Search Results (397)

Chronic kidney disease (CKD) is a global public health issue linked to toxic elements like cadmium (Cd) and mercury (Hg), which harm the kidneys even at low exposure levels. Copper (Cu) and zinc (Zn) imbalances could exacerbate inflammation, oxidative stress, and kidney damage because the Cu/Zn ratio could be a critical marker of renal dysfunction. The study evaluated 914 adolescents aged 11–18 through urine samples to assess the presence of kidney damage biomarkers (OPN, KIM-1, CLU, NGAL, and Cys-C) by using Luminex Magpix and trace metals (Cd, Hg, Cu, Zn) by using ICP-mass. Overweight (18.71%) and obesity (12.58%) rates were noted. Cd and Cu showed positive correlations with kidney damage biomarkers, while Zn exhibited protective effects. Regression models indicated that Cd exposure increased kidney damage markers, emphasizing the importance of Cu/Zn ratio. Environmental exposure to Cd affects kidney health even at low levels, as the Cu/Zn ratio correlates with kidney damage markers in low-Cd exposure, suggesting that the Cu/Zn ratio could participate in the nephrotoxicity process, highlighting trace element imbalance as a potential predictor of kidney function decline. Full article

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale structures. Studies indicate that topography with micro/nano features of osteoclast resorption pits causes bone marrow stromal cells (MSCs) and osteoprogenitor cells to favor differentiation into an osteoblastic phenotype. This study examined whether the biological response of human MSCs to Ti6Al4V surfaces is sensitive to laser treatment-controlled micro/nano-topography. First, 15 mm diameter Ti6Al4V discs (Spine Wave Inc., Shelton, CT, USA) were either machined (M) or additively manufactured (AM). Surface treatments included no laser treatment (NT), nanosecond laser (Ns), femtosecond laser (Fs), or nanosecond followed by femtosecond laser (Ns+Fs). Surface wettability, roughness, and surface chemistry were determined using sessile drop contact angle, laser confocal microscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Human MSCs were cultured in growth media on tissue culture polystyrene (TCPS) or test surfaces. On day 7, the levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and vascular endothelial growth factor 165 (VEGF) in the conditioned media were measured. M NT, Fs, and Ns+Fs surfaces were hydrophilic; Ns was hydrophobic. AM NT and Fs surfaces were hydrophilic; AM Ns and Ns+Fs were hydrophobic. Roughness (Sa and Sz) increased after Ns and Ns+Fs treatment for both M and AM disks. All surfaces primarily consisted of oxygen, titanium, and carbon; Fs had increased levels of aluminum for both M and AM. SEM images showed that M NT discs had a smooth surface, whereas AM surfaces appeared rough at a higher magnification. Fs surfaces had a similar morphology to their respective NT disc at low magnification, but higher magnification revealed nano-scale bumps not seen on NT surfaces. AM Fs surfaces also had regular interval ridges that were not seen on non-femto laser-ablated surfaces. Surface roughness was increased on M and AM Ns and Ns+Fs disks compared to NT and Fs disks. OCN was enhanced, and DNA was reduced on Ns and Ns+Fs, with no difference between them. OPN, OPG, and VEGF levels for laser-treated M surfaces were unchanged compared to NT, apart from an increase in OPG on Fs. MSCs grown on AM Ns and Ns+Fs surfaces had increased levels of OCN per DNA. These results indicate that MSCs cultured on AM Ns and AM Ns+Fs surfaces, which exhibited unique roughness at the microscale and nanoscale, had enhanced differentiation to an osteoblastic phenotype. The laser treatments of the surface mediated this enhancement of MSC differentiation and warrant further clinical investigation. Full article

Vital pulp therapy with calcium hydroxide or mineral trioxide aggregate (MTA) rapidly induces dystrophic calcification and promotes the accumulation of two members of small integrin-binding ligand N-linked glycoproteins: osteopontin (OPN) and dentin matrix protein-1 (DMP1). However, the precise relationship between these initial events and their roles in reparative dentinogenesis remain unclear. This study aimed to clarify the relationship between dystrophic calcification, OPN and DMP1 accumulation, and reparative dentin formation. Pulpotomy was performed on rat molars using MTA or zirconium oxide (ZrO₂). ZrO₂ was used as a control to assess pulp healing in the absence of dystrophic calcification. Pulpal responses were evaluated from 3 h to 7 days postoperatively via elemental mapping, micro-Raman spectroscopy, and histological staining. In the MTA-treated group, a calcium-rich dystrophic calcification zone containing calcite and hydroxyapatite was observed at 3 h after treatment; OPN and DMP1 accumulated under the dystrophic calcification zone by day 3; reparative dentin formed below the region of OPN and DMP1 accumulation by day 7. In contrast, these reactions did not occur in the ZrO₂-treated group. These results suggest that dystrophic calcification serves as a key trigger for OPN and DMP1 accumulation and plays a pivotal role in reparative dentinogenesis. Full article

Bone tissue regeneration is a complex process that takes place at the level of osteoblasts derived from mesenchymal cells and occurs under the action of multiple signaling pathways and through the expression of osteoregenerative markers. The leaf extract of Juglans regia L. (JR) is rich in polyphenols with demonstrated osteoregeneration effects. In the present study, we investigated the extract’s effects on three types of cells with various stages of differentiation: adult mesenchymal stem cells (MSCs), osteoblasts at low passage (O6) and osteoblasts at advanced passage (O10). To assess the efficacy of the walnut leaf extract, in vitro treatments were performed in comparison with ellagic acid (EA) and catechin (CAT). The osteoregenerative properties of the leaf extract were evaluated in terms of cell viability, bone mineralization (by staining with alizarin red) and the expression of osteogenesis markers such as osteocalcin (OC), osteopontin (OPN), dentin matrix acidic phosphoprotein 1 (DMP1) and collagen type 1A. Another compound implicated in oxidative stress response, but also a bone homeostasis regulator, nuclear factor erythroid 2-related factor 2 (NRF2), was studied by immunocytochemistry. Together with collagen amount, alkaline phosphatase (ALP) activity and NF-kB levels were measured in cell lysates and supernatants. The obtained results demonstrate that JR treatment induced osteogenic differentiation and bone mineralization, and it showed protective effects against oxidative stress. Full article

(1) Background: Multiple sclerosis (MS) is a biologically highly heterogeneous disease and has poor predictability at diagnosis. Moreover, robust data indicate that early disease activity strongly correlates with future disability. Therefore, there is a need for strong and reliable biomarkers from diagnosis to characterize and identify patients who require highly effective disease-modifying treatments (DMTs). Several biomarkers are promising, particularly neurofilament light chains (NFLs), but the relevance of others is less consolidated. (2) Methods: We evaluated a panel of axonal damage and inflammatory biomarkers in cerebrospinal fluid (CSF) and matched serum obtained from a cohort of 60 newly diagnosed MS patients. Disability at diagnosis, negative prognostic factors, and the initial DMT prescribed were carefully recorded. (3) Results: We observed correlations between different axonal biomarkers: CSF and serum NFL versus CSF total tau; and between the inflammatory marker osteopontin (OPN) and axonal biomarkers CSF p-Tau, CSF total tau, and serum NFL. CSF and serum NFL and total tau, as well as CSF OPN, positively correlated with EDSS at diagnosis. Moreover, CSF and serum NFL levels were increased in patients with gadolinium-enhancing lesions (p = 0.01 and p = 0.04, respectively) and in those treated with highly effective DMT (p = 0.049). Furthermore, CSF OPN and both CSF and serum NFL levels significantly differentiated patients based on EDSS, with a combined ROC AUC of 0.88. We calculated and internally validated biomarker (in particular serum NFL) thresholds that significantly identified patients with higher disability. Finally, CSF OPN levels and dissemination in the spinal cord were significant predictors of EDSS at diagnosis. (4) Conclusions: These preliminary exploratory data confirm the pathological interconnection between inflammation and axonal damage from early disease stages, contributing to early disability. Follow-up data, such as longitudinal disability scores, repeated serum measurements, a healthy control group, and external validation of our results, are needed. We suggest that combining several fluid biomarkers may improve the clinical characterization of patients. Full article

Background/Objectives: Increasing evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertension (HTN), a well-established cardiometabolic risk factor, both negatively impact bone metabolism. This study aimed to investigate the associations between bone turnover markers (BTMs)—namely, osteopontin (OPN) and procollagen type 1 N-terminal propeptide (P1NP)—and metabolic health indicators, non-invasive measures of liver disease severity, as well as skeletal muscle mass (SMM), muscle strength, and bone mineral density (BMD) in patients with MASLD and HTN. Methods: We enrolled 117 patients diagnosed with MASLD and HTN and conducted anthropometric measurements, laboratory analyses, abdominal ultrasound, and point shear-wave elastography. Muscle strength was evaluated using grip strength measurements and the Five Times Sit-to-Stand Test (FTSST). SMM and BMD were quantified using dual-energy X-ray absorptiometry (DEXA). Serum OPN and P1NP concentrations were quantified using enzyme-linked immunosorbent assays (ELISAs). Results: Serum OPN concentrations below 2.89 ng/mL were associated with significantly elevated levels of AST (p = 0.001), ALT (p = 0.006), and GGT (p = 0.025), while serum P1NP concentrations above 47.5 pg/mL were associated only with significantly elevated GGT levels (p = 0.024). In addition, patients with MASLD and HTN with lower serum OPN levels had higher liver stiffness values (p = 0.003). Serum OPN concentrations were inversely associated with the following metabolic health indicators: waist circumference (WC, p < 0.001) and epicardial fat thickness (EFT, p = 0.001). In addition, they were significantly elevated in patients with MASLD and HTN who had decreased spinal BMD (p = 0.017). In turn, serum P1NP levels were reduced in patients with decreased SMM (p = 0.023). Conclusions: These findings in patients with MASLD and HTN suggest an association between serum P1NP levels and SMM, and between OPN levels and spinal BMD, indicating a potential interplay among liver function, muscle mass, and bone health. Furthermore, OPN appeared to be strongly associated with overall metabolic health indicators, such as WC and EFT, whereas P1NP exhibited a stronger association with muscle mass. Full article

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory responses. It is also important in kidney stone disease, preeclampsia, cardiovascular disease, endometriosis, and cancer, among other pathological conditions. It is a crucial extracellular matrix molecule involved in oncology, due to its ability to bridge the gap between inflammation and carcinogenesis. Methods: Our systematic review has as PICO “Does Osteopontin have possible etiological and prognostic correlations in patients affected by endometrial carcinoma?” Based on online data collected from PubMed, Scholar, Embase, Scopus, and other sources, a preliminary analysis was conducted. A keyword search for “Osteopontin” AND “tumors”, “endometrial cancer”, and other related terms was used to identify the publications. The relevance of scientific research was used to select articles in English. Results: For our systematic review, the citation search yielded nine articles on the topic. At the endometrial level, OPN plays a role in a variety of biological processes, including angiogenesis, metastasis, altered tissue remodeling, immunological responses, cell adhesion, and migration. Conclusions: With established direct correlations and a potential role in the assessment of the diagnosis and prognosis of the disease, OPN participates in endometrial cancer, drawing more and more attention from researchers. Full article

A varied family of polyphenolic chemicals, flavonoids, are becoming more and more important in bone tissue engineering because of their osteogenic, anti-inflammatory, and antioxidant effects. Recent developments incorporating flavonoids into different biomaterial platforms to improve bone regeneration are emphasized in this study. Osteocalcin (OCN) expression was 2.1-fold greater in scaffolds loaded with flavonoids—such as those made of polycaprolactone (PCL)—greatly increasing human mesenchymal stem cell (hMSC) proliferation and mineralization. Comparably, a threefold increase in calcium deposition indicates increased mineralization when hydroxyapatite (HA) was functionalized with flavonoids such as quercetin. These HA scaffolds with flavonoids also showed a 45% decrease in osteoclast activity, therefore promoting balanced bone remodeling. Concurrent with flavonoids like EGCG and quercetin, chitosan-based scaffolds encouraged osteogenic differentiation with increases in osteogenic markers like osteopontin (OPN) and alkaline phosphatase (ALP) expression by up to 82%. These scaffolds also showed 82% bone defect repair after six weeks in vivo, suggesting their promise in rapid bone regeneration. With an increase of up to 32% in the bone volume-to-total volume ratio (BV/TV) and 28% greater bone–implant contact (BIC), flavonoid coatings on titanium implants enhanced osteointegration in implantology. Displaying successful osteogenesis and immunomodulation, the addition of flavonoids into metal–organic frameworks (MOFs) and injectable hydrogels demonstrated a 72% increase in new bone formation in vivo. Though further research is required to confirm long-term clinical effectiveness, these findings show the great promise of flavonoid-functionalized biomaterials in bone regeneration. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited therapeutic options. Current therapies (pirfenidone, nintedanib) exhibit modest efficacy and significant side effects, underscoring the need for novel strategies targeting early pathogenic drivers. Saroglitazar (SGZ), a dual PPARα/γ agonist with anti-inflammatory properties approved for diabetic dyslipidemia, has not been explored for IPF. We aimed to investigate SGZ’s therapeutic potential in pulmonary fibrosis and elucidate its mechanisms of action. Materials and Methods: Using a bleomycin (BLM)-induced murine pulmonary fibrosis model, we administered SGZ therapeutically. A histopathological assessment (H&E, Masson’s trichrome, collagen I immunofluorescence), Western blotting, and qRT-PCR analyzed the fibrosis progression and inflammatory markers. Flow cytometry evaluated the macrophage polarization. In vitro studies used RAW264.7 macrophages stimulated with BLM/LPS and MRC-5 fibroblast co-cultures. The NF-κB/NLRP3 pathway activation was assessed through protein and gene expression. Results: SGZ significantly attenuated BLM-induced histopathological hallmarks, including alveolar wall thickening, collagen deposition, and inflammatory infiltration. Fibrotic markers (OPN, α-SMA) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) were downregulated in the SGZ-treated mice. Mechanistically, SGZ suppressed the M1 macrophage polarization (reduced CD86⁺ populations) and inhibited the NF-κB/NLRP3 pathway activation in the alveolar macrophages. In the RAW264.7 cells, SGZ decreased the NLRP3 inflammasome components (ASC, cleaved IL-1β) and cytokine secretion. Co-cultures demonstrated that the SGZ-treated macrophage supernatants suppressed the fibroblast activation (α-SMA, collagen I) in MRC-5 cells. Conclusions: SGZ attenuates pulmonary fibrosis by suppressing macrophage-driven inflammation via NF-κB/NLRP3 inhibition and disrupting the macrophage–fibroblast crosstalk. These findings nominate SGZ as a promising candidate for preclinical optimization and future clinical evaluation in IPF. Full article

OPN is a phosphorylated glycoprotein found in all vertebrate organisms and expressed in many tissues and secretions. It is a pleiotropic protein that plays diverse roles in various pathological and physiological processes. OPN is involved in many tissue transformation events such as intestinal and brain development, the regulation of immune system activity, immune cell activation, and inflammatory responses. This protein increases the functionality of the digestive system by regulating the intestinal microbiome and may help strengthen the intestinal barrier. OPN can also influence cognitive development and behavior. In addition, its recent association with cancer has gained critical importance. The increased expression of OPN has been observed in many cancer types, which may promote tumor cell metastasis. OPN is also effective in bacterial interaction and infections; it can prevent bacterial adhesion, supporting the development of new therapeutic approaches for oral care. Furthermore, the supplementation of OPN in infant formula has positively influenced the immune and intestinal health of infants. Many recent studies have focused on these aspects. This article provides a review and comparison of the existing knowledge on the structure and functions of OPN. It emphasizes how milk-derived OPN impacts human and infant health and disease. Full article

This study aimed to investigate the effects of shear stress on osteogenic differentiation of human dental pulp stem cells (hDPSCs). The hDPSCs were subjected to shear stress for 24 h before osteogenic induction for 21 days. The mRNA expression of osteogenic markers such as RUNX2, OSX, ALP, COL1A1, OCN, and OPN was evaluated by real-time RT-PCR. Alkaline Phosphatase (ALP) activity and Alizarin Red S (ARS) staining were investigated to confirm osteogenic differentiation and mineralization of hDPSCs, respectively. The protein expression of osterix was shown by immunofluorescence staining and Western blotting. RNA sequencing was performed to investigate how shear stress affects the osteogenic differentiation of hDPSCs, which was validated through p38 inhibitor (SB203580) treatment. Real-time RT-PCR revealed that shear stress enhanced osteogenic marker-gene expression. The increased osterix protein expression was detected on Day 14 in the shear-stress loading group compared to the static group. Shear stress enhanced ALP activity and mineralization, observed on Days 14 and 21. A volcano plot exhibited up- and downregulated genes, while the p38 inhibitor markedly inhibited osteogenic differentiation of hDPSCs triggered by shear stress. In conclusion, shear stress promotes the osteogenic differentiation of hDPSCs through the p38 mitogen-activated protein kinase signaling pathway. Full article

Osteopontin (OPN) is a protein that plays many essential functions in the human body. It is present in most tissues and body fluids. OPN, among other things, participates in wound healing, the formation and remodeling of bone, immune response, inflammation, angiogenesis, and tumor formation. A new analytical method, based on SPRi (surface plasmon resonance imaging) biosensors, has been developed to determine osteopontin in biological fluids. OPN was captured from a solution by an immobilized antibody (mouse or rabbit), a bioreceptor in the SPRi sensor. A separate validation process was carried out for each antibody used. The LOD and LOQ values obtained for the biosensor with mouse antibody were 0.014 ng mL⁻¹ and 0.043 ng mL⁻¹, respectively, and those obtained for the biosensor with rabbit antibody were 0.018 ng mL⁻¹ and 0.055 ng mL⁻¹, respectively. The response ranges of both biosensors were in a similar range: 0.05–1.00 ng mL⁻¹. OPN was determined in blood plasma to demonstrate the sensor potential, showing good agreement with the data obtained using an ELISA test and reported in the literature. The presented method is characterized by ease and speed of measurement, and the process does not require special preparation of samples. Full article

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. In most cases, higher SPP1 levels in serum, bronchoalveolar lavage fluid, or lung tissue carry a poor prognosis. SPP1 is expressed in multiple cells critical for fibrogenesis, including macrophages, epithelial cells, and fibroblasts, and SPP1 has emerged as a potential target for therapeutic interventions. Here, we review the proposed mechanisms by which SPP1 contributes to the development of lung disease, with an emphasis on ILD. Full article

Background: Myeloid-derived suppressor cells (MDSCs) contribute to immune suppression observed in chronic lymphocytic leukemia (CLL). MDSCs are immature myeloid cells that are hijacked during development and further reprogrammed by the tumor microenvironment (TME) to harbor immune-suppressive properties and inhibit T-cell functions. Bromodomain and extraterminal domain (BET) proteins, including BRD4, are epigenetic modulators that regulate genes implicated in CLL pathogenesis and TME interactions. Previously, we investigated how the novel BET inhibitor OPN-51107 (OPN5) prevents CLL disease expansion, modulates T-cell immune function, and alters gene expression related to MDSCs. In turn, we hypothesize that BET proteins such as BRD4 regulate MDSC functions, and subsequent pharmacological inhibition of BRD4 will alleviate MDSC-mediated immune suppression in CLL. Methods: Utilizing the Eµ-TCL1 mouse model of CLL, we evaluated BRD4 protein expression in MDSCs derived from the bone marrow of transgenic and age-matched wild-type (WT) mice. We then investigated the ex vivo functionality of OPN5-treated MDSCs, expanded from Eµ-TCL1 and WT bone marrow in MDSC-supportive medium. Finally, we conducted an in vivo study utilizing the Eµ-TCL1 adoptive transfer mouse model to determine the in vivo effects of OPN5 on MDSCs and other immune populations. Results: Through the course of this study, we found that MDSCs isolated from Eμ-TCL1 mice upregulate BRD4 expression and are more immune-suppressive than their WT counterparts. Furthermore, we demonstrated ex vivo OPN5 treatment reverses the immune-suppressive capacity of MDSCs isolated from leukemic mice, evident via enhanced T-cell proliferation and IFNγ production. Finally, we showed in vivo OPN5 treatment slows CLL disease progression and modulates immune cell populations, including MDSCs. Conclusions: Altogether, these data support BET inhibition as a useful therapeutic approach to reverse MDSC-mediated immune suppression in CLL. Full article