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Pathology, Research and Practice Jun 2024Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its...
Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly its anti-inflammatory and antioxidant potential. However, due to its low water solubility, it exhibits poor bioavailability. In order to overcome this problem, in the current study, we have employed liposomal technology to encapsulate curcumin with the aim of enhancing its therapeutic efficacy. The curcumin-loaded liposomes (PlexoZome®) were tested on a cigarette smoke extract-induced Chronic Obstructive Pulmonary Disease (COPD) in vitro model using minimally immortalized human bronchial epithelial cells (BCiNS1.1). The anti-senescence and anti-inflammatory properties of PlexoZome® were explored. 5 µM PlexoZome® curcumin demonstrated anti-senescent activity by decrease in X-gal positive cells, and reduction in the expression of p16 and p21 in immunofluorescence staining. Moreover, PlexoZome® curcumin also demonstrated a reduction in proteins related to senescence (osteopontin, FGF basic and uPAR) and inflammation (GM-CSF, EGF and ST2). Overall, the results clearly demonstrate the therapeutic potential of curcumin encapsulated liposomes in managing CSE induced COPD, providing a new direction to respiratory clinics.
PubMed: 38909404
DOI: 10.1016/j.prp.2024.155423 -
International Journal of Medical... 2024Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be...
Bone marrow-derived mesenchymal stem cells (MSCs), which are capable of differentiating into osteoblasts, are used in effective regenerative therapies. MSCs must be prompted to differentiate into osteoblasts for MSC transplantation to be effective. In this study, osteoblast differentiation markers involved in bone formation were evaluated to investigate the stress resistance of bone marrow-derived rat MSCs to dexamethasone and hypoxia and their ability to differentiate into osteoblasts. MSCs were allowed to differentiate into osteoblasts for 21 days in three different environments (dexamethasone treatment, hypoxic conditions [1% oxygen], or both). Osteoblast differentiation potential was evaluated according to alkaline phosphatase levels and a mineralisation assay. Immunofluorescence staining was used to determine the protein expression of the osteoblast differentiation markers type I collagen and osteopontin. MSCs differentiated into osteoblasts under hypoxic conditions but differentiated more slowly upon treatment with dexamethasone and dexamethasone plus hypoxia relative to the control. MSCs preconditioned with dexamethasone or hypoxia and then allowed to differentiate into osteoblasts under similar conditions differentiated comparably to control MSCs. MSCs that developed resistance to dexamethasone or hypoxia differentiated more quickly into osteoblasts than those that did not. The findings suggest that increasing the resistance of MSCs to stress by preconditioning them via dexamethasone or hypoxia exposure could result in more rapid differentiation into osteoblasts following transplantation.
Topics: Dexamethasone; Mesenchymal Stem Cells; Animals; Osteoblasts; Cell Differentiation; Rats; Cell Hypoxia; Osteogenesis; Cells, Cultured; Alkaline Phosphatase; Humans; Mesenchymal Stem Cell Transplantation; Collagen Type I; Male
PubMed: 38903930
DOI: 10.7150/ijms.91222 -
Frontiers in Cell and Developmental... 2024Vestibular sensory epithelia contain type I and type II sensory hair cells (HCI and HCII). Recent studies have revealed molecular markers for the identification of these...
Vestibular sensory epithelia contain type I and type II sensory hair cells (HCI and HCII). Recent studies have revealed molecular markers for the identification of these cells, but the precise composition of each vestibular epithelium (saccule, utricle, lateral crista, anterior crista, posterior crista) and their postnatal maturation have not been described in detail. Moreover, methods to study this maturation are not well developed. We obtained total HCI and HCII counts in adult rats and studied the maturation of the epithelia from birth (P0) to postnatal day 28 (P28). Adult vestibular epithelia hair cells were found to comprise ∼65% HCI expressing osteopontin and PMCA2, ∼30% HCII expressing calretinin, and ∼4% HCII expressing SOX2 but neither osteopontin nor calretinin. At birth, immature HCs express both osteopontin and calretinin. P28 epithelia showed an almost adult-like composition but still contained 1.3% of immature HCs. In addition, we obtained free-floating 3D cultures of the epithelia at P1, which formed a fluid-filled cyst, and studied their survival and maturation up to day 28 (28 DIV). These cultures showed good HC resiliency and maturation. Using an enriched medium for the initial 4 days, a HCI/calretinin+-HCII ratio close to the ratio was obtained. These cultures are suitable to study HC maturation and mature HCs in pharmacological, toxicological and molecular research.
PubMed: 38895157
DOI: 10.3389/fcell.2024.1404894 -
Cancers May 2024The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas. (Review)
Review
BACKGROUND
The study aims to investigate the role of hypoxia-inducible factors (HIFs) in the development, progression, and therapeutic potential of glioblastomas.
METHODOLOGY
The study, following PRISMA guidelines, systematically examined hypoxia and HIFs in glioblastoma using MEDLINE (PubMed), Web of Science, and Scopus. A total of 104 relevant studies underwent data extraction.
RESULTS
Among the 104 studies, global contributions were diverse, with China leading at 23.1%. The most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) was frequently studied, followed by hypoxia-inducible factor 2 alpha (HIF2α), osteopontin, and cavolin-1. Commonly associated factors and pathways include glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) receptors, vascular endothelial growth factor (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target of rapamycin (mTOR) pathway, and reactive oxygen species (ROS). HIF expression correlates with various glioblastoma hallmarks, including progression, survival, neovascularization, glucose metabolism, migration, and invasion.
CONCLUSION
Overcoming challenges such as treatment resistance and the absence of biomarkers is critical for the effective integration of HIF-related therapies into the treatment of glioblastoma with the aim of optimizing patient outcomes.
PubMed: 38893207
DOI: 10.3390/cancers16112089 -
Cureus May 2024Osteosarcoma (OS), a primary malignant bone tumor, poses significant challenges in diagnosis and prognosis. It is a painful medical burden, and treating it is still a... (Review)
Review
Osteosarcoma (OS), a primary malignant bone tumor, poses significant challenges in diagnosis and prognosis. It is a painful medical burden, and treating it is still a difficult issue. Osteopontin (OPN), a multifunctional extracellular matrix protein, has emerged as a promising biomarker in this context. This systematic review explores the role of OPN as a diagnostic and prognostic marker in OS, highlighting its potential in enhancing early detection, monitoring disease progression, and predicting patient outcomes. Various studies have demonstrated elevated levels of OPN in OS patients, correlating with tumor aggressiveness, metastatic potential, and poor prognosis. In addition, OPN's involvement in tumor microenvironment regulation and metastatic processes underscores its clinical relevance as a biomarker. For this systematic review, comprehensive literature searches were conducted in the PubMed databases for research published between the database's establishment and November 11, 2022. Out of the nine studies that were available for analysis, a higher level of OPN in primary osteogenic sarcoma patients indicates a poorer prognosis and higher incidence of metastasis. OS has not shown commensurable progress with concerns to treatment approches and survical outcomes. However, the discovery of a biological marker that can predict metastasis and severity will be a groundbreaking development for advancements in OS diagnosis and treatment. Therefore, understanding the intricate interplay between OPN and OS pathogenesis holds promise for improving patient management and developing targeted therapeutic strategies.
PubMed: 38887353
DOI: 10.7759/cureus.60544 -
Stem Cell Research & Therapy Jun 2024Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing...
Mechanical stimulation-induced purinome priming fosters osteogenic differentiation and osteointegration of mesenchymal stem cells from the bone marrow of post-menopausal women.
BACKGROUND
Mechanical stimulation (MS) significantly increases the release of adenine and uracil nucleotides from bone marrow-derived mesenchymal stem cells (BM-MSCs) undergoing osteogenic differentiation. Released nucleotides acting via ionotropic P2X7 and metabotropic P2Y purinoceptors sensitive to ATP and UDP, respectively, control the osteogenic commitment of BM-MSCs and, thus, bone growth and remodelling. Yet, this mechanism is impaired in post-menopausal (Pm)-derived BM-MSCs, mostly because NTPDase3 overexpression decreases the extracellular accumulation of nucleotides below the levels required to activate plasma membrane-bound P2 purinoceptors. This prompted us to investigate whether in vitro MS of BM-MSCs from Pm women could rehabilitate their osteogenic commitment and whether xenotransplantation of MS purinome-primed Pm cells promote repair of critical bone defects in an in vivo animal model.
METHODS
BM-MSCs were harvested from the neck of femora of Pm women (70 ± 3 years old) undergoing total hip replacement. The cells grew, for 35 days, in an osteogenic-inducing medium either submitted (SS) or not (CTR) to MS (90 r.p.m. for 30 min) twice a week. Increases in alkaline phosphatase activity and in the amount of osteogenic transcription factors, osterix and osteopontin, denoted osteogenic cells differentiation, while bone nodules formation was ascertain by the alizarin red-staining assay. The luciferin-luciferase bioluminescence assay was used to quantify extracellular ATP. The kinetics of the extracellular ATP (100 µM) and UDP (100 µM) catabolism was assessed by HPLC. The density of P2Y and P2X7 purinoceptors in the cells was assessed by immunofluorescence confocal microscopy. MS-stimulated BM-MSCs from Pm women were xenotransplanted into critical bone defects drilled in the great trochanter of femora of one-year female Wistar rats; bone repair was assessed by histological analysis 10 days after xenotransplantation.
RESULTS
MS-stimulated Pm BM-MSCs in culture (i) release 1.6-fold higher ATP amounts, (ii) overexpress P2X7 and P2Y purinoceptors, (iii) exhibit higher alkaline phosphatase activity and overexpress the osteogenic transcription factors, osterix and osteopontin, and (iv) form larger bone nodules, than CTR cells. Selective blockage of P2X7 and P2Y purinoceptors with A438079 (3 µM) and MRS 2578 (0.1 µM), respectively, prevented the osteogenic commitment of cultured Pm BM-MSCs. Xenotransplanted MS purinome-primed Pm BM-MSCs accelerated the repair of critical bone defects in the in vivo rat model.
CONCLUSIONS
Data suggest that in vitro MS restores the purinergic cell-to-cell communication fostering the osteogenic differentiation and osteointegration of BM-MSCs from Pm women, a strategy that may be used in bone regeneration and repair tactics.
Topics: Female; Mesenchymal Stem Cells; Humans; Osteogenesis; Animals; Cell Differentiation; Aged; Postmenopause; Rats; Bone Marrow Cells; Mesenchymal Stem Cell Transplantation; Sp7 Transcription Factor; Cells, Cultured; Transcription Factors; Rats, Wistar
PubMed: 38886849
DOI: 10.1186/s13287-024-03775-4 -
Scientific Reports Jun 2024Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year,...
Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.
Topics: Diabetes Mellitus, Type 2; Animals; Rats; Protein Interaction Maps; Collagen Type IV; Osteopontin; Gene Regulatory Networks; Disease Models, Animal; Computational Biology; Gene Expression Profiling; Male; Humans; Gene Ontology; Non-alcoholic Fatty Liver Disease; Signal Transduction
PubMed: 38886539
DOI: 10.1038/s41598-024-64857-0 -
Scientific Reports Jun 2024Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe...
Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.
Topics: Adult; Animals; Female; Humans; Male; Epilepsy, Temporal Lobe; Gene Expression Profiling; Gene Regulatory Networks; Hippocampal Sclerosis; MicroRNAs; Osteopontin; Protein Interaction Maps; SOXB1 Transcription Factors
PubMed: 38871732
DOI: 10.1038/s41598-024-63541-7 -
Pharmacological Research Jul 2024The osteopontin-derived peptide FOL-005 stimulates hair growth. Using ligand-receptor glyco-capture technology we identified neuropilin-1 (NRP-1), a known co-receptor...
The osteopontin-derived peptide FOL-005 stimulates hair growth. Using ligand-receptor glyco-capture technology we identified neuropilin-1 (NRP-1), a known co-receptor for vascular endothelial growth factor (VEGF) receptors, as the most probable receptor for FOL-005 and the more stable analogue FOL-026. X-ray diffraction and microscale thermophoresis analysis revealed that FOL-026 shares binding site with VEGF in the NRP-1 b1-subdomain. Stimulation of human umbilical vein endothelial cells with FOL-026 resulted in phosphorylation of VEGFR-2, ERK1/2 and AKT, increased cell growth and migration, stimulation of endothelial tube formation and inhibition of apoptosis in vitro. FOL-026 also promoted angiogenesis in vivo as assessed by subcutaneous Matrigel plug and hind limb ischemia models. NRP-1 knock-down or treatment of NRP-1 antagonist EG00229 blocked the stimulatory effects of FOL-026 on endothelial cells. Exposure of human coronary artery smooth muscle cells to FOL-026 stimulated cell growth, migration, inhibited apoptosis, and induced VEGF gene expression and VEGFR-2/AKT phosphorylation by an NRP-1-dependent mechanism. RNA sequencing showed that FOL-026 activated pathways involved in tissue repair. These findings identify NRP-1 as the receptor for FOL-026 and show that its biological effects mimic that of growth factors binding to the VEGF receptor family. They also suggest that FOL-026 may have therapeutical potential in conditions that require vascular repair and/or enhanced angiogenesis.
Topics: Neuropilin-1; Humans; Human Umbilical Vein Endothelial Cells; Animals; Neovascularization, Physiologic; Osteopontin; Cell Movement; Vascular Endothelial Growth Factor Receptor-2; Cell Proliferation; Myocytes, Smooth Muscle; Male; Peptides; Vascular Endothelial Growth Factor A; Apoptosis; Mice, Inbred C57BL; Protein Binding; Ischemia; Mice; Angiogenesis
PubMed: 38871237
DOI: 10.1016/j.phrs.2024.107259 -
European Review For Medical and... May 2024Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or environmental factors that modify buccal eutrophism. In daily clinical practice, an increase in the prevalence of PI (8%) determined the need to establish the PI causes and set optimal therapeutic strategies. The interleukin family (IL-1), a group of cytokines, triggers and perpetuates peri-implantitis. Therefore, they could be used as biomarkers for diagnosis and treatment. This systematic review aimed to analyze the correlation between IL-1 allelic polymorphism (IL-1A -889, IL-1β -511, IL-1β +3954) and the PI disease.
MATERIALS AND METHODS
Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: "dental implants"; "periimplantitis"; "interleukin-IL-1"; "polymorphism"; "perimplant bone loss". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A meta-analysis was conducted on five of 40 review articles. p-values, confidence intervals (CI), and Odds ratios (OR) were assessed. In 4 articles, the p-value was lower than 0.05, confirming the statistical significance of the result.
RESULTS
The prevalence of the selected studies reported the existence of a causal association between polymorphisms of IL-1 and the onset of peri-implantitis, especially for IL-1 allelic variants associated with further polymorphic genes encoding for IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMP)-8, IL-1Na, IL-8, IL-18, osteopontin (OPN). In addition, the presence of the IL-1 polymorphism and PI is particularly higher in smokers, diabetes, and autoimmune disease patients.
CONCLUSIONS
The detection of salivary biomarkers is, therefore, a diagnostic tool with a high potential to intercept the PI early and act with appropriate and non-invasive treatment. Due to the continued technological innovation in biomarkers and diagnostic sciences, further studies are needed to investigate the role of these biochemical mediators. The results of studies and the recent technological innovation in biomarkers and diagnostic sciences will allow further research to investigate the role of these biochemical mediators.
Topics: Humans; Peri-Implantitis; Polymorphism, Genetic; Interleukin-1; Dental Implants
PubMed: 38856132
DOI: 10.26355/eurrev_202405_36293