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Background: Osteopontin (OPN) is a glycoprotein involved in various physiological and pathological processes, and its aberrant expression in cancer cells is closely linked to tumor progression. In colorectal cancer (CRC), OPN is overexpressed, but the roles of its splice variants (OPN-SVs), OPNa, OPNb, and OPNc, are not well understood. This study aimed to characterize the expression patterns of OPN-SVs and their potential diagnostic and prognostic implications in CRC using transcriptomic data deposited in TSVdb and TCGA. Methods: The expression patterns of each OPN-SV were analyzed using transcriptomic data deposited in TSVdb and TCGA, which were correlated to patient data available at cBioPortal. Results: Bioinformatic analysis revealed that OPNa, OPNb, and OPNc are overexpressed in CRC samples compared to non-tumor samples. Notably, OPNa and OPNc are overexpressed in CRC stages (II, III, and IV) compared to stage I. Higher levels of OPNa and OPNc transcripts are associated with worse overall survival (OS) and shorter progression-free survival (PFS) in CRC patients. Additionally, the expression of OPNa, OPNb, and OPNc is correlated with BRAFV600E mutations in CRC samples. Conclusions: These findings suggest that OPNa and OPNc, in particular, have potential as diagnostic and prognostic biomarkers, paving the way for their further evaluation in CRC diagnosis and prognosis.

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections.

Natural components of breast milk, human milk oligosaccharides (HMOs) and osteopontin (OPN) have been shown to have a variety of functional activities and are widely used in infant formulas. However, the preventive and therapeutic effects of both on influenza viruses are not known. In this study, antiviral assays using a human laryngeal carcinoma cell line (HEP-2) showed that 3'-sialyllactose (3'-SL) and OPN had the best antiviral ability with IC50 values of 33.46 mMand 1.65 mM, respectively. 3'-SL (10 mM) and OPN (4 mM) were used in combination to achieve 75% inhibition. Further studies found that the combination of 200 mg/mL of 3'-SL with 500 mg/mL of OPN exerted the best antiviral ability. The reason for this was related to reduced levels of the cytokines TNF-a, IL-6, and iNOS in relation to mRNA expression. Plaque assay and TCID50 assay found the same results and verified synergistic effects. Our research indicates that a combination of 3'-SL and OPN can effectively reduce inflammatory storms and exhibit antiinfluenza virus effects through synergistic action. [ABSTRACT FROM AUTHOR]

Background: Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods: We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results: In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (− 33% per year; 95% confidence interval [− 54, − 3.7]), but not OPN or VEGF-A (− 0.3% or − 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions: We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic systemic disease with an immunological basis and a complex pathophysiology. The chronic inflammatory status of psoriasis is associated with several comorbidities, such as metabolic syndrome, obesity, and cardiovascular disease. The development of psoriasis is influenced by osteopontin, a glycoprotein that influences physiological and pathological reactions by modulating Th1 and Th17 cellular responses, stimulating keratinocyte proliferation, regulating cellular apoptosis, and promoting angiogenesis. The recent identification of immune pathways involved in psoriasis development has facilitated the development of biological treatments; however, a better understanding of the intricate relationship between underlying inflammatory processes, psoriasis development, and accompanying comorbidities is needed for improved disease management. [ABSTRACT FROM AUTHOR]

Purpose: Obesity is a risk factor and poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC), but the underlying mechanisms remain unclear. Methods: PDAC cells and obese visceral adipocytes (O-Ad) derived from mice and humans were used to analyze interactions between the two cell types, and human microvascular endothelial cells were used for angiogenesis assay. A xenograft mouse model with subcutaneously injected PDAC cells was used for animal studies. The relationship between visceral fat and prognosis was analyzed using resected tissues from PDAC patients with and without obesity. Results: Conditioned media (CM) from O-Ad significantly increased PDAC cell growth and migration and angiogenic capacity in both human and mice cells, and blocking osteopontin (OPN) in O-Ad canceled O-Ad-induced effects in both mouse and human cells. In addition, O-Ad directly increased the migratory and tube-forming capacities of endothelial cells, while blocking OPN canceled these effects. O-Ad increased AKT phosphorylation and VEGFA expression in both PDAC and endothelial cells, and OPN inhibition in O-Ad canceled those O-Ad-induced effects. In the xenograft model, PDAC tumor volume was significantly increased in obese mice compared with lean mice, whereas blocking OPN significantly inhibited obesity-accelerated tumor growth. OPN expression in adipose tissues adjacent to human PDAC tumor was significantly higher in obese patients than in non-obese patients. In PDAC patients with obesity, high OPN expression in adipose tissues was significantly associated with poor prognosis. Conclusion: Obese adipocytes trigger aggressive transformation in PDAC cells to induce PDAC progression and accelerate angiogenesis via OPN secretion. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is characterized by an immunosuppressive tumor microenvironment (TME) strictly associated with therapy resistance. Cyclooxygenase-2 (COX-2) fuels GBM proliferation, stemness, and chemoresistance. We previously reported that COX-2 upregulation induced by temozolomide (TMZ) supported chemoresistance. Also, COX-2 transfer by extracellular vesicles released by T98G promoted M2 polarization in macrophages, whereas COX-2 inhibition counteracted these effects. Here, we investigated the COX-2 role in the stemness potential and modulation of the GBM immunosuppressive microenvironment. The presence of macrophages U937 within tumorspheres derived from GBM cell lines and primary cultures exposed to celecoxib (COX-2 inhibitor) with or without TMZ was studied by confocal microscopy. M2 polarization was analyzed by TGFβ-1 and CD206 levels. Osteopontin (OPN), a crucial player within the TME by driving the macrophages' infiltration, and CD44 expression was assessed by Western blot. TMZ strongly enhanced tumorsphere size and induced the M2 polarization of infiltrating macrophages. In macrophage-infiltrated tumorspheres, TMZ upregulated OPN and CD44 expression. These TMZ effects were counteracted by the concurrent addition of CXB. Remarkably, exogenous prostaglandin-E2 restored OPN and CD44, highlighting the COX-2 pivotal role in the protumor macrophages' state promotion. COX-2 inhibition interfered with TMZ's ability to induce M2-polarization and counteracted the development of an immunosuppressive TME. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases. [ABSTRACT FROM AUTHOR]

Primary hepatic carcinoma (PHC) is a leading threat to cancer patients with few effective treatment strategies. OPN is found to be an oncogene in hepatocellular carcinoma (HCC) with potential as a treating target for PHC. Fenofibrate is a lipid-lowering drug with potential anti-tumor properties, which is claimed with suppressive effects on OPN expression. Our study proposes to explore the molecular mechanism of fenofibrate in inhibiting HCC. OPN was found extremely upregulated in 6 HCC cell lines, especially Hep3B cells. Hep3B and Huh7 cells were treated with 75 and 100 μM fenofibrate, while OPN-overexpressed Hep3B cells were treated with 100 μM fenofibrate. Decreased clone number, elevated apoptotic rate, reduced number of migrated cells, and shortened migration distance were observed in fenofibrate-treated Hep3B and Huh7 cells, which were markedly abolished by the overexpression of OPN. Furthermore, the facilitating effect against apoptosis and the inhibitory effect against migration of fenofibrate in Hep3B cells were abolished by 740 Y-P, an agonist of PI3K. Hep3B xenograft model was established, followed by treated with 100 mg/kg and 200 mg/kg fenofibrate, while OPN-overexpressed Hep3B xenograft was treated with 200 mg/kg fenofibrate. The tumor growth was repressed by fenofibrate, which was notably abolished by OPN overexpression. Furthermore, the inhibitory effect of fenofibrate on the PI3K/AKT/Twist pathway in Hep3B cells and Hep3B xenograft model was abrogated by OPN overexpression. Collectively, fenofibrate suppressed progression of hepatoma downregulating OPN through inhibiting the PI3K/AKT/Twist pathway. [ABSTRACT FROM AUTHOR]

Background: Mid-Palatal suture expansion needs long retention period due to delayed bone formation in the expanded suture. Platelet-rich plasma (PRP) is a concentrated source of growth factors which increase bone formation. The aim of this study was to evaluate the effect of PRP injection on bone formation in expanded mid palatal suture in rabbits. Methods: In this prospective randomized controlled animal study, Twenty male rabbits (8-weeks-old) were subjected to mid-palatal expansion for 5 days. Animals were afterwards randomly divided into control group A & study group B. PRP was prepared and injected in the mid-palatal suture in animals belonging to group B only. After 6 weeks of retention, all animals were euthanized, and premaxillae were prepared for histological, histomorphometric and immunohistochemical analysis. Student t-test and paired t-test were used to compare the means of the two groups and within the same group respectively. Significance level set at p ≤ 0.05. Results: Histomorphometric analysis revealed a significant increase (p < 0.001) in the mean percentage of new bone in the study group (14.4%) compared to the control (1.4%). Suture width in study group was significantly wider than the control group (278.8 ± 9μms and 120.4 ± 3.4μms, p < 0.001). There was a significant increase in vascular density in study group than control group (309 ± 65.34 and 243.86 ± 48.1, p = 0.021). Osteopontin immuno-expression revealed a significant increase in optical density in study group than control group (0.21 ± 0.02 & 0.12 ± 0.01, p < 0.001). Conclusions: In rabbit model, PRP injection can accelerate new bone formation in the expanded mid-palatal suture when compared to the control. This could hopefully result in a more stable midpalatal expansion and a reduced retention period. [ABSTRACT FROM AUTHOR]

COVID-19 survivors commonly report persistent symptoms. In this observational study, we investigated the link between osteopontin (OPN) and post-acute COVID-19 symptoms and lung functional/imaging abnormalities. We recorded symptoms and lung imaging/functional data from previously hospitalized COVID-19 patients, who were followed for 4–84 weeks (122 patients/181 visits) post-symptom onset at our outpatient clinic. Circulating OPN was determined using ELISA. Plasma OPN levels were higher in symptomatic patients (compared with the asymptomatic ones); those with dyspnea (compared with those without dyspnea);those with a combination of serious symptoms, i.e., the presence of at least one of the following: dyspnea, fatigue and muscular weakness (compared with those with none of these symptoms); and those with dyspnea and m-MRC > 1 (compared with those with m-MRC = 0–1). Plasma OPN levels were inversely correlated with EQ-VAS (visual analog scale of the EQ-5D-5L health-related quality-of-life questionnaire) values. High-resolution CT or diffusion lung capacity (DLCO) findings were not related to circulating OPN. In the multiple logistic regression, the presence of symptoms, dyspnea, or the combination of serious symptoms were linked to female gender, increased BMI and pre-existing dyspnea (before the acute disease), while increased plasma OPN levels, female gender and pre-existing dyspnea with m-MRC > 1 were independently associated with severe post-COVID-19 dyspnea (m-MRC > 1). Using a correlation matrix to investigate multiple correlations between EQ-VAS, OPN and epidemiological data, we observed an inverse correlation between the OPN and EQ-VAS values. Increased circulating OPN was linked to the persistence of severe exertional dyspnea and impaired quality of life in previously hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

Secreted phosphoprotein 1 [SPP-1, also known as osteopontin (OPN)] is a secretory protein and glycosylation phosphoprotein. SPP-1 is involved in a variety of biological functions in the physiological and pathological processes with the ability to exert the process of bone formation, modulate the inflammatory and immune responses, regulate tumor growth and metastasis. Recently, correlational studies indicate that SPP-1 plays a crucial role in the development and progression of pulmonary diseases. In this study, the association of SPP-1 with pulmonary diseases was reviewed to further improve and deepen the awareness of the pathogenesis and therapy of pulmonary diseases. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31–5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26–3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a multifunctional protein that plays a pivotal role in the immune system. It is involved in various biological processes, including cell adhesion, migration and survival. The study of the immunomodulatory effects of OPN is of paramount importance due to its potential therapeutic applications. A comprehensive understanding of how OPN regulates the immune response could pave the way for the development of novel treatments for a multitude of diseases, including autoimmune disorders, infectious diseases and cancer. Therefore, in the following paper, we provide a systematic overview of OPN and its immunoregulatory roles in various diseases, laying the foundation for the development of OPN-based therapies in the future. [ABSTRACT FROM AUTHOR]

Recently, we demonstrated that the corpora amylacea (CA), a glycoprotein-rich aggregate frequently found in aged brains, accumulates in the ischemic hippocampus and that osteopontin (OPN) mediates the entire process of CA formation. Therefore, this study aimed to elucidate the mechanisms by which astrocytes and microglia participate in CA formation during the late phase (4-12 weeks) of brain ischemia. Based on various morphological analyses, including immunohistochemistry, in situ hybridization, immunoelectron microscopy, and correlative light and electron microscopy, we propose that astrocytes are the primary cells responsible for CA formation after ischemia. During the subacute phase after ischemia, astrocytes, rather than microglia, express Opn messenger ribonucleic acid and OPN protein, a surrogate marker and key component of CA. Furthermore, the specific localization of OPN in the Golgi complex suggests that it is synthesized and secreted by astrocytes. Astrocytes were in close proximity to type I OPN deposits, which accumulated in the mitochondria of degenerating neurons before fully forming the CA (type III OPN deposits). Throughout CA formation, astrocytes remained closely attached to OPN deposits, with their processes exhibiting well-developed gap junctions. Astrocytic cytoplasmic protein S100b, a calcium-binding protein, was detected within the fully formed CA. Additionally, ultrastructural analysis revealed direct contact between astroglial fibrils and the forming facets of the CA. Overall, we demonstrated that astrocytes play a central role inmediating CA formation fromthe initial stages of OPN deposit accumulation to the evolution of fully formed CA following transient ischemia in the hippocampus. [ABSTRACT FROM AUTHOR]

The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes , whereas it decreased Proteobacteria , Helicobacteraceae , and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis. [ABSTRACT FROM AUTHOR]

In osteoarthritis, a joint disease there is progressive loss if articular cartilage that leads to loss of function and chronic pain in affected joints. Clinically presents as pain, stiffness,decreased mobility,crepitus and deformity of joints. The patients with osteoarthritis exhibit a higher level of osteopontin (OPN) in serum,plasma and synovial fluids.A systemic review revealed that the OPN levels were markedly increased in plasma, serum and synovial fluids of patients with osteoarthritis. Therefore,OPN levels are directly related to advancements in joint damage as well as progression of disease .OPN is a matrix glycoprotein that is expressed in response to tissue trauma .It in turns increase the activity of nuclear factor kabba B and other inflammatory mediators and enhance the inflammatory cascade.Reduction in levels if OPN halts the apoptosis if chondrocytes and angiogenesis .It can also be used as a biomarker in grading the progression and severity of osteoarthritis. Radiography are gold standard investigations but on radiography, the damage is visualized after a long time in terms if loss of joint space. Biomarkers are used now for diagnostic and prognostic purposes. A study revealed that OPN levels are also increased in idiopathic hip Osteoarthritis so it can be used as a biochemical marker for diagnosing and determining the severity of disease. Biomarkers like OPN helps diagnosing the disease in early stages leading to earlier intervention. However,further studies are still needed to to establish a strong connection. [ABSTRACT FROM AUTHOR]

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is located on chromosome 4q22.1. This multifunctional secreted acidic glycoprotein is expressed intracellularly and extracellularly in various tissues, where it interacts with regulatory proteins and pro-inflammatory immune chemokines, contributing to the pathogenesis of multiple diseases. Nevertheless, the intricate genetic connections between SPP1 and ovarian aging remain largely unexplored. This study aims to bridge this knowledge gap by delving into ovarian aging and its associations with SPP1 using multi-omics data analysis. Our findings indicate that SPP1 is a potential gene related to ovarian aging. To comprehend the role of SPP1, we conducted spatial transcriptomic analyses on young and aged female mouse ovaries, revealing a significant decline in SPP1 expression in the aging group compared to the young group. Similarly, a significantly low level of SPP1 was found in the 73-year-old sample. Additionally, in-depth single-cell RNA-sequencing analysis identified associations between SPP1 and ITGAV, ITGB1, CD44, MMP3, and FN1. Notably, co-expression analysis highlighted a strong correlation between SPP1 and ITGB1. In summary, this study pioneers the identification of SPP1 as a gene implicated in ovarian aging. Further research into the role of SPP1 has the potential to advance precision medicine and improve treatment strategies for ovarian aging-related conditions. [ABSTRACT FROM AUTHOR]

The early detection of melanoma relapse can improve patient survival; thus, there is a great need for easily accessible biomarkers that facilitate the diagnosis of metastatic disease. We investigated the diagnostic effect of blood biomarkers such as lactate dehydrogenase (LDH), S100B, and osteopontin in the detection of metastases. Clinical data and peripheral blood samples of 206 melanoma patients were collected (no metastasis, N = 120; metastasis, N = 86). The discriminative power of blood biomarkers, patient demographics, and clinicopathological parameters of primary melanomas were evaluated using univariate and multivariate logistic regression models and receiver operating characteristic (ROC) analysis to determine the area under the curve (AUC). Plasma osteopontin levels showed a significant and independent effect on the probability of metastasis, similar to serum S100B levels. In addition, the location of the primary tumor on the lower extremities and the American Joint Committee on Cancer (AJCC) categories pT2b-3a, pT3b-4a, and pT4b were associated with the diagnosis of metastasis. Importantly, the combination of the three blood biomarkers and primary tumor localization and AJCC pT category yielded excellent discrimination (AUC: training set: 0.803; validation set: 0.822). In conclusion, plasma osteopontin can be classified as a melanoma biomarker; moreover, by combining clinicopathological prognostic variables, the diagnostic effect of blood biomarkers in the detection of metastatic melanoma can be improved. [ABSTRACT FROM AUTHOR]

Analysis of skin development in the Australian lungfish, Neoceratodus forsteri, indicates that keratinocytes form 2 to 3 irregular layers in tadpoles of 2–5 cm in length and are fully stratified (7–12 layers) in juveniles of 16.5–26 cm in length. The epidermis produces mucus and mainly contains intermediate filament keratins of acidic nature but also a minute amount of neutral‐basic keratins (pI 7.0–7.3), which is unique among fish. The latter keratins of 60–62 kDa, are generally present in tetrapods but the specific gene structure and amino sequence of acidic, neutral and basic keratins in N. forsteri are presently unknown. No other epidermal proteins are detected although biochemical data suggest the presence of non‐keratin proteins, including a basic type (pI 8.0–8.2) of around 32 kDa of molecular weight. The spinulated bony layer of elasmoid scales contains glycoproteins involved in mineralization, such as osteonectin and osteopontin. Also, alkaline phosphatase, involved in calcium precipitation onto the collagen matrix, has been detected in scales of juveniles up to 26 cm in length. The present review concludes that the knowledge of the data derived from epidermal and dermal protein annotation from the recently sequenced genome of this fish species will contribute to address the study on the evolution of tetrapod skin. [ABSTRACT FROM AUTHOR]

The development of the metanephros in one‐humped camels involves a complex series of interactions between epithelial and mesenchymal cells. As a result, there is a synchronized differentiation process of stromal, vascular and epithelial cell types during glomerulogenesis, angiogenesis and tubulogenesis. In the current work, the metanephros of camel foetuses were divided into four stages where kidneys from each stage were processed and immunoassayed, followed by quantitative analysis to determine target protein intensities throughout metanephrogenesis in the camel. This study demonstrated robust expression of α‐smooth muscle actin (α‐SMA) in the glomerular mesangium, as well as in interlobular and glomerular arterioles during the earlier stages of development. However, in the late stages, α‐SMA expression became more localized around the blood capillaries in both the cortex and medulla. Strong expression of CD34 was observed in the immature glomerular and peritubular endothelial cells within the subcapsular zone, as well as in the glomerular, proximal tubular and distal tubular epithelium of stage one foetuses, although its expression gradually diminished with foetal maturation. The expression pattern of osteopontin was prominently observed in the distal convoluted tubules throughout all stages, however, no expression was detected in the proximal tubules, glomeruli and arterioles. E‐cadherin was detected in the developing renal tubular epithelial cells but not in the glomeruli. In conclusion, this study reveals the spatiotemporal distribution of key proteins, including α‐SMA, CD34, Osteopontin and E‐cadherin, which play a crucial role in metanephrogenesis in camel foetuses. [ABSTRACT FROM AUTHOR]

Background: Renal ischemia/reperfusion is an imperative cause of acute kidney damage which in turn releases detrimental mediators into the circulation leading to subsequent remote organ injury. Aim of the study: to assess the possible protective effects of diacerein (DIA), an interleukin-1 receptor antagonist, against renal ischemia/reperfusion (I/R) induced kidney and lung injuries in male albino. Material, Methods: Rats were randomly assigned into: sham, I/R, and DIA-pretreated I/R groups. DIA was orally administered in doses of 25, 50 and 100 mg/kg/day for 20 days, then, both right and left renal pedicles were clamped for 45 min followed by reperfusion for 24 h. One-way ANOVA followed by Post-Hoc test were used to compare the results. PValue of <0.05 was considered as statistically significant. Results: DIA significantly reduced serum creatinine and blood urea nitrogen (BUN), improved both kidney and lung histoarchitecture, reduced pulmonary interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-a), osteopontin (OPN), elevated superoxide dismutase(SOD), glutathione (GSH), nuclear factor erythroid 2-related factor 2 (Nrf-2), Heme oxygenase 1 (HO-1), and reduced malondialdehyde (MDA) lung levels. Conclusion: Our results show that DIA has a promising protective impact against kidney and lung injuries prompted by renal I/R. This effect is proposed to be mediated, partially, by downregulation of osteopontin and upregulation of Nrf-2/HO-1. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a secreted integrin‐binding protein that plays a role in inflammation, cellular viability, cell adhesion and migration, cancer development, and diabetes through different mechanisms. The splice variants of OPN can play essential roles in cancer development, progression, and metastasis formation; however, limited data are available about the role of OPN isoforms in human malignant melanoma. Our goal was to define the gene expression patterns of five OPN variants (OPN4, OPN5, OPNa, OPNb, and OPNc), integrin, and CD44 receptor genes in primary and metastatic melanoma‐originated cell lines (n = 19), and to explore the association of the expression patterns with clinicopathological parameters. We evaluated the invasive property of the cell lines and investigated the potential association between the invasion and gene expression of OPN isoforms. We found a significant rise in the expression of OPNc in the invasive cell lines compared to the noninvasive cells and detected significantly higher expression of the OPN splice variants in melanoma cell lines originating from more advanced stages tumors than cell lines originating from early‐stage melanomas. The correlation analysis revealed that all five OPN variants positively correlated with ITGB3 and ITGA9, whereas OPN5 positively correlated with ITGB1, ITGAV, ITGA6, and CD44. OPN can activate extracellular signal‐regulated kinase signaling through binding to α9β1 integrin, promoting melanoma tumor cell migration. It is possible that such associations between OPN splice variants and integrin receptors may play a role in melanoma progression. In conclusion, our findings suggest that high expression of OPNc correlates with the invasive behavior of melanoma cells. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The secreted phosphoprotein 1 (SPP1) gene expressed by CD11c+ cells is known to be associated with microglia activation and neuroinflammatory diseases. As most studies rely on mouse models, we investigated these genes and proteins in the cortical brain tissue of older adults and their role in Alzheimer's disease (AD) and related disorders. METHODS: We leveraged protein measurements, single‐nuclei, and RNASeq data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) of over 1200 samples for association analysis. RESULTS: Expression of SPP1 and its encoded protein osteopontin were associated with faster cognitive decline and greater odds of common neuropathologies. At single‐cell resolution, integrin subunit alpha X (ITGAX) was highly expressed in microglia, where specific subpopulations were associated with AD and cerebral amyloid angiopathy. DISCUSSION: The study provides evidence of SPP1 and ITGAX association with cognitive decline and common neuropathologies identifying a microglial subset associated with disease. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to investigate the potential role of tissue osteopontin, also known as secreted phosphoprotein 1 (SPP1), as a contributing factor to an unfavorable prognosis in classical Hodgkin's lymphoma (HL) patients who received the same treatment protocol. The study involved 44 patients aged 4–22 years, with a median follow-up period of 3 years. Patients with higher levels of SPP1 were associated with tissue necrosis and inflammation, and there was a trend toward a poorer prognosis in this group. Before therapy, we found a correlation between positron emission tomography (PET) scans and logarithmic SPP1 levels (p = 0.035). However, the addition of SPP1 levels did not significantly enhance the predictive capacity of PET scans for recurrence or progression. Elevated SPP levels were associated with tissue mRNA counts of chemotactic and inflammatory chemokines, as well as specific monocyte/dendritic cell subtypes, defined by IL-17RB, PLAUR, CXCL8, CD1A, CCL13, TREM1, and CCL24 markers. These findings contribute to a better understanding of the potential factors influencing the prognosis of HL patients and the potential role of SPP1 in the disease. While the predictive accuracy of PET scans did not substantially improve during the study, the results underscore the complexity of HL and highlight the relationships between SPP1 and other factors in the context of HL relapse. [ABSTRACT FROM AUTHOR]

Background: Antibody-mediated complement fixation has previously been associated with protection against malaria in naturally acquired immunity. However, the process of early-life development of complement-fixing antibodies in infants, both in comparison to their respective mothers and to other immune parameters, remains less clear. Results: We measured complement-fixing antibodies in newborns and their mothers in a malaria endemic area over 5 years follow-up and found that infants’ complement-fixing antibody levels were highest at birth, decreased until six months, then increased progressively until they were similar to birth at five years. Infants with high levels at birth experienced a faster decay of complement-fixing antibodies but showed similar levels to the low response group of newborns thereafter. No difference was observed in antibody levels between infant cord blood and mothers at delivery. The same result was found when categorized into high and low response groups, indicating placental transfer of antibodies. Complement-fixing antibodies were positively correlated with total schizont-specific IgG and IgM levels in mothers and infants at several time points. At nine months, complement-fixing antibodies were negatively correlated with total B cell frequency and osteopontin concentrations in the infants, while positively correlated with atypical memory B cells and P. falciparum-positive atypical memory B cells. Conclusion: This study indicates that complement-fixing antibodies against P. falciparum merozoites are produced in the mothers and placentally-transferred, and they are acquired in infants over time during the first years of life. Understanding early life immune responses is crucial for developing a functional, long lasting malaria vaccine. [ABSTRACT FROM AUTHOR]

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the c.495C > T polymorphism within exon 1 of the osteopontin gene (OPN), and to analyze its association with susceptibility to ketosis in Polish Holstein–Friesian (HF) cows. The study utilized blood samples from 977 HF cows, for the determination of β-hydroxybutyric acid (BHB) and for DNA isolation. The c.495C > T polymorphism of the bovine osteopontin gene was determined by PCR–RFLP. The CT genotype (0.50) was deemed the most common, while TT (0.08) was the rarest genotype. Cows with ketosis most often had the CC genotype, while cows with the TT genotype had the lowest incidence of ketosis. To confirm the relationship between the genotype and ketosis in cows, a weight of evidence (WoE) was generated. A very strong effect of the TT genotype on resistance to ketosis was demonstrated. The distribution of the ROC curve shows that the probability of resistance to ketosis is > 75% if cows have the TT genotype of the OPN gene (cutoff value is 0.758). Results suggest that TT genotype at the c.495C > T locus of the OPN gene might be effective way to detect the cows with risk of ketosis. [ABSTRACT FROM AUTHOR]

Background and aims: Inducible T-cell Co-Stimulator (ICOS) present on T-lymphocytes and its ligand ICOSL expressed by myeloid cells play multiple roles in regulating T-cell functions. However, recent evidence indicates that reverse signalling involving ICOSL is also important in directing the differentiation of monocyte-derived cells. In this study, we investigated the involvement of ICOS/ICOSL dyad in modulating macrophage functions during the evolution of metabolic dysfunction-associated steatohepatitis (MASH). Results: In animal models of MASH, ICOS was selectively up-regulated on CD8+ T-cells in parallel with an expansion of ICOSL-expressing macrophages. An increase in circulating soluble ICOSL was also evident in patients with MASH as compared to healthy individuals. ICOSL knockout (ICOSL-/-) mice receiving choline/methionine deficient (MCD) diet for 6 weeks had milder steatohepatitis than wild type mice. MASH improvement was confirmed in mice fed with cholesterol-enriched Western diet for 24 weeks in which ICOSL deficiency greatly reduced liver fibrosis along with the formation of crown-like macrophage aggregates producing the pro-fibrogenic mediators osteopontin (OPN) and galectin-3 (Gal-3). These effects associated with a selective shewing of F4-80+/CD11bhigh monocyte-derived macrophages (MoMFs) expressing the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) to CD11blow/F4-80+ cells positive for the Kupffer cell marker C-type lectin-like type 2 receptor (CLEC-2), thus indicating an increased MoMF maturation toward monocyte-derived Kupffer cells. Conclusions: These results suggest that CD8+ T-cells interaction with monocyte-derived macrophages through ICOS/ICOSL critically supports a specific subset of TREM2+-expressing cells contributing to the evolution of steatohepatitis. The data also point ICOS/ICOSL dyad as a possible target for therapeutic interventions in MASH. [ABSTRACT FROM AUTHOR]

Fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix components in tissues and organs, leading to progressive architectural remodelling and contributing to the development of various diseases. Osteopontin (OPN), a highly phosphorylated glycoprotein, has been increasingly recognized for its involvement in the progression of tissue fibrosis. This review provides a comprehensive overview of the genetic and protein structure of OPN and focuses on our current understanding of the role of OPN in the development of fibrosis in the lungs and other tissues. Additionally, special attention is given to the potential of OPN as a biomarker and a novel therapeutic target in the treatment of fibrosis. [Display omitted] • Fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix produced by myofibroblasts. • Fibrosis is an irreversible process that leads to organ destruction and ultimately organ failure. • In fibrotic diseases, high levels of osteopontin were found and correlated with a more severe phenotype and worse prognosis. • Osteopontin is involved in the development of fibrotic diseases. • Osteopontin is a potential biomarker and novel therapeutic target for fibrotic diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma (MM) accounts for about 10% of all hematologic malignancies and is usually accompanied by severe bone disease. We analyzed the circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in newly diagnosed MM (NDMM) patients at diagnosis and in the course of treatment. Given the significantly higher levels of tested proteins at diagnosis, their correlations with the stage and grade of the disease, as well as their gradual decrease in the course of treatment, we suggest the applicability of these proteins as potential biomarkers for myeloma related bone disease (MBD) monitoring. The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls (p < 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation (p < 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others (p < 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly increased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with a reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Furthermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7 × 10−5) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC. [ABSTRACT FROM AUTHOR]

The osteogenic potential of mesenchymal stem cells (MSc) in axial spondyloarthritis (AxSpA) depends on the interplay of inflammation and multiple hormonal and local mechanical factors. In this study, MCs, derived from the adipose tissue of a healthy donor, were cultured under or without continuous mechanical load in the osteogenic differentiation medium with or without the addition of testosterone, cocktail of INF-γ/TNF-α/IL-22, or both. Real-time PCR for osteogenic transcription factors demonstrated that in the absence of INF-γ/TNF-α/IL-22, mechanical load causes significant upregulation of SPP1 (osteopontin), while the presence of the inflammatory cytokines almost completely abolishes this effect. In addition, exposure to INF-γ/TNF-α/IL-22 slightly upregulated BMP2, but suppressed the expression of ALPL, Col1A1, and SPP1, reinforcing the hypothesis that the inflammatory environment allows MSc to commit toward the IL-22-driven osteogenic differentiation but can restrict the later stages of osteogenesis. In summary, osteopontin can play a role in the pathogenesis of AxSpA, linking between mechanical load and pathological bone formation. [ABSTRACT FROM AUTHOR]

Objective: To analyze the relationship between serum glycosylphosphatidylinositol anchor attachment protein 1 (GPAA1), ferritin (SF), osteopontin (OPN) and the risk of acute lymphoblastic leukemia in children and evaluate the risk of thrombosis.Methods: 112 children with acute lymphoblastic leukemia admitted to our hospital from January 2017 to December 2022 were selected as the observation group, and 112 healthy children matching the gender and age of the observation group were selected as the control group.The expression levels of serum GPAA1, SF and OPN in the two groups were detected, the differences in the expression levels of serum GPAA1, SF and OPN in children with acute lymphoblastic leukemia with different risk levels were analyzed, and the occurrence of thrombosis in children with acute lymphoblastic leukemia was observed.The area under receiver operating characteristic curve (ROC) (AUC) was used to evaluate the efficacy of serum GPAA1, SF and OPN in predicting thrombus occurrence in children with acute lymphoblastic leukemia. Results: The expression levels of serum GPAA1, SF and OPN in observation group were higher than those in control group (P＜0.05) . The expression levels of serum GPAA1,SF and OPN in children with low-risk,medium-risk and high-risk acute lymphoblastic leukemia were significant (P＜0.05) . The expression levels of serum GPAA1, SF and OPN were positively correlated with the risk of childhood acute lymphoblastic leukemia by Spearman correlation analysis (P＜0.05) . Among 112 children with acute lymphoblastic leukemia, thrombosis occurred in 12 cases (10.71%) . Multivariate Logistic regression analysis showed that serum GPAA1,SF and OPN were independent predictors of thrombosis in children with acute lymphoblastic leukemia (P＜0.05) . According to ROC curve analysis, the AUC of serum GPAA1 and SF combined with OPN to predict thrombus occurrence in children with acute lymphoblastic leukemia was 0.901. Conclusion: Serum GPAA1, SF and OPN are closely related to the risk of acute lymphoblastic leukemia in children, and the combination of GPAA1, SF and OPN is effective in predicting thrombus occurrence in children, which has important guiding significance in the diagnosis and treatment of this disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by progressive accumulations of extracellular amyloid-beta (Aβ) aggregates from soluble oligomers to insoluble plaques and hyperphosphorylated intraneuronal tau, also from soluble oligomers to insoluble neurofibrillary tangles (NFTs). Tau and Aβ complexes spread from the entorhinal cortex of the brain to interconnected regions, where they bind pattern recognition receptors on microglia and astroglia to trigger inflammation and neurotoxicity that ultimately lead to neurodegeneration and clinical AD. Systemic inflammation is initiated by Aβ's egress into the circulation, which may be secondary to microglial activation and can confer both destructive and reparative actions. Microglial activation pathways and downstream drivers of Aβ/NFT neurotoxicity, including inflammatory regulators, are primary targets for AD therapy. Osteopontin (OPN), an inflammatory cytokine and biomarker of AD, is implicated in Aβ clearance and toxicity, microglial activation, and inflammation, and is considered to be a potential therapeutic target. Here, using the most relevant works from the literature, we review and contextualize the evidence for a central role of OPN and associated inflammation in AD. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular diseases (ASCVDs) are the most common and severe public health problem nowadays. Osteopontin (OPN) is a multifunctional glycoprotein highly expressed at atherosclerotic plaque, which has emerged as a potential biomarker of ASCVDs. OPN may act as an inflammatory mediator and/or a vascular calcification (VC) mediator, contributing to atherosclerosis progression and eventual plaque destabilization. In this article, we discuss the complex role of OPN in ASCVD pathophysiology, since many in vitro and in vivo experimental data indicate that OPN contributes to macrophage activation and differentiation, monocyte infiltration, vascular smooth muscle cell (VSMC) migration and proliferation and lipid core formation within atherosclerotic plaques. Most but not all studies reported that OPN may inhibit atherosclerotic plaque calcification, making it "vulnerable". Regarding clinical evidence, serum OPN levels may become a biomarker of coronary artery disease (CAD) presence and severity. Significantly higher OPN levels have been found in patients with acute coronary syndromes than those with stable CAD. In limited studies of patients with peripheral artery disease, circulating OPN concentrations may be predictive of future major adverse cardiovascular events. Overall, the current literature search suggests the contribution of OPN to atherosclerosis development and progression, but more robust evidence is required. [ABSTRACT FROM AUTHOR]

IntroductionHPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood.ObjectiveTo investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV− OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk.Materials and methodsA retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication.ResultsHPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV−positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV− OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs.ConclusionThis investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

Background: Type 2 diabetes mellitus is a condition in which the body is unable to use insulin effectively. This condition was previously known as non-insulin-dependent or adult-onset diabetes. Osteopontin (OPN) is a phosphorylated glycoprotein initially found in a secreted form in bones. Later, it was discovered that it also exists as an intracellular protein. Objectives: he study aimed to predict Osteopontin levels in type 2 diabetes mellitus patients without fatty liver disease. Results: The study found that group A had significantly higher levels of FBS, HbA1c, insulin, HOMA-IR, triglycerides, and VLDL compared to group B (P ≤ 0.05). Additionally, group A had significantly lower levels of HDL than group B. However, there were no significant differences in the levels of cholesterol, LDLc, and ALP between the two groups (P ≥ 0.05). The mean ±SD levels of Osteopontin were 23.66 for group A (DM with NAFLD),. 15.65 for group B (DM without NAFLD), and 5.43 for group C (control group ). This indicates a statistically significant difference (P≤0.05) in the mean ±SD levels of Osteopontin among the studied groups. Conclusion: All parameters are increased in patients with type 2 DM without nonalcoholic fatty liver disease compared to the control group. The recommended threshold for Osteopontin in predicting type 2 diabetes mellitus without non-alcoholic fatty acid liver disease is 9.31 ng/ml.

Abstract In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.

Abstract Background Idiopathic pulmonary fibrosis (IPF) affects West Highland white terriers (WHWTs). Osteopontin (SPP1) and fibronectin (FN1) are associated with human IPF and are overexpressed by bronchoalveolar lavage fluid (BALF) macrophages in dogs with IPF. Objective To investigate the value of these proteins as biomarkers of IPF. Animals West Highland white terriers (WHWTs) with IPF, control WHWTs, and terriers. Methods Cross‐sectional observational study. Immunohistochemistry was used to localize SPP1 and FN1 in lung tissue. Serum and BALF SPP1 and FN1 concentrations were measured using canine ELISA kits and compared between groups. Results Osteopontin stained ciliated epithelial cells, smooth muscular cells, and macrophages of all included dogs, and type‐II pneumocytes and extracellular matrix of all 12 diseased WHWTs, 4/6 control WHWTs, and none of the 3 terriers. Osteopontin serum concentration was higher in diseased WHWTs (n = 22; 2.15 ng/mL [0.74‐5.30]) compared with control WHWTs (n = 13; 0.63 ng/mL [0.41‐1.63]; P = .005) and terriers (n = 15; 0.31 ng/mL [0.19‐0.51]; P

Objective To explore the role of urinary osteopontin (uOPN) in predicting clinical responses to induction therapy and renal prognosis in adults with lupus nephritis (LN). Methods A total of 53 type Ⅲ/Ⅳ LN adults were recruited. At the same time, 24 healthy volunteers visiting our hospital for physical examination in the same period were selected as healthy control group. Levels of uOPN were determined by enzyme-linked immunosorbent assay (ELISA). Renal biopsies were performed at baseline and after induction therapy. According to the criteria of American College of Rheumatology (ACR), they were divided into two groups of clinical response or non-response. Patients with ≥50% improvement in renal activity index scores were selected as histological response group. Results Baseline and post-treatment levels of uOPN were significantly higher in LN patients than those in healthy controls [2.33(1.84, 2.83)mg/L, 2.07(1.55, 2.72)mg/L vs 0.94(0.70, 1.46)mg/L](P0.05). Multivariate Logistic regression analysis revealed that baseline uOPN was an independent predictor of histological response to LN induction therapy (P

Background. Diagnosis of an asymptomatic course of chronic viral hepatitis C (HCV) and the existing development of the fibrotic process by determining the marker capabilities of biochemical blood parameters (primarily osteopontin — OP) is an urgent issue in modern medicine. Purpose: to evaluate the prognostic value of biochemical blood markers for diagnosing an asymptoma­tic course of HCV and the existing fibrotic process. Materials and me­thods. Seventy-eight people were examined: 47 from the main group — 19 (40.4 %) women and 28 (59.6 %) men with chronic HCV, and 31 controls — 17 (54.8 %) women and 14 (45.2 %) men without chronic HCV. The median, as well as 25.0% and 75.0% quartiles and relative values were calculated for quantitative and qualitative measures, respectively. Predictors were determined using logistic regression analysis. Results. The data obtained by a univariate analysis indicate a significantly increased risk of develo­ping liver fibrosis on the background of chronic HCV, with alanine aminotransferase (ALT) levels increased by 1.037 times, aspartate aminotransferase (AST) by 1.051 times, gamma-glutamyl transferase (GGT) by 1.017 times; thymol turbidity test by 1.424 times; total protein by 1.162 times and OP by 3.002 times. With increased levels of triglycerides and very low-density lipoproteins, a significant decrease in these risks was found, by 74.7 and 94.7 %, respectively. A multivariate analysis found significantly increased risks of deve­loping liver fibrosis on the background of chronic HCV, with higher levels of AST, total protein, and OP (by 1.028, 1.195 and 2.510 times, respectively). Conclusions. With a significant liver damage by a fibrotic process (stage 3–4), as compared to stage 0–2, there is a probable predominance of biochemical liver markers in the blood of patients with HCV: ALT, AST, GGT, total protein and OP. AST, total protein, and OP were identified as reliable predictors of liver fibrosis. The developed mathematical model has high sensitivity and specificity: 87.5 and 83.9 %, respectively.

Abstract Background Excessive extracellular matrix (ECM) deposition in adipose tissue is a hallmark of fibrosis, leading to disrupted adipose tissue homeostasis and metabolic dysfunction. Hesperetin, a flavonoid compound, has shown promising anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, we investigated the anti-fibrotic effects of hesperetin, through targeting ECM components and matrix metalloproteinase enzymes. Methods 3T3-L1 cells were cultured in DMEM, containing 10% FBS and 1% penicillin/streptomycin. Cells were treated with a range of hesperetin concentrations, and the cell viability was determined using MTT assay. Subsequently, the expression of genes encoding collagen VI, osteopontin, matrix metalloproteinase-2 (Mmp-2) and Mmp-9 was analyzed using specific primers and real-time PCR technique. To evaluate protein levels of collagen VI and osteopontin, Western blotting was performed. Results Hesperetin affected the viability of 3T3-L1 adipocytes with IC50 of 447.4 µM, 339.2 µM and 258.8 µM (24 h, 48 and 72 h, respectively). Hesperetin significantly reduced the gene and protein expression of both collagen VI and osteopontin in 3T3-L1 pre-adipocytes, in a time- and dose-dependent manner. Hesperetin was also able to cause a remarkable decline in gene expression of Mmp2 and Mmp9. Conclusion Hesperetin could potently reduce the production of markers of adipose tissue fibrosis and might be considered a potential anti-fibrotic compound in obesity. Thus, hesperetin has the potency to be used for the treatment of obesity-associated fibrosis.

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis.

Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (≅600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.

Background: Behaviorally conditioned immune functions are suggested to be regulated by bidirectional interactions between CNS and peripheral immune system via the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic nervous system (SNS), and the parasympathetic nervous system (PNS). Since the current knowledge about biochemical pathways triggering conditioned immune enhancement is limited, the aim of this pilot study was gaining more insights into that. Methods: Rats were conditioned with camphor smell and poly I:C injection, mimicking a viral infection. Following stimulus re-exposure, animals were sacrificed at different time points, and neural tissues along the HPA axis was analyzed with a rat genome array together with plasma protein using Luminex analysis. Results: In the hypothalamus, we observed a strong upregulation of genes related to Wnt/β-catenin signaling (Otx2, Spp1, Fzd6, Zic1), monoaminergic transporter Slc18a2 and opioid-inhibitory G-protein Gpr88 as well as downregulation of dopaminergic receptors, vasoactive intestinal peptide Vip, and pro-melanin-concentrating hormone Pmch. In the pituitary, we recognized mostly upregulation of steroid synthesis in combination with GABAergic, cholinergic and opioid related neurotransmission, in adrenal glands, altered genes showed a pattern of activated metabolism plus upregulation of adrenoceptors Adrb3 and Adra1a. Data obtained from spleen showed a strong upregulation of immunomodulatory genes, chemo-/cytokines and glutamatergic/cholinergic neurotransmission related genes, as also confirmed by increased chemokine and ACTH levels in plasma. Conclusions: Our data indicate that in addition to the classic HPA axis, there could be additional pathways as e.g. the cholinergic anti-inflammatory pathway (CAIP), connecting brain and immune system, modulating and finetuning communication between brain and immune system.

Abstract Background Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. Methods Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above − 3.0 and no diet differences completed 12 weeks of RT. The participants’ diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion. Results After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p