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16 pages, 417 KiB  
Review
Potential Biological and Genetic Links Between Dementia and Osteoporosis: A Scoping Review
by Abayomi N. Ogunwale, Paul E. Schulz, Jude K. des Bordes, Florent Elefteriou and Nahid J. Rianon
Geriatrics 2025, 10(4), 96; https://doi.org/10.3390/geriatrics10040096 - 20 Jul 2025
Viewed by 323
Abstract
Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions. Methods: Studies [...] Read more.
Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions. Methods: Studies selected (1) involved clinical research investigating genetic factors or biomarkers associated with dementia or osteoporosis, and (2) were published in English in a peer-reviewed journal between July 1993 and March 2025. We searched Medline Ovid, Embase, PsycINFO, the Cochrane Library, the Web of Science databases, Google Scholar, and the reference lists of studies following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). Results: Twenty-three studies were included in this review. These explored the role of the APOE polymorphism (n = 2) and the APOE4 allele (n = 13), associations between TREM2 mutation and late onset AD (n = 1), and associations between amyloid beta and bone remodeling (n = 1); bone-related biomarkers like DKK1, OPG, and TRAIL as predictors of cognitive change (n = 2); extracellular vesicles as bone–brain communication pathways (1); and the role of dementia-related genes (n = 1), AD-related CSF biomarkers (n = 1), and parathyroid hormone (PTH) (n = 1) in osteoporosis–dementia pathophysiology. Conclusions: Bone-related biomarkers active in the Wnt/β-Catenin pathway (Dkk1 and sclerostin) and the RANKL/RANK/OPG pathway (OPG/TRAIL ratio) present consistent evidence of involvement in AD and osteoporosis development. Reports proposing APOE4 as a causal genetic link for both osteoporosis and AD in women are not corroborated by newer observational studies. The role of Aβ toxicity in osteoporosis development is unverified in a large clinical study. Full article
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13 pages, 406 KiB  
Article
Increased Serum Sclerostin Level Is a Risk Factor for Peripheral Artery Disease in Patients with Hypertension
by Yahn-Bor Chern, Po-Sheng Lee, Ji-Hung Wang, Jen-Pi Tsai and Bang-Gee Hsu
Medicina 2025, 61(7), 1204; https://doi.org/10.3390/medicina61071204 - 1 Jul 2025
Viewed by 332
Abstract
Background and Objectives: Sclerostin and dickkopf-1 (DKK1), which are Wnt inhibitors, are involved in vascular calcification and atherosclerosis. Atherosclerotic peripheral artery disease (PAD) is highly prevalent, particularly in patients with hypertension. This study aimed to explore the association between serum concentrations of [...] Read more.
Background and Objectives: Sclerostin and dickkopf-1 (DKK1), which are Wnt inhibitors, are involved in vascular calcification and atherosclerosis. Atherosclerotic peripheral artery disease (PAD) is highly prevalent, particularly in patients with hypertension. This study aimed to explore the association between serum concentrations of Wnt pathway inhibitors and PAD in patients with hypertension. Materials and Methods: This cross-sectional trial recruited 92 patients with hypertension. PAD was defined as an ankle-brachial index < 0.9. The levels of sclerostin, DKK1, C-reactive protein (CRP), and other biochemical markers were assessed using fasting blood samples. Univariate and multivariate logistic regression and receiver operating characteristic curve analyses were conducted. Results: Patients with PAD (15.2%) had significantly higher serum sclerostin (p < 0.001) and CRP (p = 0.001) levels than those without PAD. However, the two groups did not significantly differ in terms of the DKK1 levels. Based on the multivariate analysis, sclerostin was an independent predictor of PAD (odds ratio: 1.054 per 1 pmol/L increase, 95% confidence interval: 1.019–1.090, p = 0.002) after adjusting for body mass index, fasting glucose levels, diabetes, smoking, and CRP levels. Sclerostin had a strong discriminatory power for diagnosing PAD according to the receiver operating characteristic curve analysis (area under the curve: 0.806, p < 0.001), with the best cutoff value of 71.5 pmol/L (sensitivity: 71.4%, specificity: 78.2%). Further, sclerostin was negatively associated with the ankle-brachial index, renal function, and dyslipidemia markers. Conclusions: Serum sclerostin levels are independently related to an increased risk for PAD in patients with hypertension. Therefore, it can be a potential biomarker for risk stratification and early diagnosis. Full article
(This article belongs to the Special Issue Current Advances in Cardiovascular Disease Research)
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13 pages, 4405 KiB  
Article
Meloside A Protects Dermal Papilla Cells from DHT-Induced Damage via Androgen Receptor Modulation
by Hyun Jun Park, Bong Geun Song, Ji Hoon Song, Seung Hee Park, Da Hye Wang, Ho Kyun Kwon and Ji-Ean Lee
Curr. Issues Mol. Biol. 2025, 47(6), 436; https://doi.org/10.3390/cimb47060436 - 9 Jun 2025
Viewed by 796
Abstract
Androgenetic alopecia (AGA) is associated with dihydrotestosterone (DHT)-induced apoptosis in human dermal papilla cells (HDPCs) via androgen receptor (AR) upregulation. This study aimed to evaluate the potential of Cucumis melo var. makuwa leaf extract (CLE) to attenuate these DHT-mediated effects in HDPCs. HDPCs [...] Read more.
Androgenetic alopecia (AGA) is associated with dihydrotestosterone (DHT)-induced apoptosis in human dermal papilla cells (HDPCs) via androgen receptor (AR) upregulation. This study aimed to evaluate the potential of Cucumis melo var. makuwa leaf extract (CLE) to attenuate these DHT-mediated effects in HDPCs. HDPCs were treated with CLE, and DHT-induced apoptosis and AR expression were assessed. High-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS) identified Meloside A as the principal bioactive constituent within CLE. CLE significantly attenuated DHT-induced apoptosis in HDPCs, demonstrating a 57.74% reduction at 1000 ppm. Mechanistically, Meloside A inhibited DHT-stimulated AR nuclear translocation and reduced AR protein expression. Furthermore, Meloside A decreased the expression of downstream target genes at 100 ppm, showing a 16.27% reduction in IL-6, a 26.55% reduction in TGF-β1, and a 35.38% reduction in DKK-1. Additionally, Meloside A significantly inhibited ROS generation within DHT-stimulated HDPCs by 45.45% at 100 ppm. These findings suggest that Meloside A, isolated from CLE, exerts anti-AGA effects by modulating AR nuclear translocation and gene expression. This highlights its potential as a therapeutic agent for AGA and provides a basis for developing novel therapeutic strategies for hair loss. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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14 pages, 2285 KiB  
Article
Transglutaminase 2 Stimulates Cell Proliferation and Modulates Transforming Growth Factor-Beta Signaling Pathway Independently of Epithelial–Mesenchymal Transition in Hepatocellular Carcinoma Cells
by Hiromi Yamaguchi, Ramiro José González-Duarte, Xian-Yang Qin, Yuriko Abe, Ichiro Takada, Benjamin Charroy, Verna Cázares-Ordoñez, Shigeyuki Uno, Makoto Makishima and Mariko Esumi
Int. J. Mol. Sci. 2025, 26(12), 5497; https://doi.org/10.3390/ijms26125497 - 8 Jun 2025
Viewed by 640
Abstract
Transglutaminase 2 (TG2) is a multifunctional protein and plays a role in cancer progression. We previously identified TG2 as an early-recurrence biomarker in hepatocellular carcinoma (HCC). TG2-knockdown (shTG2) and control (shCtl) HCC cell lines were used for comparative analyses to clarify the molecular [...] Read more.
Transglutaminase 2 (TG2) is a multifunctional protein and plays a role in cancer progression. We previously identified TG2 as an early-recurrence biomarker in hepatocellular carcinoma (HCC). TG2-knockdown (shTG2) and control (shCtl) HCC cell lines were used for comparative analyses to clarify the molecular mechanisms underlying the contribution of this protein to HCC malignancy. The proliferation of shTG2 cells was slightly but significantly decreased compared with that of shCtl cells. Differential gene expression profiling based on GeneChip arrays revealed the enrichment of the PI3K-Akt signaling pathway and showed that the expression of Dickkopf-1 and -3 (DKK1 and DKK3, respectively), inhibitors and modulators of the Wnt/β-catenin signaling pathway, was increased in shTG2 cells. The expression of epithelial–mesenchymal transition (EMT)-related genes was similar in both shCtl and shTG2 cells before and after TGF-β1 treatment, even though TGF-β1 markedly upregulated TG2. Thus, TG2 may contribute to cancer malignancy via the stimulation of cell proliferation signaling, such as PI3K-Akt and Wnt/β-catenin signaling, but not EMT. This effect might be further enhanced by humoral factors such as TGF-β1 from the tumor microenvironment. Full article
(This article belongs to the Special Issue Immunomodulatory Molecules in Cancer)
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17 pages, 2538 KiB  
Article
Marantodes pumilum var. alata Enhances Fracture Healing Through Gene Regulation in a Postmenopausal Rat Model
by Tijjani Rabiu Giaze, Norazlina Mohamed, Syed Alhafiz Syed Hashim, Ahmad Nazrun Shuid, Ima Nirwana Soelaiman, Norliza Muhammad, Fadhlullah Zuhair Jafar Sidik and Jamia Azdina Jamal
Pharmaceuticals 2025, 18(5), 736; https://doi.org/10.3390/ph18050736 - 16 May 2025
Viewed by 461
Abstract
Background: Marantodes pumilum var. alata (MPva) has been reported to promote fracture repair. This study investigates the role of MPva leaf extract on biochemical markers and bone-repair genes in a postmenopausal rat model to understand its fracture-healing properties. Methods: [...] Read more.
Background: Marantodes pumilum var. alata (MPva) has been reported to promote fracture repair. This study investigates the role of MPva leaf extract on biochemical markers and bone-repair genes in a postmenopausal rat model to understand its fracture-healing properties. Methods: Thirty female Sprague Dawley rats were grouped into sham-operated (Sham), ovariectomized control (OVXC), estrogen treatment (ERT), and plant treatment (MPv20 and MPv100) groups. After ovariectomy, the right tibiae of rats were fractured. The ERT group was treated with 64.5 μg/kg/day of estrogen, while the MPv20 and MPv100 groups received 20 and 100 mg/kg/day doses of MPva leaf extract, respectively, for 8 weeks. Sham and OVXC acted as untreated controls. Blood samples collected before and after treatment were assayed for pro-inflammatory cytokines (IL-6 and TNF-α), while bone samples were assayed for bone-turnover markers: osteocalcin and pyridinoline, oxidative-status markers (GPx, SOD, and MDA), and bone-repair genes (Bglap, Spp1, Dkk1, Igf1, Tnfsf11, and Fgf23). Results: IL-6, GPx, and SOD levels were significantly increased in both MPv groups (p < 0.05). IGF1 was significantly upregulated in both MPv groups, while Tnfsf11 was downregulated in the MPv20 group (p < 0.05). Conclusions: MPva leaf extract may promote bone repair by stimulating pro-inflammatory and antioxidant responses, which are associated with its regulation of Igf1 and Tnfsf11 genes. Full article
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13 pages, 974 KiB  
Article
Bone Remodeling in Children with Acute Lymphoblastic Leukemia: A Two-Year Prospective Longitudinal Study
by Paola Muggeo, Massimo Grassi, Vito D’Ascanio, Jessica Forte, Vincenzo Brescia, Francesca Di Serio, Laura Piacente, Paola Giordano, Nicola Santoro and Maria Felicia Faienza
Int. J. Mol. Sci. 2025, 26(9), 4307; https://doi.org/10.3390/ijms26094307 - 1 May 2025
Viewed by 479
Abstract
Childhood leukemia survivors are at risk of long-term complications. Data on bone remodeling in childhood acute lymphoblastic leukemia (ALL) are limited. This 2-year prospective longitudinal study investigated bone remodeling and bone turnover markers at diagnosis, during treatment, and until stopping treatment, in ALL [...] Read more.
Childhood leukemia survivors are at risk of long-term complications. Data on bone remodeling in childhood acute lymphoblastic leukemia (ALL) are limited. This 2-year prospective longitudinal study investigated bone remodeling and bone turnover markers at diagnosis, during treatment, and until stopping treatment, in ALL patients < 18 years, to clarify the influence of leukemia itself and/or chemotherapy on bone. Methods: A total of 22 ALL children (12 males, age 5.5 ± 3.6 years) underwent blood sampling at the 5 time point (T0−T4). Osteoprotegerin (OPG), receptor-activator-NF-B-ligand (RANKL), osteocalcin (OC), C-terminal-telopeptide-type-I-collagen (CTX), bone-alkaline-phosphatase (bALP), tartrate-resistant acid-phosphatase-5b (TRACP5b), procollagen-type-I-N-terminal-propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Data from patients at T0 were compared to a control group of healthy children. We used the principal component analysis (PCA) for statistics. Results: Levels of CTX, OC, P1NP, and bALP resulted lower in ALL children than controls (p = 0.009 for CTX and p < 0.001 for the others), also DKK1 and sclerostin (p < 0.0001 and p = 0.023). RANKL ed OPG were higher in patients. During T0−T4, CTX, OC, P1NP, TRACP5b, and bALP showed a significant increase, in particular at T0−T1 (end-of-induction). Less evident changes were detected onwards. Conclusions: The onset of leukemia has been revealed as a key point in determining a slowing of bone remodeling in ALL children. Full article
(This article belongs to the Special Issue Molecular Advances in Bone Metabolism and Disorders)
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11 pages, 740 KiB  
Article
Plasma Dickkopf-1 Levels Are Associated with Chronic Kidney Disease
by Yu-Hsuan Li, Yu-Cheng Cheng, Junyi Wu and I-Te Lee
Metabolites 2025, 15(5), 300; https://doi.org/10.3390/metabo15050300 - 30 Apr 2025
Viewed by 424
Abstract
Background: Wnt/β-catenin signaling is important in the development and repair of the kidney. Dickkopf-1 (DKK-1) is characterized as an inhibitor of the Wnt/β-catenin signaling pathway. Purpose: We examined the relationship between plasma DKK-1 levels and the risk of chronic kidney disease (CKD). Methods: [...] Read more.
Background: Wnt/β-catenin signaling is important in the development and repair of the kidney. Dickkopf-1 (DKK-1) is characterized as an inhibitor of the Wnt/β-catenin signaling pathway. Purpose: We examined the relationship between plasma DKK-1 levels and the risk of chronic kidney disease (CKD). Methods: In this cross-sectional study, patients without known diabetes mellitus who were admitted for coronary angiography due to angina were enrolled. Fasting blood samples were collected at a predetermined outpatient visit. Results: Among 373 enrolled patients, 62 (16.6%) were in the CKD group, and 311 (83.4%) were in the nonCKD group. Plasma DKK-1 levels were significantly higher in the CKD group than in the nonCKD group (697.2 ± 174.7 vs. 589.0 ± 193.3 pg/mL; p < 0.001). Plasma DKK-1 levels were inversely correlated with the eGFR (Pearson’s correlation coefficient = −0.265; p < 0.001). On the basis of multivariable logistic regression analyses, patients in the highest DKK-1 quartile had a significantly greater risk of CKD (OR = 4.188; 95% CI: 1.564, 11.212; p = 0.004) than did those in the lowest DKK-1 quartile. Conclusions: Plasma DKK-1 levels are associated with the risk of CKD in patients with angina. Further studies investigating the underlying mechanisms involved in the relationship between DKK-1 and CKD are warranted. Full article
(This article belongs to the Special Issue Metabolism in Kidney Disease)
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32 pages, 8767 KiB  
Article
A Multi-Agent, Laxity-Based Aggregation Strategy for Cost-Effective Electric Vehicle Charging and Local Transformer Overload Prevention
by Kristoffer Christensen, Bo Nørregaard Jørgensen and Zheng Grace Ma
Sustainability 2025, 17(9), 3847; https://doi.org/10.3390/su17093847 - 24 Apr 2025
Viewed by 611
Abstract
The rapid electrification of transportation, driven by stringent decarbonization targets and supportive policies, poses significant challenges for distribution system operators (DSOs). When numerous electric vehicles (EVs) charge concurrently, local transformers risk overloading—a problem that current tariff-based strategies do not adequately address. This paper [...] Read more.
The rapid electrification of transportation, driven by stringent decarbonization targets and supportive policies, poses significant challenges for distribution system operators (DSOs). When numerous electric vehicles (EVs) charge concurrently, local transformers risk overloading—a problem that current tariff-based strategies do not adequately address. This paper introduces an aggregator-based coordination mechanism that shifts EV charging from congested to underutilized periods using a rule-based scheduling algorithm. Unlike conventional methods that depend on complex real-time pricing signals or optimization-heavy solutions, the aggregator approach uses a simple yet effective “laxity” measure to prioritize charging flexibility. To assess technical and economic viability, a multi-agent simulation was developed to replicate residential user behavior and DSO constraints under the use of a 400 kVA low-voltage transformer. The results indicate that overloads are completely eliminated with minimal inconvenience to users, whose increased charging costs are offset by the aggregator at an annual total of under DKK 6000—significantly lower than the cost of infrastructure reinforcement. This study contributes by (i) quantifying the compensation needed to prevent large-scale overloads, (ii) presenting a replicable, computationally feasible, rule-based aggregator model for DSOs, and (iii) comparing aggregator solutions to costly transformer upgrades, underscoring the aggregator’s role as a viable tool for future distribution systems. Full article
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26 pages, 2831 KiB  
Article
Catalpol Protects Against Retinal Ischemia Through Antioxidation, Anti-Ischemia, Downregulation of β-Catenin, VEGF, and Angiopoietin-2: In Vitro and In Vivo Studies
by Howard Wen-Haur Chao, Windsor Wen-Jin Chao and Hsiao-Ming Chao
Int. J. Mol. Sci. 2025, 26(9), 4019; https://doi.org/10.3390/ijms26094019 - 24 Apr 2025
Viewed by 589
Abstract
Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study [...] Read more.
Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study aimed at investigating the protective effects and mechanisms of catalpol against oxidative stress or OGD in vitro and retinal ischemia in vivo, focusing on the modulation of key biomarkers of retinal ischemia, including HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-2, MCP-1, and the Wnt/β-catenin pathway. Cellular viability was assessed using retinal ganglion cell-5 (RGC-5) cells cultured in DMEM; a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. H2O2 (1 mM)/OGD was utilized. Vehicle or different catalpol concentrations were administered 15 min before the ischemic-like insults. The Wistar rat eyes’ intraocular pressure was increased to 120 mmHg for 60 min to induce retinal ischemia. Intravitreous injections of catalpol (0.5 or 0.25 mM), Wnt inhibitor DKK1 (1 μg/4 μL), anti-VEGF Lucentis (40 μg/4 μL), or anti-VEGF Eylea (160 μg/4 μL) were administered to the rats’ eyes 15 min before or after retinal ischemia. Electroretinogram (ERG), fluorogold retrograde labeling RGC, Western blotting, ELISA, RT-PCR, and TUNEL were utilized. In vitro, both H2O2 and OGD models significantly (p < 0.001/p < 0.001; H2O2 and OGD) induced oxidative stress/ischemic-like insults, decreasing RGC-5 cell viability (from 100% to 55.14 ± 2.19%/60.84 ± 4.57%). These injuries were insignificantly (53.85 ± 1.28% at 0.25 mM)/(63.46 ± 3.30% at 0.25 mM) and significantly (p = 0.003/p = 0.012; 64.15 ± 2.41%/77.63 ± 8.59% at 0.5 mM) altered by the pre-administration of catalpol, indicating a possible antioxidative and anti-ischemic effect of 0.5 mM catalpol. In vivo, catalpol had less effect at 0.25 mM for ERG amplitude ratio (median [Q1, Q3] 14.75% [12.64%, 20.48%]) and RGC viability (mean ± SE 63.74 ± 5.13%), whereas (p < 0.05 and p < 0.05) at 0.5 mM ERG’s ratio (35.43% [24.35%, 43.08%]) and RGC’s density (74.34 ± 5.10%) blunted the ischemia-associated significant (p < 0.05 and p < 0.01) reduction in ERG b-wave amplitude (6.89% [4.24%, 10.40%]) and RGC cell viability (45.64 ± 3.02%). Catalpol 0.5 mM also significantly protected against retinal ischemia supported by the increased amplitude ratio of ERG a-wave and oscillatory potential, along with recovering a delayed a-/b-wave response time ratio. When contrasted with DKK1 or Lucentis, catalpol exhibited similar protective effects against retinal ischemia via significantly (p < 0.05) blunting the ischemia-induced overexpression of β-catenin, VEGF, or angiopoietin-2. Moreover, ischemia-associated significant increases in apoptotic cells in the inner retina, inflammatory biomarker MCP-1, and ischemic indicator HIF-1α were significantly nullified by catalpol. Catalpol demonstrated antiapoptotic, anti-inflammatory, anti-ischemic (in vivo retinal ischemia or in vitro OGD), and antioxidative (in vitro) properties, counteracting retinal ischemia via suppressing upstream Wnt/β-catenin and inhibiting downstream HIF-1α, VEGF, and angiopoietin-2, together with its decreasing TUNEL apoptotic cell number and inflammatory MCP-1 concentration. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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21 pages, 6706 KiB  
Article
Evaluation of Efficacy of Water-Soluble Fraction of Rhus semialata Gall Extract and Penta-O-Galloyl-β-D-Glucose on Mitigation of Hair Loss: An In Vitro and Randomized Double-Blind Placebo-Controlled Clinical Study
by Hee-Sung Lee, Jae Sang Han, Ji-Hyun Park, Min-Hyeok Lee, Yu-Jin Seo, Se Yeong Jeon, Hye Ryeong Hong, Miran Kim, Seon Gil Do, Bang Yeon Hwang and Chan-Su Park
Antioxidants 2025, 14(4), 477; https://doi.org/10.3390/antiox14040477 - 16 Apr 2025
Viewed by 904
Abstract
Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose [...] Read more.
Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose (PGG), through both in vitro and clinical studies. WRGE was obtained using a standardized extraction process, and PGG was identified via HPLC-DAD and HRESIMS/MS techniques. Human dermal papilla cells (HDPCs) are specialized fibroblasts that can regulate the hair growth cycle and hair follicle growth. HDPCs are widely used in research focused on anti-hair loss. In this study, the anti-hair loss effects of WRGE and PGG on HDPCs were confirmed. WRGE and PGG enhance cell proliferation in HDPCs. These results are associated with the activation of the Wnt/β-catenin signaling pathway and the upregulation of hair growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF). Furthermore, WRGE and PGG significantly inhibited dihydrotestosterone (DHT)-mediated DKK-1 secretion and H2O2-medicated cytotoxicity. Clinical trials further validated these results, demonstrating significant improvements in hair density and visual hair appearance scores in participants treated with WRGE compared to a placebo group. These results collectively suggest that WRGE and PGG may serve as promising natural agents for the prevention and treatment of hair loss by targeting multiple biological pathways, including the regulation of hair growth factors, oxidative stress, and hormonal imbalances. Full article
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14 pages, 1568 KiB  
Article
Markers of Kidney Injury: Proenkephalin A and Uromodulin, but Not Dickkopf-3, Are Elevated in Patients After Hematopoietic Stem Cell Transplantation
by Aleksandra Kaszyńska, Małgorzata Kępska-Dzilińska, Ewa Karakulska-Prystupiuk, Agnieszka Tomaszewska, Grzegorz Władysław Basak, Marcin Żórawski, Zuzanna Jakubowska and Jolanta Małyszko
Int. J. Mol. Sci. 2025, 26(8), 3581; https://doi.org/10.3390/ijms26083581 - 10 Apr 2025
Cited by 3 | Viewed by 675
Abstract
Kidney injury encompasses a broad spectrum of structural and functional abnormalities, directly associated with stem cell transplantation. Acute kidney injury and chronic kidney disease represent perilous complications of hematopoietic stem cell transplantation (HSCT), with an elevated risk of mortality and progression to end-stage [...] Read more.
Kidney injury encompasses a broad spectrum of structural and functional abnormalities, directly associated with stem cell transplantation. Acute kidney injury and chronic kidney disease represent perilous complications of hematopoietic stem cell transplantation (HSCT), with an elevated risk of mortality and progression to end-stage renal disease. The early detection of these complications is, therefore, paramount, and research is increasingly focused on the identification of novel biomarkers of kidney damage. Recently, proenkephalin (PENK), a monomeric peptide that is freely filtered by the glomerulus and thus reflects glomerular filtration very well, has been shown to be an additional useful predictor of the occurrence of acute kidney injury and heart failure. Dickkopf-3 (DKK3) is a glycoprotein secreted by the renal tubular epithelium in response to stress and has been implicated in the development of interstitial fibrosis. It has therefore been evaluated primarily as a marker of fibrosis in chronic kidney disease (CKD), but may also help predict the development of acute kiney injury. Uromodulin is regarded as a renal marker. Previous studies have examined the potential of PENK, DKK-3 and uromodulin as a biomarker in individuals with preserved renal function. However, the urinary levels of PENK, DKK-3 and uromodulin in patients following HSCT have not yet been established. The objective of the present study was to assess urinary PENK, DKK-3, and uromodulin concentrations in patients who had been under ambulatory care of the Hematology, Transplantation and Internal Medicine Department for a minimum of three months following HSCT, and to investigate their correlations with kidney function, as reflected by serum creatinine and eGFR. The study population comprised 80 patients who had undergone allogeneic HSCT for various reasons, primarily hematological malignancies such as acute leukemias and lymphomas. In addition, 32 healthy volunteers were included in order to establish normal ranges for the biomarkers of interest. Urine concentrations of proenkephalin, DKK-3, and uromodulin were evaluated using a commercially available sandwich ELISA immunoassay. Demographic and clinical data were retrieved from the patients’ records. Statistical analyses were conducted using XLSLAT 2022 (Lumivero, Denver, CO, USA) and STATISTICAv13.0 (StatSoft, Tulsa, OH, USA). The results showed that PENK and DKK-3 levels were significantly higher in patients after HSCT compared to healthy volunteers. Furthermore, when patients were divided according to kidney function (below and over 60 mL/min/1.72 m2), it was found that the concentration of PENK and DKK-3 were significantly higher in 23 patients with CKD stage 3 relative to patients with eGFR over 60 mL min 1.72 m2. In univariate correlations, PENK demonstrated an inverse relationship with eGFR (r: −0.21, p < 0.05), while DKK-3 exhibited no significant correlation with creatinine or eGFR.Patients following allogeneic HSCT, despite having normal or near-normal kidney function, exhibited evidence of kidney injury. However, further research is necessary to ascertain the clinical utility of the novel biomarker. Full article
(This article belongs to the Special Issue Molecular Insights into Kidney Injury and Repair)
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26 pages, 2133 KiB  
Review
New Cardiovascular Risk Biomarkers in Rheumatoid Arthritis: Implications and Clinical Utility—A Narrative Review
by Anna Pamies, Joan-Carles Vallvé and Silvia Paredes
Biomedicines 2025, 13(4), 870; https://doi.org/10.3390/biomedicines13040870 - 3 Apr 2025
Viewed by 1270
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that not only causes joint inflammation but also significantly increases the risk of cardiovascular disease (CVD), leading to a higher morbidity and mortality. RA patients face an accelerated progression of atherosclerosis, attributed to both traditional [...] Read more.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that not only causes joint inflammation but also significantly increases the risk of cardiovascular disease (CVD), leading to a higher morbidity and mortality. RA patients face an accelerated progression of atherosclerosis, attributed to both traditional cardiovascular risk factors and systemic inflammation. This review focuses on emerging biomarkers for cardiovascular risk assessment in RA, aiming to enhance early detection and treatment strategies. Specifically, we examine the roles of interleukin-32 (IL-32), Dickkopf-1 (DKK-1), galectin-3 (Gal-3), catestatin (CST), and fetuin-A (Fet-A) as potential markers for CVD in this patient population. IL-32, a proinflammatory cytokine, is elevated in RA patients and plays a significant role in inflammation and endothelial dysfunction, both of which contribute to atherosclerosis. DKK-1, a Wnt signaling pathway inhibitor, has been associated with both synovial inflammation and the development of atherosclerotic plaques. Elevated DKK-1 levels have been linked to an increased CV mortality and could serve as a marker for CVD progression in RA. Gal-3 is involved in immune modulation and fibrosis, with elevated levels in RA patients correlating with disease activity and cardiovascular outcomes. Catestatin, a peptide derived from chromogranin A, has protective anti-inflammatory and antioxidative properties, though its role in RA-related CVD remains under investigation. Finally, Fet-A, a glycoprotein involved in vascular calcification, shows potential as a biomarker for CV events in RA, though data on its role remain conflicting. These biomarkers provide deeper insights into the pathophysiology of RA and its cardiovascular comorbidities. Although some biomarkers show promise in improving CV risk stratification, further large-scale studies are required to validate their clinical utility. Currently, these biomarkers are in the research phase and are not yet implemented in standard care. Identifying and incorporating these biomarkers into routine clinical practice could lead to the better management of cardiovascular risk in RA patients, thus improving outcomes in this high-risk population. This review highlights the importance of continued research to establish reliable biomarkers that can aid in both diagnosis and the development of targeted therapies for cardiovascular complications in RA. Full article
(This article belongs to the Special Issue Feature Reviews in Cardiovascular Diseases)
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16 pages, 806 KiB  
Review
Research Progress on the Influence of Novel Targeted Drugs for Osteoporosis on Glucose Metabolism
by Lingyang Meng, Lei Sun and Mei Li
Biomolecules 2025, 15(3), 331; https://doi.org/10.3390/biom15030331 - 25 Feb 2025
Cited by 1 | Viewed by 1191
Abstract
Both diabetes and osteoporosis are serious chronic conditions. Evidence is mounting that several bone-derived hormones play a role in glucose metabolism in patients with diabetes. Notably, novel biotargeted anti-osteoporotic agents have been recently found to reduce the risk of diabetes. This review explores [...] Read more.
Both diabetes and osteoporosis are serious chronic conditions. Evidence is mounting that several bone-derived hormones play a role in glucose metabolism in patients with diabetes. Notably, novel biotargeted anti-osteoporotic agents have been recently found to reduce the risk of diabetes. This review explores the correlation of osteokines, including the receptor activator of nuclear factor-κB ligand (RANKL), sclerostin, and Dickkopf-1 (DKK1) with glycemic indicators in patients with diabetes, as well as the effects of their respective monoclonal antibodies on glucose metabolism and their possible mechanisms. Denosumab, the monoclonal antibody against RANKL, has been shown to reduce glycated hemoglobin (HbA1c) and the risk of diabetes, possibly by enhancing pancreatic β-cell survival and glucagon-like peptide-1 secretion. Sclerostin was positively correlated with HbA1c and may induce insulin resistance via endoplasmic reticulum stress. The association of DKK1 with fasting plasma glucose and HbA1c is still unclear, though decreasing DKK1 levels may correlate with β-cell survival. However, few studies have investigated the effects of antibodies against sclerostin or DKK1 on glucose metabolism. Further research is required to elucidate the influence of novel anti-osteoporotic biotargeted agents on glucose homeostasis in patients with diabetes and their underlying mechanisms. Full article
(This article belongs to the Section Molecular Medicine)
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36 pages, 1941 KiB  
Review
Current Landscape of Molecular Biomarkers in Gastroesophageal Tumors and Potential Strategies for Co-Expression Patterns
by Martin Korpan, Hannah Christina Puhr, Julia M. Berger, Alexander Friedrich, Gerald W. Prager, Matthias Preusser and Aysegül Ilhan-Mutlu
Cancers 2025, 17(3), 340; https://doi.org/10.3390/cancers17030340 - 21 Jan 2025
Viewed by 2216
Abstract
The treatment of metastasized gastroesophageal adenocarcinoma largely depends on molecular profiling based on immunohistochemical procedures. Therefore, the examination of HER2, PD-L1, and dMMR/MSI is recommended by the majority of clinical practice guidelines, as positive expression leads to different treatment approaches. Data from large [...] Read more.
The treatment of metastasized gastroesophageal adenocarcinoma largely depends on molecular profiling based on immunohistochemical procedures. Therefore, the examination of HER2, PD-L1, and dMMR/MSI is recommended by the majority of clinical practice guidelines, as positive expression leads to different treatment approaches. Data from large phase-III trials and consequent approvals in various countries enable physicians to offer their patients several therapy options including immunotherapy, targeted therapy, or both combined with chemotherapy. The introduction of novel therapeutic targets such as CLDN18.2 leads to a more complex decision-making process as a significant number of patients show positive results for the co-expression of other biomarkers besides CLDN18.2. The aim of this review is to summarize the current biomarker landscape of patients with metastatic gastroesophageal tumors, its direct clinical impact on daily decision-making, and to evaluate current findings on biomarker co-expression. Furthermore, possible treatment strategies with multiple biomarker expression are discussed. Full article
(This article belongs to the Special Issue Oesogastric Cancer: Treatment and Management)
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23 pages, 18470 KiB  
Article
Single-Cell RNA Sequencing Reveals LEF1-Driven Wnt Pathway Activation as a Shared Oncogenic Program in Hepatoblastoma and Medulloblastoma
by Christophe Desterke, Yuanji Fu, Jenny Bonifacio-Mundaca, Claudia Monge, Pascal Pineau, Jorge Mata-Garrido and Raquel Francés
Curr. Oncol. 2025, 32(1), 35; https://doi.org/10.3390/curroncol32010035 - 9 Jan 2025
Cited by 3 | Viewed by 2090
Abstract
(1) Background: Hepatoblastoma and medulloblastoma are two types of pediatric tumors with embryonic origins. Both tumor types can exhibit genetic alterations that affect the β-catenin and Wnt pathways; (2) Materials and Methods: This study used bioinformatics and integrative analysis of multi-omics data at [...] Read more.
(1) Background: Hepatoblastoma and medulloblastoma are two types of pediatric tumors with embryonic origins. Both tumor types can exhibit genetic alterations that affect the β-catenin and Wnt pathways; (2) Materials and Methods: This study used bioinformatics and integrative analysis of multi-omics data at both the tumor and single-cell levels to investigate two distinct pediatric tumors: medulloblastoma and hepatoblastoma; (3) Results: The cross-transcriptome analysis revealed a commonly regulated expression signature between hepatoblastoma and medulloblastoma tumors. Among the commonly upregulated genes, the transcription factor LEF1 was significantly expressed in both tumor types. In medulloblastoma, LEF1 upregulation is associated with the WNT-subtype. The analysis of LEF1 genome binding occupancy in H1 embryonic stem cells identified 141 LEF1 proximal targets activated in WNT medulloblastoma, 13 of which are involved in Wnt pathway regulation: RNF43, LEF1, NKD1, AXIN2, DKK4, DKK1, LGR6, FGFR2, NXN, TCF7L1, STK3, YAP1, and NFATC4. The ROC curve analysis of the combined expression of these 13 WNT-related LEF1 targets yielded an area under the curve (AUC) of 1.00, indicating 100% specificity and sensitivity for predicting the WNT subtype in the PBTA medulloblastoma cohort. An expression score based on these 13 WNT-LEF1 targets accurately predicted the WNT subtype in two independent medulloblastoma transcriptome cohorts. At the single-cell level, the WNT-LEF1 expression score was exclusively positive in WNT-medulloblastoma tumor cells. This WNT-LEF1-dependent signature was also confirmed as activated in the hepatoblastoma tumor transcriptome. At the single-cell level, the WNT-LEF1 expression score was higher in tumor cells from both human hepatoblastoma samples and a hepatoblastoma patient-derived xenotransplant model; (4) Discussion: This study uncovered a shared transcriptional activation of a LEF1-dependent embryonic program, which orchestrates the regulation of the Wnt signaling pathway in tumor cells from both hepatoblastoma and medulloblastoma. Full article
(This article belongs to the Special Issue Novel Biomarkers and Liver Cancer)
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