N-acetylgalactosamine-specific lectins with human seminal plasma PIP. Subsequently, we examined the direct interaction between seminal plasma PIP and galectin-3, and next analyzed whether there are any differences in the interaction associated with impaired semen parameters. The reactivity of terminal galactose-presenting glycans in seminal plasma PIP with Ricinus communis agglutinin I in the asthenozoospermic group was significantly higher compared to the normozoospermic fertile subjects. Investigating the reactivity of Wisteria floribunda lectin with PIP glycans, we found likewise significantly higher relative reactivity in the normozoospermic infertile as well as the oligoasthenozoopermic group compared to the control group. These results are related to the expression of LacdiNAc epitopes in the oligosaccharide chain of PIP. Finally, we observed that PIP reactivity with Wisteria floribunda lectin correlates positively with the interaction between galectin-3 and PIP in the seminal plasma. This can suggest that LacdiNAc residues are engaged in the interaction between PIP and galectin-3. Full article
(This article belongs to the Special Issue Galectins (Gals))
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30 pages, 3020 KiB  
Article
The Evolution of Wisteria Vein Mosaic Virus: A Case Study Approach to Track the Emergence of New Potyvirus Threats
by Massimiliano Morelli, Giusy D’Attoma, Pasquale Saldarelli and Angelantonio Minafra
Pathogens 2024, 13(11), 1001; https://doi.org/10.3390/pathogens13111001 - 15 Nov 2024
Cited by 2 | Viewed by 1227
Abstract
Wisteria vein mosaic virus (WVMV, Potyvirus wisteriae), a virus belonging to the genus Potyvirus, is responsible for Wisteria vein mosaic disease (WMD), a severe disease that affects Wisteria, a genus of garden plants acclaimed worldwide. Although probably originating in the [...] Read more.
Wisteria vein mosaic virus (WVMV, Potyvirus wisteriae), a virus belonging to the genus Potyvirus, is responsible for Wisteria vein mosaic disease (WMD), a severe disease that affects Wisteria, a genus of garden plants acclaimed worldwide. Although probably originating in the Far East, WVMV infection was first reported in the US, and subsequently in numerous countries. Following the first molecular detection of an Italian isolate, WVMV Bari, its full-length genome was achieved using NGS barcoding technology. A PhyML phylogenetic analysis, supported by clustering algorithm validation, identified a clear separation between two phylogroups. One major clade comprised WVMV strains isolated from Wisteria spp. A second clade grouped three highly divergent strains, at the borderline species threshold, all found in non-wisteria hosts. Relying on a Relative Time Dated Tips (RTDT) molecular clock, the first emergence of WVMV clades has been traced back to around the 17th century. A network inference analysis confirmed the sharp separation between the two host-related phylogroups, also highlighting the presence of potential intermediate variants. Inter-population genetic parameters revealed a very high genetic differentiation in both populations, which was made reliable by statistically significant permutation tests. The migrant number (Nm) and fixation index (FST) evidenced a restricted gene flow and strong population structures. According to the dN/dS ratio and negative neutrality tests, it was derived that purifying selection at the expense of non-silent variants is underway within WVMV populations. Targeting WVMV evolutionary traits, the present effort raised interesting questions about the underestimated potential of this culpably neglected species to spread in economically relevant crops. The main intention of our study is, therefore, to propose an evolution-based analysis approach that serves as a case study to investigate how other potyviruses or newly emerging viruses may spread. Full article
(This article belongs to the Special Issue The Plant RNA Viruses)
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16 pages, 3913 KiB  
Article
Characterization of a Putative New Member of the Genus Potyvirus from Kudzu (Pueraria montana var. lobata) in Mississippi
by Nina Aboughanem-Sabanadzovic, Ronald Christian Stephenson, Thomas W. Allen, Alan Henn, William F. Moore, Amanda Lawrence and Sead Sabanadzovic
Viruses 2023, 15(11), 2145; https://doi.org/10.3390/v15112145 - 25 Oct 2023
Cited by 1 | Viewed by 2061
Abstract
Kudzu (Pueraria montana var. lobata), a plant native to Southeastern Asia, has become a major noxious weed covering millions of hectares in the Southern United States. A kudzu patch displaying virus-like symptoms located in Ackerman, northeastern Mississippi (MS), was used as [...] Read more.
Kudzu (Pueraria montana var. lobata), a plant native to Southeastern Asia, has become a major noxious weed covering millions of hectares in the Southern United States. A kudzu patch displaying virus-like symptoms located in Ackerman, northeastern Mississippi (MS), was used as a source for virus isolation and characterization involving mechanical and vector transmission, ultrastructural observation, surveys, Sanger and high-throughput genome sequencing, and sequence analyses. The results revealed the presence of a new potyvirus in infected kudzu, closely related to wisteria vein mosaic virus (WVMV) and provisionally named kudzu chlorotic ring blotch virus (KudCRBV). Genome features and pairwise comparison with six WVMV genomes currently available in GenBank and three additional isolates from MS sequenced in this work suggest that KudCRBV is likely a member of a new species in the genus Potyvirus. Furthermore, under experimental conditions, KudCRBV was successfully transmitted by cotton and potato aphids and mechanically to soybean and beans. A state-wide survey revealed several kudzu patches infected by the virus in northern MS. Full article
(This article belongs to the Special Issue A Tribute to Giovanni P. Martelli)
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24 pages, 4612 KiB  
Article
Molecular Evidence for the Presence of Wisteria Vein Mosaic Virus in Italy: Shedding Light on Genetic Diversity and Evolutionary Dynamics of Virus Geographic Populations
by Giusy D’Attoma, Angelantonio Minafra, Pasquale Saldarelli and Massimiliano Morelli
Agriculture 2023, 13(5), 1090; https://doi.org/10.3390/agriculture13051090 - 19 May 2023
Cited by 3 | Viewed by 3386
Abstract
Wisteria vein mosaic virus (WVMV) is a member of the genus Potyvirus, found to be associated with the Wisteria mosaic disease (WMD). In 2022, severe symptoms resembling WMD were observed on the foliage of a Chinese wisteria (Wisteria sinensis) tree [...] Read more.
Wisteria vein mosaic virus (WVMV) is a member of the genus Potyvirus, found to be associated with the Wisteria mosaic disease (WMD). In 2022, severe symptoms resembling WMD were observed on the foliage of a Chinese wisteria (Wisteria sinensis) tree growing in Apulia (Italy). The presence of WVMV was ascertained by RT-PCR using the universal degenerate primers NIb2F/NIb3R in the NIb gene. Next, we derived the complete sequence of the CP gene. MAFFT pairwise alignment of the two target regions showed a high amino acid sequence identity of isolate Bari with other WVMV isolates, confirming they belonged to the same species. NIb phylogenetic analysis placed WVMV Bari within the lineage identified in the genus Potyvirus as the bean common mosaic virus supergroup. Closer analysis based on the CP gene showed that WVMV Bari was part of a sub-clade gathering all WVMV isolates within a larger clade clustering closely related species. An exploratory analysis of the genetic diversity and possible mechanisms underlying the evolution of geographic populations of WVMV was attempted. The analysis was based on the N-terminal coding region of CP, available for 20 isolates from Europe, Asia, and Oceania. A high diversity, mainly found in the European population, led to the identification of 16 different haplotypes. Based on the dN/dS ratio, the target region appears to be under negative selective pressure. Neutrality tests indicated a potential population expansion in Europe and a recent decrease in Asia. The two populations exhibited a high level of gene flow. We found that WVMV Bari may have originated from a recombination event in the NIb gene. To date, the presence of WVMV had never been reported on W. sinensis in Italy, and no molecular information was available on any Italian isolate. Our report draws attention to the further spread of WVMV in the European territory and its rising threat to the ornamental nursery sector. Full article
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9 pages, 946 KiB  
Article
Activation of a Sweet Taste Receptor by Oleanane-Type Glycosides from Wisteria sinensis
by Samir Hobloss, Antoine Bruguière, David Pertuit, Tomofumi Miyamoto, Chiaki Tanaka, Christine Belloir, Marie-Aleth Lacaille-Dubois, Loïc Briand and Anne-Claire Mitaine-Offer
Molecules 2022, 27(22), 7866; https://doi.org/10.3390/molecules27227866 - 15 Nov 2022
Cited by 2 | Viewed by 2350
Abstract
The phytochemical study of Wisteria sinensis (Sims) DC. (Fabaceae), commonly known as the Chinese Wisteria, led to the isolation of seven oleanane-type glycosides from an aqueous-ethanolic extract of the roots. Among the seven isolated saponins, two have never been reported before: 3-O [...] Read more.
The phytochemical study of Wisteria sinensis (Sims) DC. (Fabaceae), commonly known as the Chinese Wisteria, led to the isolation of seven oleanane-type glycosides from an aqueous-ethanolic extract of the roots. Among the seven isolated saponins, two have never been reported before: 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl-22-O-acetylolean-12-ene-3β,16β,22β,30-tetrol, and 3-O-β-D-xylopyranosyl-(1→2)-β-D-glucuronopyranosylwistariasapogenol A. Based on the close structures between the saponins from W. sinensis, and the glycyrrhizin from licorice, the stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated. Full article
(This article belongs to the Special Issue Analysis of Phytochemical Components)
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19 pages, 4613 KiB  
Article
Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis
by Barbara Sitaš, Mihaela Bobić-Rasonja, Goran Mrak, Sara Trnski, Magdalena Krbot Skorić, Darko Orešković, Vinka Knezović, Željka Petelin Gadže, Zdravko Petanjek, Goran Šimić, Danijela Kolenc and Nataša Jovanov Milošević
Int. J. Mol. Sci. 2022, 23(15), 8197; https://doi.org/10.3390/ijms23158197 - 25 Jul 2022
Cited by 7 | Viewed by 3336
Abstract
The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. [...] Read more.
The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy. Full article
(This article belongs to the Special Issue Neuropathological Advances in Brain Disorders from MNS2023)
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15 pages, 1649 KiB  
Article
Development and Evaluation of a Robust Sandwich Immunoassay System Detecting Serum WFA-Reactive IgA1 for Diagnosis of IgA Nephropathy
by Yuta Uenoyama, Atsushi Matsuda, Kazune Ohashi, Koji Ueda, Misaki Yokoyama, Takuya Kyoutou, Kouji Kishi, Youichi Takahama, Masaaki Nagai, Takaaki Ohbayashi, Osamu Hotta and Hideki Matsuzaki
Int. J. Mol. Sci. 2022, 23(9), 5165; https://doi.org/10.3390/ijms23095165 - 5 May 2022
Cited by 4 | Viewed by 2516
Abstract
Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich [...] Read more.
Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich immunoassay system for detecting aberrant glycosylated IgA1, using Wisteria floribunda agglutinin (WFA) and anti-IgA1 monoclonal antibody. The diagnostic performance as an IgAN marker was evaluated. The usefulness of WFA for immunoassays was investigated by lectin microarray. A reliable standard for quantitative immunoassay measurements was designed by modifying a purified IgA1 substrate. A validation study using multiple serum specimens was performed using the established WFA-antibody sandwich automated immunoassay. Lectin microarray results showed that WFA specifically recognized N-glycans of agglutinated IgA1 in IgAN patients. The constructed IgA1 standard exhibited a wide dynamic range and high reactivity. In the validation study, serum WFA-reactive IgA1 (WFA+-IgA1) differed significantly between healthy control subjects and IgAN patients. The findings indicate that WFA is a suitable lectin that specifically targets abnormal agglutinated IgA1 in serum. We also describe an automated immunoassay system for detecting WFA+-IgA1, focusing on N-glycans. Full article
(This article belongs to the Special Issue Glycobiology-Based Drug Development)
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16 pages, 1859 KiB  
Article
Interprofessional and Intraprofessional Communication about Older People’s Medications across Transitions of Care
by Elizabeth Manias, Tracey Bucknall, Robyn Woodward-Kron, Carmel Hughes, Christine Jorm, Guncag Ozavci and Kathryn Joseph
Int. J. Environ. Res. Public Health 2021, 18(8), 3925; https://doi.org/10.3390/ijerph18083925 - 8 Apr 2021
Cited by 10 | Viewed by 6151
Abstract
Communication breakdowns contribute to medication incidents involving older people across transitions of care. The purpose of this paper is to examine how interprofessional and intraprofessional communication occurs in managing older patients’ medications across transitions of care in acute and geriatric rehabilitation settings. An [...] Read more.
Communication breakdowns contribute to medication incidents involving older people across transitions of care. The purpose of this paper is to examine how interprofessional and intraprofessional communication occurs in managing older patients’ medications across transitions of care in acute and geriatric rehabilitation settings. An ethnographic design was used with semi-structured interviews, observations and focus groups undertaken in an acute tertiary referral hospital and a geriatric rehabilitation facility. Communication to manage medications was influenced by the clinical context comprising the transferring setting (preparing for transfer), receiving setting (setting after transfer) and ‘real-time’ (simultaneous communication). Three themes reflected these clinical contexts: dissemination of medication information, safe continuation of medications and barriers to collaborative communication. In transferring settings, nurses and pharmacists anticipated communication breakdowns and initiated additional communication activities to ensure safe information transfer. In receiving settings, all health professionals contributed to facilitating safe continuation of medications. Although health professionals of different disciplines sometimes communicated with each other, communication mostly occurred between health professionals of the same discipline. Lack of communication with pharmacists occurred despite all health professionals acknowledging their important role. Greater levels of proactive preparation by health professionals prior to transfers would reduce opportunities for errors relating to continuation of medications. Full article
(This article belongs to the Special Issue Resilience and Improvisation at the Frontlines of Healthcare)
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14 pages, 1838 KiB  
Article
Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup
by Nobuharu Tamaki, Masayuki Kurosaki, Yuka Takahashi, Yoshie Itakura, Sakura Kirino, Kento Inada, Koji Yamashita, Shuhei Sekiguchi, Yuka Hayakawa, Leona Osawa, Mayu Higuchi, Kenta Takaura, Chiaki Maeyashiki, Shun Kaneko, Yutaka Yasui, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Rohit Loomba and Namiki Izumi
Int. J. Mol. Sci. 2021, 22(1), 40; https://doi.org/10.3390/ijms22010040 - 22 Dec 2020
Cited by 8 | Viewed by 2854
Abstract
Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this [...] Read more.
Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1–16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7–8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population. Full article
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17 pages, 3024 KiB  
Article
Reconsideration of the Semaphorin-3A Binding Motif Found in Chondroitin Sulfate Using Galnac4s-6st-Knockout Mice
by Satomi Nadanaka, Shinji Miyata, Bai Yaqiang, Jun-ichi Tamura, Osami Habuchi and Hiroshi Kitagawa
Biomolecules 2020, 10(11), 1499; https://doi.org/10.3390/biom10111499 - 30 Oct 2020
Cited by 34 | Viewed by 3939
Abstract
The chondroitin sulfate (CS)-rich dense extracellular matrix surrounding neuron cell bodies and proximal dendrites in a mesh-like structure is called a perineuronal net (PNN). CS chains in PNNs control neuronal plasticity by binding to PNN effectors, semaphorin-3A (Sema3A) and orthodenticle homeobox 2. Sema3A [...] Read more.
The chondroitin sulfate (CS)-rich dense extracellular matrix surrounding neuron cell bodies and proximal dendrites in a mesh-like structure is called a perineuronal net (PNN). CS chains in PNNs control neuronal plasticity by binding to PNN effectors, semaphorin-3A (Sema3A) and orthodenticle homeobox 2. Sema3A recognizes CS-containing type-E disaccharide units (sulfated at O-4 and O-6 of N-acetylgalactosamine). Type-E disaccharide units are synthesized by N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST). In this study, we demonstrated that Sema3A accumulates in the PNNs surrounding parvalbumin cells, even in mice deficient in GalNAc4S-6ST. In addition, there were no differences in the number and structure of PNNs visualized by Cat316 antibody and Wisteria floribunda lectin, which recognize CS chains, between wild type and GalNAc4S-6ST knockout mice. Therefore, we re-examined the Sema3A binding motif found in CS chains using chemically synthesized CS tetrasaccharides. As a result, we found that non-sulfated GalNAc residues at the non-reducing termini of CS chains are required for the binding of Sema3A. Full article
(This article belongs to the Special Issue Structural and Functional Approach to the Glycan Diversity)
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16 pages, 2300 KiB  
Article
Post-Treatment M2BPGi Level and the Rate of Autotaxin Reduction are Predictive of Hepatocellular Carcinoma Development after Antiviral Therapy in Patients with Chronic Hepatitis C
by Kazuya Takemura, Etsuko Takizawa, Akihiro Tamori, Mika Nakamae, Hiroshi Kubota, Sawako Uchida-Kobayashi, Masaru Enomoto, Norifumi Kawada and Masayuki Hino
Int. J. Mol. Sci. 2020, 21(12), 4517; https://doi.org/10.3390/ijms21124517 - 25 Jun 2020
Cited by 3 | Viewed by 2873
Abstract
Patients with chronic hepatitis C virus (HCV) develop hepatocellular carcinoma (HCC) regardless of achieving a sustained viral response (SVR). Because advanced liver fibrosis is a powerful risk factor for HCC, we analyzed the association between autotaxin (ATX), a liver fibrosis marker, and post-SVR [...] Read more.
Patients with chronic hepatitis C virus (HCV) develop hepatocellular carcinoma (HCC) regardless of achieving a sustained viral response (SVR). Because advanced liver fibrosis is a powerful risk factor for HCC, we analyzed the association between autotaxin (ATX), a liver fibrosis marker, and post-SVR HCC development within 3 years after antiviral treatment. We included 670 patients with HCV who received direct-acting antivirals, achieved SVR and were followed up for at least 6 months (270 of them were followed up for 3 years or more). We measured serum ATX levels before treatment and 12/24 weeks after treatment. The diagnosis of HCC was based on imaging modalities, such as dynamic computed tomography and dynamic magnetic resonance imaging and/or liver biopsy. The present study revealed that high levels of serum ATX predicted post-SVR HCC development (area under the receiver operating characteristic: 0.70–0.76). However, Wisteria floribunda agglutinin positive Mac-2 binding protein (M2BPGi), another liver fibrosis marker, was a more useful predictive marker especially post-treatment according to a multivariate analysis. Patients with a high rate of ATX reduction before and after antiviral treatment did not develop HCC regardless of high pretreatment ATX levels. In conclusion, post-treatment M2BPGi level and the combination of pretreatment ATX levels and rate of ATX reduction were useful predictive markers for post-SVR HCC development in patients with chronic HCV infection. Full article
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11 pages, 1495 KiB  
Article
Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein but not α-fetoprotein as a Long-Term Hepatocellular Carcinoma Predictor
by Leona Osawa, Nobuharu Tamaki, Masayuki Kurosaki, Sakura Kirino, Keiya Watakabe, Wan Wang, Mao Okada, Takao Shimizu, Mayu Higuchi, Kenta Takaura, Hitomi Takada, Shun Kaneko, Yutaka Yasui, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi, Nobuyuki Enomoto and Namiki Izumi
Int. J. Mol. Sci. 2020, 21(10), 3640; https://doi.org/10.3390/ijms21103640 - 21 May 2020
Cited by 7 | Viewed by 3070
Abstract
Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis [...] Read more.
Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 ± 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA±M2BP) ≥ 1.85 and α-fetoprotein (AFP) ≥ 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA±M2BP ≥ 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68–205) but not AFP. Among patients with WFA±M2BP ≥ 1.85 at SVR24, 42% had WFA±M2BP < 1.85 at 1 year after SVR24 (WFA±M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA±M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC. Full article
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10 pages, 702 KiB  
Article
Use of the Serum Wisteria floribunda Agglutinin-Positive Mac2 Binding Protein as a Marker of Gastroesophageal Varices and Liver-Related Events in Chronic Hepatitis C Patients
by Tsuguru Hayashi, Nobuharu Tamaki, Masayuki Kurosaki, Wan Wang, Mao Okada, Mayu Higuchi, Kenta Takaura, Hitomi Takada, Yutaka Yasui, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Masaru Harada and Namiki Izumi
Diagnostics 2020, 10(3), 173; https://doi.org/10.3390/diagnostics10030173 - 22 Mar 2020
Cited by 10 | Viewed by 3776
Abstract
Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 [...] Read more.
Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 consecutive chronic hepatitis C patients. The correlation between the grades of GEV and fibrosis markers and the subsequent occurrence of liver-related and fibrosis markers were examined. Results: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+–M2BP) levels increased according to the grade of GEV (3.4 (0.2–18.6) for no GEV, 7.9 (1.8–20.0) for small GEV, and 11.4 (4.0–20.0) for large GEV; p < 0.001). The diagnostic accuracy of the WFA+–M2BP was superior compared to other serum fibrosis markers, and WFA+–M2BP was an independent predictor of GEV in the multivariate analysis. Furthermore, the cumulative incidence of liver-related events at one year was 2.3% in patients with WFA+–M2BP levels ≤ 7.0 and 37.5% in patients with WFA+–M2BP levels > 7.0 (p < 0.001). WFA+–M2BP > 7.0 was a significant predictive factor for liver-related events (Hazard ratio 6.7, p = 0.004) independent of Child–Pughclass. Conclusions: WFA+–M2BP could be used to estimate the presence and grade of GEV and is linked to liver-related events in chronic hepatitis C patients. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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Review
Novel Biomarkers of Hepatitis B and Hepatocellular Carcinoma: Clinical Significance of HBcrAg and M2BPGi
by Ian Baudi, Takako Inoue and Yasuhito Tanaka
Int. J. Mol. Sci. 2020, 21(3), 949; https://doi.org/10.3390/ijms21030949 - 31 Jan 2020
Cited by 33 | Viewed by 11801
Abstract
The hepatitis B virus (HBV) cannot be removed completely from infected hepatocytes, owing to the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), predicting HCC development in high-risk patients with [...] Read more.
The hepatitis B virus (HBV) cannot be removed completely from infected hepatocytes, owing to the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), predicting HCC development in high-risk patients with high viral replicative activity or advanced fibrosis is important. Novel serological biomarkers reflect intrahepatic viral replicative activity or the progression of liver fibrosis, indicating non-invasive alternatives to liver biopsy: (1) Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients, a decrease in HBcrAg is associated with favorable outcomes. HBcrAg can predict HCC occurrence or recurrence. (2) Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. An increase in M2BPGi in CHB patients is related to the progression of liver fibrosis and high potential (risk) of HCC development. Here, we describe the clinical applications of HBcrAg and M2BPGi in CHB patients. Additionally, because new potential therapeutic agents that eliminate intrahepatic cccDNA are being developed, monitoring of HBcrAg or M2BPGi might be suitable for evaluating therapeutic effects and the clinical outcomes. In conclusion, these would be appropriate surrogate markers for predicting disease progression. Full article
(This article belongs to the Special Issue Molecular Pathogenesis of Viral Hepatitis and Liver Cancer)
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