Glucagon-like peptide-1 receptor promotes osteoblast differentiation of dental pulp stem cells and bone formation in a zebrafish scale regeneration model.

Bone cells express the glucagon-like peptide 1 receptor (GLP-1R). However, its presence and role in human dental pulp derived stem cells (hDPSCs) remains elusive. Hence, in the current study, we isolated hDPSCs and differentiated them into osteoblasts, where GLP-1R expression was found to be upregulated during osteoblast differentiation. GLP-1 receptor agonist, liraglutide peptide treatment, increased osteoblast differentiation in hDPSCs by increasing calcium deposition, ALP activity, and osteoblast marker genes, Runx2, type 1 col, osteonectin, and osteocalcin. Furthermore, activation of long non-coding RNA (LncRNA) LINC00968 and microRNA-3658 signalling increased Runx2 expression. Specifically, liraglutide increased LncRNA-LINC00968 expression while decreasing miR-3658 expression. LINC00968 targets miR-3658, and miR-3658 targets Runx2. Additionally, in an in-vivo study, zebrafish scale regeneration model, liraglutide promoted calcium deposition, osteoblastic cell count, collagen 1α, osteonectin, osteocalcin, runx2a MASNA isoform expression (transcribed from promoter P1), and Ca/P ratio in scales. Overall, GLP-1R activation promotes osteoblast differentiation via Runx2/LncRNA-LINC00968/miR-3658 signalling in hDPSCs and promotes bone formation in zebrafish scale regeneration.

Oligodendrocyte Progenitors Display Enhanced Proliferation and Autophagy after Space Flight.

Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the consequences of long-term space missions. Here we examined the behavior of oligodendrocyte progenitors (OLPs) after space flight using time-lapse microscopy. We show that most OLPs divided more than ground control (GC) counterparts did. Nonetheless, a subpopulation of OLPs flown to space presented a significant increase in autophagic cell death. Examination of the proteomic profile of the secretome of space flown OLPs (SPC-OLPs) revealed that the stress protein heat shock protein-90 beta "HSP-90ß" was the 5th most enriched (6.8 times) and the secreted protein acidic and rich in cysteine "SPARC" was the 7th most enriched (5.2 times), with respect to ground control cells. SPARC induces endoplasmic reticulum stress, which leads to autophagy. Given the roles and importance of these two proteins in mammalian cells' metabolism, their upregulation may hold the key to modulating cell proliferation and autophagy, in order to mitigate ICP and VIIP during and after space missions.

SPARC is a decoy counterpart for c­Fos and is associated with osteoblastic differentiation of bone marrow stromal cells by inhibiting adipogenesis.

Secreted protein acidic and rich in cysteine (SPARC), also called basement­membrane protein 40 or osteonectin, is a matricellular protein that is abundant not only in bone tissue as a non­collagenous protein but is also ubiquitously expressed in non­calcified tissue. SPARC is located intracellularly and disruption of the Sparc gene has been reported to reduce bone formation and increase fat tissue; however, the mechanism by which SPARC inhibits adipogenesis remains unclear. The present study evaluated the intracellular function of SPARC in adipogenesis using the bone marrow stromal cell line ST2. When ST2 cells with low SPARC production were cloned, intrinsic activator protein­1 (AP­1) activity was markedly higher, mineralized nodule formation was significantly lower and lipid accumulation was significantly increased compared with in the parental ST2 cells. Forced expression of secreted SPARC with the signal peptide­coding sequences of wild­type Sparc or preprotrypsin in SPARC­low ST2 cells significantly reduced AP­1 transcription activity; however, these reductions were not observed in the absence of signal peptide sequences. Recombinant SPARC, produced using Brevibacillus brevis, specifically bound to c­Fos but not c­Jun and inhibited the binding of c­Fos/c­Jun to a TPA­response element sequence. These data suggested that SPARC was incorporated into the cells from the extracellular spaces and serves an intracellular role as a decoy counterpart for c­Fos, as well as being associated with osteoblastogenesis through the inhibition of adipogenesis. These findings may provide new insights into regenerative medicine.

Low Bcl-2 is a robust biomarker of sensitivity to nab-paclitaxel in Ewing sarcoma.

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) shows potent preclinical anticancer activity in pediatric solid tumors such as Ewing sarcoma, rhabdomyosarcoma and neuroblastoma, but responses in clinical trials have been modest. In this work, we aimed to discover a rational biomarker-based approach to select the right candidate patients for this treatment. We assessed the efficacy of nab-paclitaxel in 27 patient-derived xenografts (PDX), including 14 Ewing sarcomas, five rhabdomyosarcomas and several other pediatric solid tumors. Response rate (partial or complete response) was remarkable in rhabdomyosarcomas (four of five) and Ewing sarcomas (four of 14). We addressed several predictive factors of response to nab-paclitaxel such as the expression of the secreted protein acidic and rich in cysteine (SPARC), chromosomal stability of cancer cells and expression of antiapoptotic members of the B-cell lymphoma-2 (Bcl-2) family of proteins such as Bcl-2, Bcl-xL, Bcl-W and Mcl-1. Protein (immunoblotting) and gene expression of SPARC correlated positively, while immunoblotting and immunohistochemistry expression of Bcl-2 correlated negatively with the efficacy of nab-paclitaxel in Ewing sarcoma PDX. The negative correlation of Bcl-2 immunoblotting signal and activity was especially robust (r = 0.8352; P = 0.0007; Pearson correlation). Consequently, we evaluated pharmacological strategies to inhibit Bcl-2 during nab-paclitaxel treatment. We observed that the Bcl-2 inhibitor venetoclax improved the activity of nab-paclitaxel in highly resistant Bcl-2-expressing Ewing sarcoma PDX. Overall, our results suggest that low Bcl-2 expression could be used to select patients with Ewing sarcoma sensitive to nab-paclitaxel, and Bcl-2 inhibitors could improve the activity of this drug in Bcl-2-expressing Ewing sarcoma.

Imaging of Indocyanine Green-Human Serum Albumin (ICG-HSA) Complex in Secreted Protein Acidic and Rich in Cysteine (SPARC)-Expressing Glioblastoma.

Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.

The role of SPARC/ON in human osteosarcoma.

The human osteosarcoma is a malignant tumor of the arthro-skeletal system. It has been recognized that it is the most common malignancy followed by the Ewing sarcoma or primitive neuroectodermal tumor. The prognosis is worrisome and is not preserved by the use of classical chemotherapy drugs. High rates of recurrence and metastases often accompany this malignant tumor. Chemotherapy often fails because of the onset of multidrug resistance, even though the mechanism to reach chemotherapy resistance is still intriguing and contains unclear pathways. The secreted protein acidic and rich in cysteine (SPARC) or osteonectin (ON) (SPARC/ON) has been associated with poor prognosis in several malignant neoplasms. In this mini-review, we are going to highlight the role of SPARC/ON in human osteosarcoma. Extracellular vesicles are fundamental in cell-to-cell communication. We suggest that a liquid biopsy targeting SPARC/ON may be critical to implement in the surveillance of patients with this malignant bony neoplasm.

Immunological role and prognostic value of SPARCL1 in pan-cancer analysis.

Background: Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) was a kind of extracellular matrix glycoprotein. SPARCL1 was strongly inhibited in most cancers. However, the potential functions of SPARCL1 in the pan-cancer cohort have not been widely studied. Methods: We evaluated the transcriptional level and the prognostic value of SPARCL1 in 33 types of cancer and revealed the relationship between genetic alterations of SPARCL1 and the tumor mutation burden. Meanwhile, we assessed the correlations between SPARCL1 and tumor-infiltrating lymphocytes across cancers. Results: The transcriptional level of SPARCL1 was inhibited in most cancers. Although SPARCL1 was down-regulated in most cancers, SPARCL1 might play a protective or detrimental role in different cancers. We demonstrated that mutation count was elevated in the altered SPARCL1 group in several cancers. Additionally, we found a significant positive correlation between SPARCL1 and macrophage infiltration levels in most cancers. Especially, marker sets of M2 macrophages were strongly related to SPARCL1 in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, and pancreatic adenocarcinoma. Conclusion: Our study found that SPARCL1 might work as a biomarker for prognosis and immune infiltration in pan-cancer analysis.

The Matricellular Protein SPARC Decreases in the Lacrimal Gland At Adulthood and During Inflammation.

Purpose: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein abundantly expressed in basement membranes and capsules surrounding a variety of organs and tissues. It mediates extracellular matrix organization and has been implicated in cell contraction. Here, we evaluated the expression of SPARC in the murine lacrimal gland at adulthood and during inflammation. Methods: Lacrimal glands of young mice (4-6 weeks old) and adult mice (32-40 weeks old) were used for extraction of DNA, RNA, and protein. The presence of SPARC was assessed by quantitative PCR, ELISA, and immunofluorescence microscopy. 5-Methylcytosine and DNA methylation were evaluated using ELISA and bisulfite genomic sequencing, respectively. The effects of cytokines and inflammation in Sparc expression were evaluated in vitro and in the non-obese diabetic (NOD) mouse model of Sjögren's syndrome. Results: The mRNA and protein levels of SPARC were downregulated in lacrimal glands of mature adult mice presenting age-related histological alterations such as increased deposition of lipofuscin and lipids. Epigenetic analyses indicated that glands in adult mice contain higher levels of global DNA methylation and show increased hypermethylation of specific CpG sites within the Sparc gene promoter. Analysis of smooth muscle actin (SMA)-green fluorescent protein (GFP) transgenic mice revealed that SPARC localizes primarily to myoepithelial cells within the gland. Treatment of myoepithelial cells with IL-1ß or TNF-α and the development of inflammation in the NOD mice led to decreased transcription of Sparc. Conclusions: SPARC is a novel matricellular glycoprotein expressed by myoepithelial cells in the lacrimal gland. Loss of SPARC during adulthood and chronic inflammation might have detrimental consequences on myoepithelial cell contraction and the secretion of tear fluid.

Introduce a rotational robust optimization framework for spot-scanning proton arc (SPArc) therapy.

Objective. Proton dosimetric uncertainties resulting from the patient's daily setup errors in rotational directions exist even with advanced image-guided radiotherapy techniques. Thus, we developed a new rotational robust optimization SPArc algorithm (SPArcrot) to mitigate the dosimetric impact of the rotational setup error in Raystation ver. 6.02 (RaySearch Laboratory AB, Stockholm, Sweden).Approach.The initial planning CT was rotated ±5° simulating the worst-case setup error in the roll direction. The SPArcrotuses a multi-CT robust optimization framework by taking into account of such rotational setup errors. Five cases representing different disease sites were evaluated. Both SPArcoriginaland SPArcrotplans were generated using the same translational robust optimized parameters. To quantitatively investigate the mitigation effect from the rotational setup errors, all plans were recalculated using a series of pseudo-CT with rotational setup error (±1°/±2°/±3°/±5°). Dosimetric metrics such as D98% of CTV, and 3D gamma analysis were used to assess the dose distribution changes in the target and OARs.Main results.The magnitudes of dosimetric changes in the targets due to rotational setup error were significantly reduced by the SPArcrotcompared to SPArc in all cases. The uncertainties of the max dose to the OARs, such as brainstem, spinal cord and esophagus were significantly reduced using SPArcrot. The uncertainties of the mean dose to the OARs such as liver and oral cavity, parotid were comparable between the two planning techniques. The gamma passing rate (3%/3 mm) was significantly improved for CTV of all tumor sites through SPArcrot.Significance.Rotational setup error is one of the major issues which could lead to significant dose perturbations. SPArcrotplanning approach can consider such rotational error from patient setup or gantry rotation error by effectively mitigating the dose uncertainties to the target and in the adjunct series OARs.

SPARC plays an important role in the oviposition and nymphal development in Nilaparvata lugens Stål.

BACKGROUND: The brown planthopper (Nilaparvata lugens Stål)is a notorious rice pest in many areas of Asia. Study on the molecular mechanisms underlying its development and reproduction will provide scientific basis for effective control. SPARC (Secreted Protein, Acidic and Rich in Cysteine) is one of structural component of the extracellular matrix, which influences a diverse array of biological functions. In this study, the gene for SPARC was identified and functionally analysed from N.lugens. RESULTS: The result showed that the NlSPARC mRNA was highly expressed in fat body, hemolymph and early embryo. The mortality increased significantly when NlSPARC was downregulated after RNA interference (RNAi) in 3 ~ 4th instar nymphs. Downregulation of NlSPARC in adults significantly reduced the number of eggs and offspring, as well as the transcription level of NlSPARC in newly hatched nymphs and survival rate in progeny. The observation with microanatomy on individuals after NlSPARC RNAi showed smaller and less abundant fat body than that in control. No obvious morphological abnormalities in the nymphal development and no differences in development of internal reproductive organ were observed when compared with control. CONCLUSION: NlSPARC is required for oviposition and nymphal development mainly through regulating the tissue of fat body in N.lugens. NlSPARC could be a new candidate target for controlling the rapid propagation of N.lugens population. Our results also demonstrated that the effect of NlSPARC RNAi can transfer to the next generation in N.lugens.

Tracking matricellular protein SPARC in extracellular vesicles as a non-destructive method to evaluate lipid-based antifibrotic treatments.

Uncovering the complex cellular mechanisms underlying hepatic fibrogenesis could expedite the development of effective treatments and noninvasive diagnosis for liver fibrosis. The biochemical complexity of extracellular vesicles (EVs) and their role in intercellular communication make them an attractive tool to look for biomarkers as potential alternative to liver biopsies. We developed a solid set of methods to isolate and characterize EVs from differently treated human hepatic stellate cell (HSC) line LX-2, and we investigated their biological effect onto naïve LX-2, proving that EVs do play an active role in fibrogenesis. We mined our proteomic data for EV-associated proteins whose expression correlated with HSC treatment, choosing the matricellular protein SPARC as proof-of-concept for the feasibility of fluorescence nanoparticle-tracking analysis to determine an EV-based HSCs' fibrogenic phenotype. We thus used EVs to directly evaluate the efficacy of treatment with S80, a polyenylphosphatidylcholines-rich lipid, finding that S80 reduces the relative presence of SPARC-positive EVs. Here we correlated the cellular response to lipid-based antifibrotic treatment to the relative presence of a candidate protein marker associated with the released EVs. Along with providing insights into polyenylphosphatidylcholines treatments, our findings pave the way for precise and less invasive diagnostic analyses of hepatic fibrogenesis.

Functionalization of Covalent Organic Frameworks with Peptides by Polymer-Assisted Surface Modification and the Application for Protein Detection.

Although covalent organic frameworks (COFs) have received extensive attention for biomedical research due to their unique properties, their application is still hindered by the challenges of incorporating COFs with functional biomolecules. Since peptides have shown advantages in biomedical applications, herein, we propose the functionalization of COFs with peptides by a polymer-assisted surface modification strategy. Furthermore, a method based on the peptide-functionalized COFs for protein detection has also been developed to demonstrate their application potential. With the help of the polymers, peptides and horseradish peroxidase are attached onto COFs with a high surface density, and the developed method has achieved simple and sensitive detection of the secreted protein acidic and rich in cysteine. We speculate that the facile method proposed in this work to prepare peptide-functionalized COFs can not only benefit protein detection but also promote more biomedical applications of COFs.

[SPARC Overexpression Enhances the Sensitivity of SKM-1 Cells to Ara-C by Regulating CPBP/MLKL].

OBJECTIVE: To investigate the effect of SPARC gene overexpression on the chemotherapeutic sensitivity of AML-MDS cell line SKM-1 to Ara-C and to further explore its mechanism. METHODS: Subjects were divided into 6 groups: SKM-1 cells (Control), Negative control (LV-NC), SPARC overexpression (LV-SPARC), SKM-1 cells+30 ng/ml Ara-C (30 ng/ml Ara-C), LV-NC+30 ng/ml Ara-C and LV-SPARC+30 ng/ml Ara-C. Cell activity was detected by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry, mRNA expression levels of SPARC, CPBP and MLKL were detected by RT-qPCR, and the expression levels of related protein were detected by Western blot. RESULTS: After co-treatment with SPARC overexpression and Ara-C, the cell viability decreased and apoptosis increased significantly, with obvious up-regulation of Bax and down-regulation of BCL-2 (P<0.05). Compared with the control group, the cell cycle of LV-SPARC+30 ng/ml Ara-C group was significantly arrested in S phase with obvious down-regulation of CDK2 and up-regulation of p27KIP1 (P<0.05). Compared with LV-SPARC group and 30 ng/ml Ara-C group, the mRNA and protein expression levels of CPBP and MLKL (p-MLKL) were significantly elevated in LV-SPARC+30 ng/ml Ara-C group (P<0.05). In addition, after co-treatment with SPARC overexpression and Ara-C, the protein expression level of p-AKT decreased and the protein expression level of p53 increased (P<0.05). CONCLUSION: SPARC overexpression enhanced the sensitivity of SKM-1 cells to Ara-C and promoted cell cycle arrest and apoptosis, the mechanism of which may be related to the regulation of CPBP/MLKL pathway.

A Tissue Engineering Acoustophoretic (TEA) Set-up for the Enhanced Osteogenic Differentiation of Murine Mesenchymal Stromal Cells (mMSCs).

Quickly developing precision medicine and patient-oriented treatment strategies urgently require novel technological solutions. The randomly cell-populated scaffolds usually used for tissue engineering often fail to mimic the highly anisotropic characteristics of native tissue. In this work, an ultrasound standing-wave-based tissue engineering acoustophoretic (TEA) set-up was developed to organize murine mesenchymal stromal cells (mMSCs) in an in situ polymerizing 3-D fibrin hydrogel. The resultant constructs, consisting of 17 cell layers spaced at 300 µm, were obtained by continuous wave ultrasound applied at a 2.5 MHz frequency. The patterned mMSCs preserved the structured behavior within 10 days of culturing in osteogenic conditions. Cell viability was moderately increased 1 day after the patterning; it subdued and evened out, with the cells randomly encapsulated in hydrogels, within 21 days of culturing. Cells in the structured hydrogels exhibited enhanced expression of certain osteogenic markers, i.e., Runt-related transcription factor 2 (RUNX2), osterix (Osx) transcription factor, collagen-1 alpha1 (COL1A1), osteopontin (OPN), osteocalcin (OCN), and osteonectin (ON), as well as of certain cell-cycle-progression-associated genes, i.e., Cyclin D1, cysteine-rich angiogenic inducer 61 (CYR61), and anillin (ANLN), when cultured with osteogenic supplements and, for ANLN, also in the expansion media. Additionally, OPN expression was also augmented on day 5 in the patterned gels cultured without the osteoinductive media, suggesting the pro-osteogenic influence of the patterned cell organization. The TEA set-up proposes a novel method for non-invasively organizing cells in a 3-D environment, potentially enhancing the regenerative properties of the designed anisotropic constructs for bone healing.

A SPARC-ling link to inflammaging.

Adipocyte derived SPARC induces pro-inflammatory changes to macrophages, leading to aging that can be reduced by caloric restriction.

bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling.

INTRODUCTION: Basic fibroblast growth factor (bFGF) plays a critical role in odontoblast differentiation and dentin matrix deposition, thereby aiding pulpo-dentin repair and regeneration. OBJECTIVES: The purpose of this study was to clarify the effects of bFGF on plasminogen activation factors, TIMP-1), ALP; and SPARC (osteonectin) expression/production of stem cells from apical papilla (SCAP) in vitro; and the involvement of MEK/ERK, p38, Akt, and TAK1 signaling. METHODS: SCAP were exposed to bFGF with/without pretreatment and co-incubation with various signal transduction inhibitors (U0126, SB203580, LY294002, and 5Z-7-oxozeaenol). The expression of FGF receptors (FGFRs), PAI-1, uPA, p-ERK, p-TAK1, and p-p38 was analyzed via immunofluorescent staining. The gene expression and protein secretion of SCAP were determined via real-time PCR and ELISA. ALP activity was evaluated via ALP staining. RESULTS: SCAP expressed FGFR1, 2, 3, and 4. bFGF stimulated the PAI-1, uPA, uPAR, and TIMP-1 mRNA expression (p < 0.05). bFGF induced PAI-1, uPA, and soluble uPAR production (p < 0.05) but suppressed the ALP activity and SPARC production (p < 0.05) of SCAP. bFGF stimulated ERK, TAK1, and p38 phosphorylation of SCAP. U0126 (a MEK/ERK inhibitor) and 5Z-7-oxozeaenol (a TAK1 inhibitor) attenuated the bFGF-induced PAI-1, uPA, uPAR, and TIMP-1 expression and production of SCAP, but SB203580 (a p38 inhibitor) did not. LY294002, SB203580, and 5Z-7oxozeaenol could not reverse the inhibition of ALP activity caused by bFGF. Interestingly, U0126 and 5Z-7-oxozeaenol prevented the bFGF-induced decline of SPARC production (p < 0.05). CONCLUSION: bFGF may regulate fibrinolysis and matrix turnover via modulation of PAI-1, uPA, uPAR, and TIMP-1, but bFGF inhibited the differentiation (ALP, SPARC) of SCAP. These events are mainly regulated by MEK/ERK, p38, and TAK1. Combined use of bFGF and SCAP may facilitate pulpal/root repair and regeneration via regulation of the plasminogen activation system, migration, matrix turnover, and differentiation of SCAP.

Skip the buffet, for SPARC's sake.

Caloric restriction (CR) reduces inflammation and the incidence of chronic diseases, thereby extending healthspan and lifespan. In this issue of Immunity, Ryu et al. (2022) propose that reduction of SPARC, a matricellular protein, during CR offers beneficial effects by reducing SPARC-driven inflammatory phenotypes in macrophages.

Growth hormone/IGF-I-dependent signaling restores decreased expression of the myokine SPARC in aged skeletal muscle.

Skeletal muscle exerts many beneficial effects on the human body including the contraction-dependent secretion of peptides termed myokines. We have recently connected the myokine secreted protein acidic and rich in cysteine (SPARC) to the formation of intramuscular adipose tissue (IMAT) in skeletal muscle from aged mice and humans. Here, we searched for inducers of SPARC in order to uncover novel treatment approaches for IMAT. Endurance exercise in mice as well as forskolin treatment in vitro only modestly activated SPARC levels. However, through pharmacological treatments in vitro, we identified IGF-I as a potent inducer of SPARC expression in muscle cells, likely through a direct activation of its promoter via phosphatidylinositol 4,5-bisphospate 3-kinase (PI3K)-dependent signaling. We employed two different mouse models of growth hormone (GH)/IGF-I deficiency to solidify our understanding of the relationship between IGF-I and SPARC in vivo. GH administration robustly increased intramuscular SPARC levels (3.5-fold) in GH releasing hormone receptor-deficient mice and restored low intramuscular SPARC expression in skeletal muscle from aged mice. Intramuscular glycerol injections induced higher levels of adipocyte markers (adiponectin, perilipin) in aged compared to young mice, which was not prevented by GH treatment. Our study provides a roadmap for the study of myokine regulation during aging and demonstrates that the GH/IGF-I axis is critical for SPARC expression in skeletal muscle. Although GH treatment did not prevent IMAT formation in the glycerol model, targeting SPARC by exercise or by activation of IGF-I signaling might offer a novel therapeutic strategy against IMAT formation during aging. KEY MESSAGES : IGF-I regulates the myokine SPARC in muscle cells directly at the promoter level. GH/IGF-I is able to restore the decreased SPARC levels in aged skeletal muscle. The glycerol model induces higher adipocyte markers in aged compared to young muscle. GH treatment does not prevent IMAT formation in the glycerol model.

A pH/H2 O2 /MMP9 Time-Response Gel System with Sparchigh Tregs Derived Extracellular Vesicles Promote Recovery After Acute Myocardial Infarction.

Regulatory T cells overexpressing SPARC (secreted protein acidic and cysteine rich) (Sparchigh Tregs) can help repair infarct tissues after acute myocardial infarction (AMI). This research demonstrates that Sparchigh Treg-derived extracellular vesicles (EVs) effectively improved cardiac function through proinflammatory factors IL-1ß, IL-6, and TNF-α inhibition and collagen synthesis related gene Col3a1 promotion in AMI; moreover, a composite hydrogel-EVs system (DHPM(4APPC)_EVs) is designed based on Sparchigh Treg-derived EVs with CXCR2 overexpressing and pH/H2 O2 /MMP9 temporally responsive gel microspheres. In AMI, due to the levels of chemokine, pH, H2 O2 , and MMP9 enzymes in the infarct area, DHPM(4APPC)_EVs can effectively target the infarct area, release the loaded EVs, form the gel to capture the released EVs, and slowly release the captured EVs, contribute to promote EVs to stay in the infarct area for a long time to play the repair function, so as to reduce myocardial injury and promote the improvement of cardiac function. The proposed system in this research provides a potential approach for the treatment of AMI in the future.

SPARC in hematologic malignancies and novel technique for hematological disease with its abnormal expression.

Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is a matricellular protein involved in several biological processes including cell adhesion, growth factor availability, extracellular matrix remodeling and immune-regulation. SPARC has also been associated with a variety of diseases including diabetes, colon cancer, and leukemia. The expression of SPARC in different diseases exhibits some degree of ambiguity, especially in hemopathies. Herein, we review the current expression and effects of SPARC in various hematologic disorders with respect to nanoparticle albumin bound innovative therapies and related diagnostic research, providing a clinical perspective on the use of NAB technology in the frontier treatment of hematologic diseases.