-
The American Journal of Surgical... May 2024
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Osteonectin; Membrane Proteins
PubMed: 38357938
DOI: 10.1097/PAS.0000000000002190 -
BMC Oral Health Feb 2024Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC... (Comparative Study)
Comparative Study
BACKGROUND
Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC expression in odontogenic keratocyst (OKC), an odontogenic cyst with an aggressive nature. To the best of our knowledge, only one study has been investigated the expression of this protein in OKCs. This study aimed to characterize SPARC expression in OKCs. Additionally, to determine whether SPARC is associated with aggressive behavior in OKCs, SPARC expression in OKCs was compared with radicular cysts (RCs), dentigerous cysts (DCs) and calcifying odontogenic cysts (COCs). These odontogenic cysts showed no or less aggressive behavior.
METHODS
SPARC expression was evaluated in 38 OKCs, 39 RCs, 35 DCs and 14 COCs using immunohistochemistry. The percentages of positive cells and the intensities of immunostaining in the epithelial lining and the cystic wall were evaluated and scored.
RESULTS
Generally, OKCs showed similar staining patterns to RCs, DCs and COCs. In the epithelial lining, SPARC was not detected, except for ghost cells in all COCs. In the cystic wall, the majority of positive cells were fibroblasts. Compared between 4 groups of odontogenic cysts, SPARC expression in OKCs was significantly higher than those of RCs (P < 0.001), DCs (P < 0.001) and COCs (P = 0.001).
CONCLUSIONS
A significant increase of SPARC expression in OKCs compared with RCs, DCs and COCs suggests that SPARC may play a role in the aggressive behavior of OKCs.
Topics: Humans; Dentigerous Cyst; Odontogenic Cysts; Odontogenic Tumors; Osteonectin; Radicular Cyst
PubMed: 38347494
DOI: 10.1186/s12903-024-03978-4 -
Biomolecules Jan 2024Mammalian cells have evolved to function under Earth's gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for...
Mammalian cells have evolved to function under Earth's gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth's gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed enhanced stress responses as well as autophagy-like behavior. To ascertain if the secretome from SPC-flown NSCs contained molecules inducing these responses, we incubated naïve, non-starved NSCs in a medium containing SPC-NSC secretome. We found a four-fold increase in stress responses. Proteomic analysis of the secretome revealed that the protein of the highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which induces endoplasmic reticulum (ER) stress, resulting in the cell's demise. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting the SPARC metabolism. Although we did not establish a direct relationship between microgravity-induced stress and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based protein design.
Topics: Animals; Humans; Osteonectin; Proteomics; Space Flight; Neural Stem Cells; Neurons; Mammals
PubMed: 38254665
DOI: 10.3390/biom14010065 -
The FEBS Journal Apr 2024Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus...
Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high-fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.
Topics: Animals; Humans; Mice; Citric Acid; Diet, High-Fat; Obesity; Osteonectin; Pancreatic Neoplasms
PubMed: 38245817
DOI: 10.1111/febs.17058 -
The American Journal of Surgical... May 2024
Topics: Humans; Biomarkers, Tumor; Diagnosis, Differential; Epithelioid Cells; Lung Neoplasms; Membrane Proteins; Mesothelioma; Mesothelioma, Malignant; Osteonectin
PubMed: 38223954
DOI: 10.1097/PAS.0000000000002178 -
International Journal of Biological... Feb 2024This study delves into the potential of chito-oligosaccharides (COS) to promote osteoblast differentiation and prevent osteoporosis, utilizing experiments with mouse...
Chitosan derived chito-oligosaccharides promote osteoblast differentiation and offer anti-osteoporotic potential: Molecular and morphological evidence from a zebrafish model.
This study delves into the potential of chito-oligosaccharides (COS) to promote osteoblast differentiation and prevent osteoporosis, utilizing experiments with mouse MSCs and the zebrafish model. The preliminary biocompatibility study affirms the non-toxic nature of COS across various concentrations. In the osteoblast differentiation study, COS enhances ALP activity and calcium deposition at the cellular level. Moreover, COS induces the upregulation of molecular markers, including Runx2, Type I collagen, ALP, osteocalcin, and osteonectin in mouse MSCs. Zebrafish studies further demonstrate COS's anti-osteoporotic effects, showcasing its ability to expedite fin fracture repair, vertebral mineralization, and bone mineralization in dexamethasone-induced osteoporosis models. The scale regenerative study reveals that COS mitigates the detrimental effects of dexamethasone induced osteoclastic activity, reducing TRAP and hydroxyproline levels while elevating the expression of Runx2a MASNA isoform, collagen2α, OC, and ON mRNAs. Additionally, COS enhances calcium and phosphorus levels in regenerated scales, impacting the bone-healthy calcium-to‑phosphorus ratio. The study also suggests that COS modulates the MMP3-Osteopontin-MAPK signaling pathway. Overall, this comprehensive investigation underscores the potential of COS to prevent and treat osteoporosis. Its multifaceted cellular and molecular effects, combined with in vivo bone regeneration and repair, propose that COS may be effective in addressing osteoporosis and related bone disorders. Nonetheless, further research is imperative to unravel underlying mechanisms and optimize clinical applications.
Topics: Mice; Animals; Zebrafish; Chitosan; Calcium; Osteogenesis; Osteoporosis; Cell Differentiation; Dexamethasone; Osteoblasts; Phosphorus
PubMed: 38199551
DOI: 10.1016/j.ijbiomac.2024.129250 -
Pathology, Research and Practice Feb 2024Prostate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered...
BACKGROUND
Prostate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered to be promising prognostic marker of PCa due to its involvement in various cancer processes.
MATERIALS AND METHODS
study was conducted on PCa surgical primary tumor samples, obtained from 84 patients. Level of SPARC mRNA expression was estimated using RT-qPCR. To identify SPARC protein (osteonectin) in prostate tissue, immunohistochemical analysis was conducted. Bioinformatical analysis was performed on UALCAN and TNMplot resources.
RESULTS
bioinformatical analysis demonstrated that SPARC mRNA levels are decreased in PCa samples, in comparison to normal tissue. In patients with lymph node metastases its levels are 1.26 times higher; p = 4.66E, than in N0 category. Ex vivo study demonstrated that SPARC expression was elevated on both mRNA and protein levels in PCa patients with lymph node metastases (by 2.34 and 1.91, respectively, p < 0.05). We established higher levels of SPARC mRNA and protein in PCa patients with T3 tumors, as well as high Gleason score. Estimation of survival rates demonstrated that PCa patients with a high level of SPARC mRNA and protein have decreased overall 2-year survival.
CONCLUSIONS
SPARC protein was overexpressed on mRNA and protein levels in patients with presence of lymph node metastases and higher Gleason score of tumors. Also, both mRNA and protein upregulation were associated with worse survival rates. The current study has therefore provided further evidence that SPARC is indeed linked to the prognosis and aggressiveness of human PCa.
Topics: Male; Humans; Prognosis; Osteonectin; Lymphatic Metastasis; Prostatic Neoplasms; RNA, Messenger
PubMed: 38199134
DOI: 10.1016/j.prp.2023.155053 -
Journal of Controlled Release :... Feb 2024Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich...
Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich in cysteine (SPARC) has high binding affinity to albumin and has been shown to enhance the penetration and uptake of albumin-based drug carriers in tumors. Here, we developed a strategy to alter the tumor microenvironment (TME) by upregulating SPARC to enhance the delivery efficiency of albumin-based drug carriers into tumors. We prepared albumin nanoparticles encapsulating an NF-κB controllable CRISPR activation system (SP-NPs). SP-NPs achieved tumor-selective SPARC upregulation by responding to the highly activated NF-κB in tumor cells. Whereas a single dose of SP-NPs only modestly upregulated SPARC expression, serial administration of SP-NPs created a positive feedback loop that induced progressive increases in SPARC expression as well as tumor cell uptake and tumor penetration of the nanoparticles in vitro, in organoids, and in subcutaneous tumors in vivo. Additionally, pre-treatment with SP-NPs significantly enhanced the anti-tumor efficacy of Abraxane, a commercialized albumin-bound paclitaxel nanoformulation. Our data provide evidence that modulating SPARC in the TME can enhance the efficiency of albumin-based drug delivery to solid tumors, which may result in new strategies to increase the efficacy of nanoparticle-based cancer drugs.
Topics: Humans; NF-kappa B; Osteonectin; Albumins; Drug Delivery Systems; Neoplasms; Drug Carriers; Albumin-Bound Paclitaxel; Tumor Microenvironment
PubMed: 38184232
DOI: 10.1016/j.jconrel.2023.12.057 -
PloS One 2023The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria...
The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria critical-size defects. DMB and DCC were prepared using a previously published method. The granule size used ranged between 500 and 750 μm. A total of forty-eight Sprague-Dawley rats were divided into two groups (n = 24). A pair of 5 mm diameter defects were created on the calvaria of the rats in the right and left parietal bone in both groups. Group A animals received DMB granules and Group B received DCC granules in the right parietal defect side while the left parietal untreated defect acted as sham surgery for both groups. Four animals per group were euthanized in a CO2 chamber at day 7, 14 and 21 post-surgery and the calvaria implantation site biopsy harvested was subjected to osteogenic gene expression analysis. Another four animals per group were euthanized at days 15, 30 and 60 post surgery and the calvaria implantation site biopsy harvested was subjected to histological, immunohistochemistry, RAMAN spectroscopy and Micro-CT analysis at the mentioned time points. Statistical analysis was conducted using t-tests and ANOVA. Histomorphometry showed significantly higher new bone formation in the DCC sites (p<0.05) compared to DMB. Both DMB and DCC implantation sites showed distinct staining for osteocalcin and osteopontin proteins compared to their respective sham sites. By day 21 after implantation, DCC sites demonstrated significantly elevated mRNA levels of osteonectin (p<0.001), osteopontin (p<0.001), osteocalcin (p<0.0001), ALP (p<0.01), and BMP-2 (p<0.001) compared to DMB. However, VEGF expression showed no significant differences at this time point between the two groups. Micro-CT analysis also showed enhanced defect closure and higher bone density in DCC implanted sites while RAMAN spectra demonstrated increased abundance of collagen and bone minerals, especially, PO43- ions than DMB. In conclusion, both DMB and DCC granules demonstrated favorable osteogenic potential in critical-sized defects, with DCC exhibited superior osteoconductive, osteoinductive and osteogenesis properties.
Topics: Rats; Animals; Cattle; Osteogenesis; Rats, Sprague-Dawley; Osteopontin; Osteocalcin; Skull; Bone Regeneration; Minerals
PubMed: 38127838
DOI: 10.1371/journal.pone.0294291 -
Frontiers in Immunology 2023Serum C-reactive protein (CRP) has been found elevated during COVID-19 infection, and associated with systematic inflammation as well as a poor clinical outcome....
Serum C-reactive protein (CRP) has been found elevated during COVID-19 infection, and associated with systematic inflammation as well as a poor clinical outcome. However, how did CRP participated in the COVID-19 pathogenesis remains poorly understood. Here, we report that serum C-reactive protein (CRP) levels are correlated with megakaryocyte marker genes and could regulate immune response through interaction with megakaryocytes. Molecular dynamics simulation through ColabFold showed a reliable interaction between monomeric form of CRP (mCRP) and the secreted protein acidic and rich in cysteine (SPARC). The interaction does not affect the physiological activities of SPARC while would be disturbed by pentamerization of CRP. Interplay between SPARC and mCRP results in a more intense immune response which may led to poor prognosis. This study highlights the complex interplay between inflammatory markers, megakaryocytes, and immune regulation in COVID-19 and sheds light on potential therapeutic targets.
Topics: Humans; C-Reactive Protein; Cells, Cultured; COVID-19; Inflammation; Osteonectin
PubMed: 38077346
DOI: 10.3389/fimmu.2023.1259381