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Keywords = chitinase 3-like 1 protein

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10 pages, 270 KiB  
Article
Maresin 1 and CHI3L1 Levels Exhibit Opposing Trends and Correlations with Renal Dysfunction in Diabetic Nephropathy
by Aykut Bulu, Erhan Onalan, Burkay Yakar, Gulay Bulu, Senanur Onalan Yıldırım, Mehmet Ferit Gursu, Ugur Kaplankaya, Emir Donder and Tugce Kaymaz
Medicina 2025, 61(7), 1247; https://doi.org/10.3390/medicina61071247 - 10 Jul 2025
Viewed by 273
Abstract
Background and Objectives: This study aimed to investigate the relationship between Maresin-1 (MaR1), Chitinase-3-like protein 1 (CHI3L1), and inflammatory as well as hematological markers in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Materials and Methods: This cross-sectional [...] Read more.
Background and Objectives: This study aimed to investigate the relationship between Maresin-1 (MaR1), Chitinase-3-like protein 1 (CHI3L1), and inflammatory as well as hematological markers in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Materials and Methods: This cross-sectional study included 90 participants divided into three groups: healthy controls (n = 30), patients with T2DM (n = 30), and patients with diabetic nephropathy (n = 30). The serum levels of MaR1 and CHI3L1 were measured using ELISA. Biochemical and hematological parameters were also assessed. Statistical comparisons were conducted using non-parametric tests, and correlations were analyzed via Spearman correlation. Results: Serum MaR1 levels were significantly higher in DN patients compared to both T2DM patients and controls (p < 0.01), while CHI3L1 levels were significantly lower in the DN group compared to controls (p = 0.007). MaR1 showed a positive correlation with CRP, BUN, and creatinine, and a negative correlation with GFR. CHI3L1 levels were positively correlated with GFR and negatively with BUN. Inflammatory markers such as CRP were elevated in the diabetic groups, while no significant differences were found in NLR values. Conclusions: Elevated MaR1 levels in DN patients and their correlation with renal dysfunction markers suggest that MaR1 may serve as a potential prognostic biomarker in diabetic nephropathy. The unexpected decrease in CHI3L1 levels in DN patients indicates the need for further research to clarify their role. These findings indicated that MaR1 and CHI3L1 should be further investigated in future studies as indicators for the early detection and monitoring of diabetic complications. Full article
(This article belongs to the Section Endocrinology)
19 pages, 785 KiB  
Article
HE4 as a Prognostic Biomarker of Major Adverse Cardiovascular Events in Patients with Abdominal Aortic Aneurysm: A Canadian Prospective Observational Study
by Hamzah Khan, Abdelrahman Zamzam, Farah Shaikh, Muhammad Mamdani, Gustavo Saposnik and Mohammad Qadura
Biomedicines 2025, 13(7), 1562; https://doi.org/10.3390/biomedicines13071562 - 26 Jun 2025
Viewed by 461
Abstract
Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the proteolytic breakdown of the extracellular matrix. A clinical biomarker is needed for risk stratification and prognosis. Methods: In this single-center, 5-year observational study, 452 patients were enrolled: 343 with [...] Read more.
Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the proteolytic breakdown of the extracellular matrix. A clinical biomarker is needed for risk stratification and prognosis. Methods: In this single-center, 5-year observational study, 452 patients were enrolled: 343 with AAA (≥3 cm), and 109 controls (<3 cm). Plasma levels of six inflammatory proteins (human epididymis protein 4 (HE4), matrix metalloproteinase (MMP) 1 and 3, cathepsin S, chitinase 3 like-1, cathepsin S, and B-cell activating factor (BAFF)) were quantified at baseline. Patients were followed for a total of 5 years (60 months), and major adverse cardiovascular events (MACEs, defined as the composite of myocardial infarction, cerebrovascular attack, and cardiovascular-related death) were recorded. A Cox proportional hazard model was created using biomarker levels, age, sex, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, and coronary artery disease to determine whether the baseline levels of these proteins were associated with MACEs over 5 years. Results: HE4, MMP-3, BAFF, and cathepsin S levels were significantly elevated in AAA patients compared to controls (all p < 0.05). HE4/WFDC2, MMP-3, and Chitinase 3-like 1 were significantly linearly associated with AAA diameter at baseline. With every normalized unit increase in HE4/WFDC2, MMP-3, and Chitinase 3-like 1, there was an increase in abdominal aortic diameter by 0.154 (95% CI: 0.032–0.276, p = 0.013), 0.186 (95% CI: 0.064–0.309, p = 0.003), and 0.231 (0.110–0.353, p < 0.001) centimeters, respectively. Among patients with AAA, elevated HE4 was associated with higher risk of MACEs (adjusted HR 1.249; 95% CI: 1.057–1.476; p = 0.009). Patients with high baseline HE4 (≥9.338 ng/mL) had significantly lower freedom from MACEs at 5 years (76.7% vs. 84.8%, p = 0.022). Conclusions: HE4 may be a potential prognostic biomarker that can be used to risk stratify patients with AAA to better personalize treatment strategies to reduce adverse events. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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18 pages, 6802 KiB  
Article
Fh15 Reduces Colonic Inflammation and Leukocyte Infiltration in a Dextran Sulfate Sodium-Induced Ulcerative Colitis Mouse Model
by María Del Mar Figueroa-Gispert, Claudia M. Ramos-Lugo, Carlimar Ocasio-Malavé, Rizaldy P. Scott, Jared T. Ahrendsen, Mercedes Gomez-Samblas, Antonio Osuna, Stephanie M. Dorta-Estremera and Ana M. Espino
Cells 2025, 14(11), 799; https://doi.org/10.3390/cells14110799 - 29 May 2025
Viewed by 784
Abstract
Ulcerative colitis (UC) is the most prevalent inflammatory bowel disease (IBD) in the USA. Current treatments present clinical limitations, underscoring the need for innovative therapeutics that promote an anti-inflammatory immune response. This study evaluates the anti-inflammatory potential of Fh15, a recombinant Fasciola hepatica [...] Read more.
Ulcerative colitis (UC) is the most prevalent inflammatory bowel disease (IBD) in the USA. Current treatments present clinical limitations, underscoring the need for innovative therapeutics that promote an anti-inflammatory immune response. This study evaluates the anti-inflammatory potential of Fh15, a recombinant Fasciola hepatica fatty acid binding protein, in a DSS-induced UC mouse model. Our results demonstrated that Fh15 treatment significantly ameliorated the severity of colitis by reducing the disease activity index (DAI) and histopathological scores. Moreover, Fh15 also decreased the serum levels of myeloperoxidase (MPO) and chitinase-3-like protein 1 (CHI3L1), and the expression of S100A9, a calcium and zinc binding protein, which is an important marker for the pathogenesis of UC. Furthermore, Fh15 downregulated pro-inflammatory cytokines TNFα and IL-1β in the distal colon, suggesting modulation of macrophage activity. Immunohistochemistry analysis revealed significantly reduced neutrophil and macrophage infiltration in UC Fh15-treated mice. These findings highlight the therapeutic potential of Fh15 for UC, as it modulates inflammatory responses, reduces leukocyte infiltration, and preserves colon integrity. Full article
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19 pages, 7090 KiB  
Article
Implications of Chitinase 3-like 1 Protein in the Pathogenesis of Multiple Sclerosis in Autopsied Brains and a Murine Model
by Yoshio Bando, Yasuhiro Suzuki, Chisato Murakami, Takashi Kimura and Osamu Yahara
Int. J. Mol. Sci. 2025, 26(9), 4160; https://doi.org/10.3390/ijms26094160 - 27 Apr 2025
Viewed by 848
Abstract
Chitinase-3-like protein 1 (CHI3L1) has been implicated in multiple sclerosis (MS) pathology, yet its precise role remains unclear. To elucidate its involvement, we performed proteomic analysis of cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients using two-dimensional difference gel electrophoresis (2D-DIGE). CHI3L1 emerged [...] Read more.
Chitinase-3-like protein 1 (CHI3L1) has been implicated in multiple sclerosis (MS) pathology, yet its precise role remains unclear. To elucidate its involvement, we performed proteomic analysis of cerebrospinal fluid (CSF) from relapsing-remitting MS (RRMS) patients using two-dimensional difference gel electrophoresis (2D-DIGE). CHI3L1 emerged as the most upregulated protein in recurrent RRMS. ELISA confirmed significantly elevated CHI3L1 levels in recurrent RRMS and secondary progressive MS (SPMS) patients, with levels decreasing in steroid responders but increasing in non-responders. Immunohistochemistry of MS brain autopsies revealed CHI3L1 expression predominantly in mature oligodendrocytes. In an experimental autoimmune encephalomyelitis (EAE) model, CHI3L1 was highly expressed in the spinal cord, particularly in oligodendrocytes and microglia/macrophages. Functional studies demonstrated that recombinant CHI3L1 (rCHI3L1) protected oligodendrocytes from LPC-induced cell death by attenuating ER stress (GRP78, ORP150). Moreover, rCHI3L1 counteracted IFN-β- and PSL-mediated inhibition of oligodendrocyte differentiation. In microglia, rCHI3L1 suppressed LPS-induced proinflammatory markers (IL-1β, iNOS). In vivo, rCHI3L1 administration significantly mitigated EAE severity by reducing gliosis, demyelination, and axonal degeneration. These findings highlight CHI3L1 as a critical modulator of neuroinflammation and oligodendrocyte survival, positioning it as a promising therapeutic target for MS. Full article
(This article belongs to the Special Issue Molecular Insights into Multiple Sclerosis)
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23 pages, 2906 KiB  
Article
The Legacy of COVID-19 in Breast Milk: The Association of Elevated Anti-Inflammatory and Antimicrobial Proteins with Vaccination or Infection
by Felicia Trofin, Petru Cianga, Daniela Constantinescu, Luminița Smaranda Iancu, Roxana Irina Iancu, Diana Păduraru, Eduard Vasile Nastase, Elena Roxana Buzilă, Cătălina Luncă, Corina Maria Cianga and Olivia Simona Dorneanu
Curr. Issues Mol. Biol. 2025, 47(3), 182; https://doi.org/10.3390/cimb47030182 - 11 Mar 2025
Cited by 1 | Viewed by 1504
Abstract
Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials [...] Read more.
Background: Breast milk is a rich source of antimicrobial and anti-inflammatory compounds, owing to its diverse array of bioactive molecules. This study explores the presence and activity of natural antimicrobial agents in breast milk, particularly in the context of the SARS-CoV-2 pandemic. Materials and Methods: Breast milk samples were collected from 50 breastfeeding mothers, including those who had either been vaccinated against SARS-CoV-2 or had recovered from the infection. These samples were compared with a control group consisting of 10 unvaccinated mothers with no history of COVID-19. Key antimicrobial and immune-regulatory proteins—lactoferrin, lactadherin, furin, tenascin C, granzyme B, and chitinase 3-like 1—were quantified using the Luminex multiplex analyzer. Results and Discussion: All targeted biomarkers were detected in breast milk, providing insights into the immune profile transferred to infants following COVID-19 infection or vaccination. These bioactive molecules highlight breastfeeding’s role in providing passive immunity and antimicrobial protection. The protein levels were found to be influenced by factors such as maternal inflammation, infant age, delivery mode, and parity, emphasizing the dynamic interaction between maternal immunity, lactation biology, and infant development. Conclusion: Breastfeeding serves as a powerful anti-SARS-CoV-2 defense mechanism, supported by the activity of lactoferrin, lactadherin, and furin, reinforcing its critical role in child health. Full article
(This article belongs to the Special Issue The Role of Bioactives in Inflammation)
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20 pages, 404 KiB  
Review
CHI3L1 in Multiple Sclerosis—From Bench to Clinic
by Izabela Jatczak-Pawlik, Anna Jurewicz, Małgorzata Domowicz, Alicja Ewiak-Paszyńska and Mariusz Stasiołek
Cells 2024, 13(24), 2086; https://doi.org/10.3390/cells13242086 - 17 Dec 2024
Cited by 4 | Viewed by 1542
Abstract
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is [...] Read more.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) with a complex and not fully understood etiopathological background involving inflammatory and neurodegenerative processes. CHI3L1 has been implicated in pathological conditions such as inflammation, injury, and neurodegeneration, and is likely to play a role in the physiological development of the CNS. CHI3L1 is primarily produced by CNS macrophages, microglia, and activated astrocytes. The CHI3L1 expression pattern in MS lesions might support the important role of astrocytes in modulating inflammatory processes in this disease. The potential applications of CHI3L1 as a biomarker in MS are multifactorial. The measurement of CHI3L1 in body fluids might find its role in the early diagnosis of MS. In further stages, the monitoring of CHI3L1 levels might provide information on disease severity and progression, enabling a better adjustment of therapeutic strategies. Importantly, CHI3L1 might potentially serve as a marker of ongoing glial activation, reflecting the dynamic response of the CNS cells to the inflammatory processes in MS. Although preliminary findings have been promising, further research is needed to validate the utility of CHI3L1 measurements in the diagnosis and prediction of the progression of MS. Additionally, comparisons with other biomarkers might be useful in clinical practice. Full article
(This article belongs to the Special Issue Emerging Roles of Glial Cells in Human Health and Disease)
14 pages, 933 KiB  
Article
Effect of Vitamin D Supplementation on Inflammatory Markers in Obese Patients with Acute and Chronic Orthopedic Conditions
by Michał Gawryjołek, Michał Wiciński, Maria Zabrzyńska, Jakub Ohla and Jan Zabrzyński
Nutrients 2024, 16(21), 3735; https://doi.org/10.3390/nu16213735 - 31 Oct 2024
Viewed by 1662
Abstract
Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included [...] Read more.
Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included in the study and were divided into two groups based on their medical condition: acute orthopedic diseases and chronic orthopedic diseases. Inclusion criteria for the research included age 18–75 years, BMI > 30 kg/m2, vitamin D deficiency, and no previous vitamin D supplementation. Samples were collected before and after 3 months of 4000 IU/day vitamin D supplementation. The study used enzyme-linked immunosorbent assay (ELISA) and measured serum levels of markers such as chitinase-3-like protein 1 (YKL-40), interleukin 6 (IL-6), interleukin 17 (IL-17), tumor necrosis factor (TNF-α), and adiponectin. After 3 months of vitamin D supplementation, a statistically significant increase in vitamin D and IL-17 levels was observed in the group with acute orthopedic diseases. Similarly, after supplementation, a statistically significant increase in vitamin D, IL-6 and TNF-α levels was observed in the group with chronic orthopedic diseases. Moreover, after vitamin D supplementation, statistically significantly higher adiponectin levels were observed in the chronic orthopedic group than in the acute orthopedic group. Despite high-dose vitamin D supplementation, inflammatory markers increased in acute and chronic orthopedic conditions. Based on our study, vitamin D does not reduce inflammation in patients with orthopedic conditions and obesity. Full article
(This article belongs to the Special Issue Therapeutic Use and Challenges of Vitamin D)
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17 pages, 5587 KiB  
Article
Transcriptomic Analysis Reveals the Molecular Defense Mechanisms of Poa pratensis Against Powdery Mildew Fungus Blumeria graminis f. sp. Poae
by Zhiyu Xu, Zhanchao Guo, Fan Wu, Yining Zhang, Yumin Zhao, Lingjuan Han, Peng Gao, Huisen Zhu, Qingfang Xu, Xiang Zhao and Yinping Liang
Agronomy 2024, 14(11), 2543; https://doi.org/10.3390/agronomy14112543 - 29 Oct 2024
Cited by 1 | Viewed by 1140
Abstract
Kentucky bluegrass (Poa pratensis L.) is a valuable cool-season turfgrass widely utilized for forage, turf, and ecological purposes; however, its productivity and ornamental value are significantly compromised by powdery mildew, caused by Blumeria graminis f. sp. Poae, which negatively affects turf [...] Read more.
Kentucky bluegrass (Poa pratensis L.) is a valuable cool-season turfgrass widely utilized for forage, turf, and ecological purposes; however, its productivity and ornamental value are significantly compromised by powdery mildew, caused by Blumeria graminis f. sp. Poae, which negatively affects turf quality. In the present study, we examined the interactions between P. pratensis varieties and B. graminis, focusing on primary haustorium formation at 24 h post-inoculation and the formation of germ tubes at 48 h post-inoculation. We explored the molecular mechanisms underlying the response of different P. pratensis varieties at 48 h post-inoculation via transcriptomic techniques. Our results revealed that the primary haustorium formation rate in ‘Taihang’ at 24 h after B. graminis inoculation was significantly lower than that in ‘Explorer’ and ‘Black Jack’. The conidia of B. graminis could form two to five germ tubes, and the proportion of conidia that formed five germ tubes in ‘Taihang‘ at 48 h post-inoculation was significantly lower than that in the other two varieties. Transcriptome analysis revealed 680,765 transcripts as unigenes. A total of 9983 unigenes were identified as differentially expressed genes in one or more varieties of P. pratensis after inoculation with powdery mildew compared with the control. In total, 6284 differentially expressed genes were upregulated in ‘Taihang’, which was substantially greater than those in ‘Black Jack’ (4530) and ‘Explorer’ (4666). Moreover, 2843 differentially expressed genes were specific to ‘Taihang’, whereas 1644 and 1590 unique differentially expressed genes were specific to ‘Explorer’ and ‘Black Jack’, respectively. The specifically expressed genes play crucial roles in determining the disease resistance of powdery mildew. Notably, the expression of genes encoding chitinase, gamma-glutamyltranspeptidase 1, UDP-arabinopyranose mutase 1, oxalate oxidase 2, mitogen-activated protein kinase kinase 1-like, tryptophan decarboxylase, and aromatic L-amino acid decarboxylase was closely related to powdery mildew resistance in ‘Taihang’, making them promising candidate genes for studying resistance to powdery mildew in P. pratensis. This study identified critical genes involved in powdery mildew resistance in P. pratensis, providing a basis for future gene mining and molecular breeding to increase disease resistance in P. pratensis. Full article
(This article belongs to the Special Issue Research Progress on Pathogenicity of Fungi in Crops—2nd Edition)
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21 pages, 4472 KiB  
Article
Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?
by Jakša Babel, Iva Košuta, Ana Vujaklija Brajković, Ana Lončar Vrančić, Vedran Premužić, Dunja Rogić and Nadira Duraković
J. Clin. Med. 2024, 13(19), 5991; https://doi.org/10.3390/jcm13195991 - 8 Oct 2024
Cited by 1 | Viewed by 1145
Abstract
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as [...] Read more.
Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510–0.802) and Day 3 (AUC 0.698; 95% CI: 0.559–0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572–0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice. Full article
(This article belongs to the Section Hematology)
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19 pages, 2771 KiB  
Article
The Influence of Chitosan Derivatives in Combination with Bacillus subtilis Bacteria on the Development of Systemic Resistance in Potato Plants with Viral Infection and Drought
by Liubov Yarullina, Joanna Kalatskaja, Vyacheslav Tsvetkov, Guzel Burkhanova, Ninel Yalouskaya, Katerina Rybinskaya, Evgenia Zaikina, Ekaterina Cherepanova, Kseniya Hileuskaya and Viktoryia Nikalaichuk
Plants 2024, 13(16), 2210; https://doi.org/10.3390/plants13162210 - 9 Aug 2024
Cited by 5 | Viewed by 1878
Abstract
Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including [...] Read more.
Viral diseases of potatoes are among the main problems causing deterioration in the quality of tubers and loss of yield. The growth and development of potato plants largely depend on soil moisture. Prevention strategies require comprehensive protection against pathogens and abiotic stresses, including modeling the beneficial microbiome of agroecosystems combining microorganisms and immunostimulants. Chitosan and its derivatives have great potential for use in agricultural engineering due to their ability to induce plant immune responses. The effect of chitosan conjugate with caffeic acid (ChCA) in combination with Bacillus subtilis 47 on the transcriptional activity of PR protein genes and changes in the proteome of potato plants during potato virus Y (PVY) infection and drought was studied. The mechanisms of increasing the resistance of potato plants to PVY and lack of moisture are associated with the activation of transcription of genes encoding PR proteins: the main protective protein (PR-1), chitinase (PR-3), thaumatin-like protein (PR-5), protease inhibitor (PR-6), peroxidase (PR-9), and ribonuclease (PR-10), as well as qualitative and quantitative changes in the plant proteome. The revealed activation of the expression of marker genes of systemic acquired resistance and induced systemic resistance under the influence of combined treatment with B. subtilis and chitosan conjugate indicate that, in potato plants, the formation of resistance to viral infection in drought conditions proceeds synergistically. By two-dimensional electrophoresis of S. tuberosum leaf proteins followed by MALDI-TOF analysis, 10 proteins were identified, the content and composition of which differed depending on the experiment variant. In infected plants treated with ChCA, the synthesis of proteinaceous RNase P 1 and oxygen-evolving enhancer protein 2 was enhanced in conditions of normal humidity, and 20 kDa chaperonin and TMV resistance protein N-like was enhanced in conditions of lack of moisture. The virus coat proteins were detected, which intensively accumulated in the leaves of plants infected with potato Y-virus. ChCA treatment reduced the content of these proteins in the leaves, and in plants treated with ChCA in combination with Bacillus subtilis, viral proteins were not detected at all, both in conditions of normal humidity and lack of moisture, which suggests the promising use of chitosan derivatives in combination with B. subtilis bacteria in the regulation of plant resistance. Full article
(This article belongs to the Special Issue The Role of Signaling Molecules in Plant Stress Tolerance)
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20 pages, 2013 KiB  
Article
Bioenergetic and Inflammatory Alterations in Regressed and Non-Regressed Patients with Autism Spectrum Disorder
by Maria Gevezova, Zdravko Ivanov, Iliana Pacheva, Elena Timova, Maria Kazakova, Eleonora Kovacheva, Ivan Ivanov and Victoria Sarafian
Int. J. Mol. Sci. 2024, 25(15), 8211; https://doi.org/10.3390/ijms25158211 - 27 Jul 2024
Cited by 1 | Viewed by 1926
Abstract
Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), [...] Read more.
Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved. Full article
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14 pages, 17301 KiB  
Article
CHI3L1 as a Prognostic Biomarker and Therapeutic Target in Glioma
by Jue Zhou, Dongxu Zhao, Haoyuan Tan, Jin Lan and Yinghui Bao
Int. J. Mol. Sci. 2024, 25(13), 7094; https://doi.org/10.3390/ijms25137094 - 28 Jun 2024
Cited by 2 | Viewed by 2189
Abstract
The role of Chitinase-3-like protein 1 (CHI3L1) in tumor progression has been gradually clarified in different kinds of solid tumors. Hence, we aim to elucidate its prognostic value for glioma. In this study, we analyzed RNA sequencing data combined with corresponding clinical information [...] Read more.
The role of Chitinase-3-like protein 1 (CHI3L1) in tumor progression has been gradually clarified in different kinds of solid tumors. Hence, we aim to elucidate its prognostic value for glioma. In this study, we analyzed RNA sequencing data combined with corresponding clinical information obtained from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Differentially expressed genes (DEGs) were acquired based on CHI3L1 expression profiles and were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Cox regression, least absolute shrinkage and selection operator (LASSO) regression methods, along with a nomogram, were employed to establish a predictive model. Compared with the corresponding non-tumor tissues, CHI3L1 expression was significantly upregulated in various types of solid tumors, correlating with poor clinical outcomes including glioma. GO analysis identified oxidative stress-related genes (ORGs) that were differentially expressed and modulated by CHI3L1, with 11 genes subsequently identified as potential predictors, using Univariate-Cox regression and LASSO regression. In addition, an index of oxidative stress-related genes (ORGI) was established, demonstrating its prognostic value in conjunction with CHI3L1 expression. The aberrant expression of CHI3L1 was proved in glioma patients through immunohistochemistry (IHC). Meanwhile, the knockdown of CHI3L1 inhibited glioma growth in vitro, and real-time Quantitative PCR (qPCR) confirmed decreased ORG expression upon CHI3L1 knockdown, suggesting the potential prognostic value of CHI3L1 as a therapeutic target for glioma. Full article
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22 pages, 4809 KiB  
Article
Changes in the Expression of Proteins Associated with Neurodegeneration in the Brains of Mice after Infection with Influenza A Virus with Wild Type and Truncated NS1
by Karin Donátová, Miriam Mladá, Katarína Lopušná, Filip Baran and Tatiana Betáková
Int. J. Mol. Sci. 2024, 25(5), 2460; https://doi.org/10.3390/ijms25052460 - 20 Feb 2024
Cited by 1 | Viewed by 2621
Abstract
Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, a specific link between IAV infection and neurodegenerative disease progression has been established. The non-structural NS1 protein of IAV regulates viral replication during infection and [...] Read more.
Influenza type A virus (IAV) infection is a major cause of morbidity and mortality during influenza epidemics. Recently, a specific link between IAV infection and neurodegenerative disease progression has been established. The non-structural NS1 protein of IAV regulates viral replication during infection and antagonizes host antiviral responses, contributing to influenza virulence. In the present study, we have prepared a mouse lung-to-lung adapted to the NS1-truncated virus (NS80ad). Transcriptome analysis of the gene expression in the lungs revealed that infection with wild-type A/WSN/33 (WSN), NS80, and NS80ad viruses resulted in different regulation of genes involved in signaling pathways associated with the cell proliferation, inflammatory response, and development of neurodegenerative diseases. NS1 protein did not influence the genes involved in the RIG-I-like receptor signaling pathway in the brains. Lethal infection with IAVs dysregulated expression of proteins associated with the development of neurodegenerative diseases (CX3CL1/Fractalkine, Coagulation factor III, and CD105/Endoglin, CD54/ICAM-1, insulin-like growth factor-binding protein (IGFBP)-2, IGFBP-5, IGFBP-6, chitinase 3-like 1 (CHI3L1), Myeloperoxidase (MPO), Osteopontin (OPN), cystatin C, and LDL R). Transcription of GATA3 mRNA was decreased, and expression of MPO was inhibited in the brain infected with NS80 and NS80ad viruses. In addition, the truncation of NS1 protein led to reduced expression of IGFBP-2, CHI3L1, MPO, and LDL-R proteins in the brains. Our results indicate that the influenza virus influences the expression of proteins involved in brain function, and this might occur mostly through the NS1 protein. These findings suggest that the abovementioned proteins represent a promising target for the development of potentially effective immunotherapy against neurodegeneration. Full article
(This article belongs to the Special Issue Advanced Research on Immune Response to Viral Infection)
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28 pages, 2746 KiB  
Review
Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases
by Hailong Zhao, Mingdong Huang and Longguang Jiang
Int. J. Mol. Sci. 2023, 24(22), 16149; https://doi.org/10.3390/ijms242216149 - 9 Nov 2023
Cited by 17 | Viewed by 4635
Abstract
Chitinase-3-like protein 1 (CHI3L1), a chitinase-like protein family member, is a secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic and neurological disorders, including diabetes, atherosclerosis, and Alzheimer’s disease. Aberrant CHI3L1 expression [...] Read more.
Chitinase-3-like protein 1 (CHI3L1), a chitinase-like protein family member, is a secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic and neurological disorders, including diabetes, atherosclerosis, and Alzheimer’s disease. Aberrant CHI3L1 expression is also reportedly associated with tumor migration and metastasis, as well as contributions to immune escape, playing important roles in tumor progression. However, the physiological and pathophysiological roles of CHI3L1 in the development of metabolic and neurodegenerative diseases and cancer remain unclear. Understanding the polarization relationship between CHI3L1 and macrophages is crucial for disease progression. Recent research has uncovered the complex mechanisms of CHI3L1 in different diseases, highlighting its close association with macrophage functional polarization. In this article, we review recent findings regarding the various disease types and summarize the relationship between macrophages and CHI3L1. Furthermore, this article also provides a brief overview of the various mechanisms and inhibitors employed to inhibit CHI3L1 and disrupt its interaction with receptors. These endeavors highlight the pivotal roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of metabolic diseases, neurodegenerative diseases, and cancers. Full article
(This article belongs to the Section Molecular Immunology)
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19 pages, 5574 KiB  
Article
Identification and Functional Characterization of the Nonexpressor of Pathogenesis-Related Genes 1 (NPR1) Gene in the Tea Plant (Camellia sinensis)
by Dong Jiang, Guoqun Yang, Kebin Chen, Peiyao Yu, Jiali Chen, Yong Luo, Ning Li and Li-Jun Huang
Forests 2023, 14(8), 1578; https://doi.org/10.3390/f14081578 - 2 Aug 2023
Cited by 8 | Viewed by 2470
Abstract
Tea is one of the most popular non-alcoholic beverages globally. The leaves of the tea plants serve as the raw materials for tea production, making tea tree cultivation widespread as an economically significant tree species. Nonexpressor of pathogenesis-related genes 1 (NPR1) [...] Read more.
Tea is one of the most popular non-alcoholic beverages globally. The leaves of the tea plants serve as the raw materials for tea production, making tea tree cultivation widespread as an economically significant tree species. Nonexpressor of pathogenesis-related genes 1 (NPR1) is a key regulator of the salicylic acid (SA) signaling pathway, playing a significant role in the plant’s response to biotic and abiotic stresses. However, the NPR1-like gene family in tea plants remains elusive. This study aims to systematically analyze the NPR1-like gene family in tea plants. Four CsNPR1-like genes were identified and categorized into three branches based on phylogenetic analysis. Collinearity analysis demonstrated conservation of the NPR1-like gene across different species. Analysis of cis-regulatory elements suggested that CsNPR1-like genes may be involved in various hormonal and stress responses. Protein structure analysis revealed that the CsNPR1-likes exhibited typical ANK and BTB/POZ structural domains. The protein interaction network identified various known and novel NPR1-interacting proteins, including the TGA transcription factor, which was further confirmed in planta. Meta-analysis of transcriptome data indicated that CsNPR1-like genes had spatiotemporal expression patterns and were induced by drought and cold stresses. Additionally, CsNPR1a activates the accumulation of the acidic SA-dependent pathogenic-associated protein PR1 but not the basic chitinase (PR3) in a transient expression assay. This study provides comprehensive information for investigating the NPR1-like gene family in tea plants. Full article
(This article belongs to the Special Issue Cultivation and Management in Tea Trees)
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