Calcified Nodules Research Articles

Mogroside V Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells from Diabetic Mice by Altering MicroRNA Profiles.

Mogroside V (MV), a triterpene glycoside, exhibits diverse biological functions. However, its ability to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under diabetic conditions is yet to be elucidated. To study the regulation of osteogenic differentiation of BMSCs in diabetic mice by MV and determine the potential mechanism. BMSCs were isolated from both normal (referred to as N-BMSCs) and diabetic (referred to as DM-BMSCs) C57BL/6 mice. DM-BMSCs were treated with different concentrations of MV for varying durations, and cell viability was detected using the cell counting kit-8 assay. Following 2 weeks of osteogenic induction, osteogenic differentiation capability was evaluated using alizarin red S staining, alkaline phosphatase (ALP) activity analysis, and quantitative real-time reverse transcription polymerase chain reaction. Furthermore, the microRNA (miRNA) expression profiles of N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV were tested using high-throughput sequencing. Treatment with MV enhanced the viability of DM-BMSCs and mitigated the reduction of calcium nodule deposition, ALP activity, and mRNA expression of ALP, osteocalcin, and runt-related transcription factor 2. Of the analyzed miRNAs, miR-10b-5p was the only one that exhibited differential expression in N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV. An analysis of the top four protein clusters based on KEGG suggested that the target genes of differentially expressed miRNAs were closely linked to the PI3K/AKT pathway. MV significantly enhances the viability and osteogenic differentiation of BMSCs under diabetic conditions. The alteration of miRNA profiles provides a foundation for further research into the regulatory role of miRNAs and MV in this process.

Osteogenerative and corrosion-decelerating teriparatide-mediated strontium–zinc phosphate hybrid coating on biodegradable zinc–copper alloy for orthopaedic applications

Zinc–copper (ZnCu) alloys recently showed great potential as biodegradable materials for bone implants thanks to their excellent mechanical strength, biosafety, and promising bioactivities. However, bare ZnCu alloys exhibited poor cytocompatibility and osteointegration. Moreover, the biological functions of ZnCu remain to be corroborated. Herein, the teriparatide (PTH)-mediated strontium–zinc phosphate (SrZnP) organic–inorganic hybrid coating was fabricated on the surface of ZnCu substrate via a chemical conversion method to contain the release of Zn ions and improve biofunctionality in osteogenesis. The characteristics of the hybrid coating were optimised by adjusting the amount of PTH molecules added. A dense and homogenous coating with micellar crystal micro-/nano-structure was obtained. The coated samples showed a significantly decreased corrosion rate and a more uniform corrosion mode, effectively suppressing the release of Zn2+. Additionally, the coated ZnCu enhanced the proliferation of bone marrow mesenchymal stem cells (BMSCs), promoted the expression of alkaline phosphatase and the formation of calcium nodules, and upregulated the levels of osteogenic-related genes. More important, the hybrid coating activated the classic osteogenic signalling pathway of BMP-2/Smad1/Runx2 and Sirt1/Runx2 to induce the osteogenic differentiation of BMSCs. These appealing features can be mainly attributed to the constituents of released Zn2+, Sr2+, and PTH molecules in the control, as well as the unique topographical characteristics of the coatings. Taken together, the PTH&SrZnP hybrid coating could be a promising option for surface modification of biodegradable metallic Zn for orthopaedic applications.

Histological Findings in the Eyes of Abcc6 Knockout Rat Model of Pseudoxanthoma Elasticum.

To describe the ocular findings of murine pseudoxanthoma elasticum (PXE) models with ATP-binding cassette subfamily C member 6 (Abcc6) gene knockout. This experiment was conducted in four Abcc6-/- rats and compared with six wild-type Abcc6+/+ control rats. The animals underwent necropsy at 6 months of age. Histological examination of the eyes was performed. Histological examination of eight eyes from four Abcc6-/- rats revealed multiple nodular foci of calcification in the uvea, sclera, and conjunctiva, focally in perivascular distribution, as well as linear and nodular calcification of Bruch's membrane. Calcific foci were not associated with inflammation in the knockout rats. There was no evidence of calcification in control eyes. The Abcc6-/- rat model shows that PXE can affect multiple ocular tissues beyond the calcification in Bruch's membrane noted in human eyes. Nodular calcific foci probably correspond to comet lesions seen in patients with PXE. The presence of ectopic calcium without inflammation distinguishes it from inflammatory calcium deposition in atherosclerosis. Further studies are needed to determine why PXE does not cause inflammatory infiltration. The Abcc6-/- murine model may be suitable for studying ocular PXE pathophysiology and ectopic calcification and developing effective therapies.

Self-restoring cryogels used for the repair of hemorrhagic bone defects by modulating blood clots

Bleeding from severe traumatic bone defects poses a significant threat to patient survival, and conventional hemostatic agents prove inadequate for addressing bone defects when pressure application is not feasible. Therefore, the development of a bio-multifunctional material with outstanding hemostatic and osteogenic performances is highly desirable. In this study, chitosan/hydroxyapatite nanowires cryogels (CSHAn) were fabricated via schiff base reaction and electrostatic interaction. These CSHAn cryogels demonstrate an impressive absorption capacity, reaching up to 5387 %, and possess considerable mechanical strength, quantified at 167.92 kPa, along with significant compressive recovery capabilities. CSHAn cryogels demonstrate superior blood-clotting ability, enhanced blood cell and platelet adhesion, and activation compared to gelatin sponges. Moreover, in vitro cellular assessments indicate that the developed CSHAn2 exhibits favorable cytocompatibility and significantly promote osteogenesis by upregulating the formation of alkaline phosphatase and calcium nodules. Taken together, this multi-functional cryogels is potentially valuable for clinical applications towards hemorrhagic bone defect repair.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Polylysine-derived carbon quantum dots modulate T lymphocyte responses for periodontitis treatment

Periodontitis, a common chronic inflammatory disease, is characterized by T cell responses leading to gradual alveolar bone loss and eventual tooth mobility or loss. Herein, polylysine-derived carbon quantum dots (PLL-CQDs) are synthesized via the pyrolysis method to facilitate the recovery of periodontal bone loss induced by periodontitis by modulating T cell phenotype. The PLL-CQDs, characterized by small particle size (2.31 ± 0.70 nm) and fluorescence properties, preserved the positive charge of PLL, affirming successful preparation. In vitro studies revealed that PLL-CQDs significantly increased T cell proliferation in a concentration-dependent manner, while effectively suppressing differentiation into CD4+ phenotype. Furthermore, they promoted alkaline phosphatase expression and calcium nodule formation in MC3T3-E1 cells, indicating potential for periodontal bone regeneration. In vivo experiments demonstrated that PLL-CQDs mitigated alveolar bone resorption and modulated periodontal tissue inflammation. Overall, PLL-CQDs exhibited the ability to regulate T cell differentiation and expedite periodontal bone healing, offering promising implications for periodontitis treatment and suggesting novel strategies for addressing immune-associated bone diseases using CQDs.

Axillary Lymph Nodal Calcifications due to Systemic Amyloidosis.

Axillary Lymph Nodal Calcifications due to Systemic Amyloidosis.

The IFT80/Hedgehog Pathway Regulates the Osteogenic-adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated. This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH. Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression. RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation. There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.

Effects of Tenascin-C on Dental Pulp Tissue in Mice In Vivo And on The Proliferation and Differentiation of Dental Pulp Stem Cells into Odontoblasts and Calcification In Vitro

This study aimed to investigate the effects of tenascin-C (TN-C) on dental pulp tissue and on dental pulp stem cells (DPSCs). In in vivo studies, A collagen sponge with phosphate-buffered saline (PBS) for the control group or with TN-C for the experimental group was placed over the dental pulp of mice. The root pulp was excised at 7 and 21 days postoperatively and was observed microscopically using HE staining and immunohistochemistry. Inflammatory cells were found in the entire pulp tissue in the control group but no inflammatory cells were identified in the pulp tissue in the TN-C-treated experimental group. Further, nesting-positive cells at 7 days and dentin sialo phosphoprotein (DSPP)-positive cells at 21 days were seen in the experimental group. In in vitro studies, DPSCs were cultured in a medium with or without TN-C, after which the proliferation rate of DPSCs was measured mRNA expression levels were examined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the formation of calcified nodules was investigated using alizarin red staining. There was no significant difference in the cell proliferation rate of DPSCs between the experimental and control groups during day 3 or 5, using the proliferation rate on day 1 as the baseline value. The expression of nesting mRNA on day 7 was significantly higher in the experimental group than in the control group (P&lt;0.05), but the expression of osteocalcin (OCN) mRNA was significantly higher in the control group than in the experimental group (P&lt;0.05). More calcified nodules formed and the area of calcified nodules in the control group was significantly greater than in the TN-C-treated experimental group on day 14 and day 21 (P &lt; 0.05). These results suggest that TN-C regulates inflammation during the healing process in the dental pulp and induces the differentiation of dental pulp into odontoblast-like cells. Further, TN-C promotes the early differentiation of DPSCs into odontoblast-like cells, which suggests that TN-C may further contribute to the inhibition of excessive dentin formation. From the above, TN-C is involved in differentiating dental pulp into mineralized tissue-forming cells and may have a beneficial effect in treatments that utilize this function

A case of symmetrical subepidermal calcified nodules on the eyelids

Dear Editor, Subepidermal calcified nodules (SCN), are typically asymptomatic, solitary, and idiopathic cutaneous calcinosis. We report a case with two SCN with a symmetrical distribution, where a single nodule was located on the medial aspect of each of the bilateral upper eyelids in a teenage male. [...]

Differences in the response of normal oral mucosa, oral leukoplakia, oral squamous cell carcinoma-derived mesenchymal stem cells, and epithelial cells to photodynamic therapy

ObjectiveThe objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. MethodsHOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. ResultsOM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. ConclusionsOLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.

Unknown Case: Breast and Axillary Lymph Node Calcifications.

Unknown Case: Breast and Axillary Lymph Node Calcifications.

Atorvastatin reduces calcification in valve interstitial cells via the NF-κB signalling pathway by promoting Atg5-mediated autophagy.

Aortic valve calcification (AVC) is a common cardiovascular disease and a risk factor for sudden death. However, the potential mechanisms and effective therapeutic drugs need to be explored. Atorvastatin is a statin that can effectively prevent cardiovascular events by lowering cholesterol levels. However, whether atorvastatin can inhibit AVC by reducing low-density lipoprotein (LDL) and its possible mechanism of action require further exploration. In the current study, we constructed an in vitro AVC model by inducing calcification of the valve interstitial cells. We found that atorvastatin significantly inhibited osteogenic differentiation, reduced the deposition of calcium nodules in valve interstitial cells, and enhanced autophagy in calcified valve interstitial cells, manifested by increased expression levels of the autophagy proteins Atg5 and LC3B-II/I and the formation of smooth autophagic flow. Atorvastatin inhibited the NF-κB signalling pathway and the expression of inflammatory factors mediated by NF-κB in calcified valve interstitial cells. The activation of the NF-κB signalling pathway led to the reversal of atorvastatin's effect on enhancing autophagy and alleviating valve interstitial cell calcification. In conclusion, atorvastatin inhibited the NF-κB signalling pathway by upregulating autophagy, thereby alleviating valve interstitial cell calcification, which was conducive to improving AVC.

Long non-coding RNA FGD5 antisense RNA 1 targets Baculovirus inhibitor 5 via microRNA-497-5p to alleviate calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is featured by thickening and calcification of the aortic valve. Osteoblast differentiation is a crucial step in valve calcification. Long non-coding RNAs (LncRNAs) participate in the osteogenic differentiation of mesenchymal cells. However, the character of lncRNA FGD5 antisense RNA 1 (FGD5-AS1) in CAVD is uncertain. After collection of human aortic valve tissue samples, detection of FGD5-AS1, microRNA (miR)-497-5p and Baculovirus inhibitor 5 (BIRC5) was conducted. Valve mesenchymal cells were isolated from CAVD patients and induced to differentiate to osteoblasts, and transfected with FGD5-AS1, miR-497-5p and BIRC5 plasmids. Detection of the alkaline phosphatase activity was after osteogenic induction of human aortic valve interstitial cells (hAVICs); Detection of the degree of calcium nodules and osteoblast differentiation markers (RUNX2 and OPN) was conducted. After establishment of a mouse model of CAVD, detection of the thickness of aortic valve leaflets, and the degree of calcification of the valve leaflets, and evaluation of echocardiographic parameters were implemented. Experimental data manifested in CAVD patients, lncRNAFGD5-AS1 and BIRC5 were reduced, but miR-497-5p was elevated; Enhancing lncRNA FGD5-AS1 or repressing miR-497-5p mitigated CAVD by restraining osteogenic differentiation; LncRNA FGD5-AS1 sponged miR-497-5p to target BIRC5; Repressive BIRC5 turned around the therapeutic action of elevated FGD5-AS1 or depressed miR-497-5p on hAVICs; Enhancive FGD5-AS1 in vivo was available to reduce ApoE-/- mouse CAVD induced via high cholesterol diet. All in all, lncRNAFGD5-AS1 targets BIRC5 via miR-497-5p to alleviate CAVD.

Calcified Nodules in Non-Culprit Lesions with Acute Coronary Syndrome Patients.

Calcified nodules (CN) have been linked to unfavorable clinical outcomes. However, there is a lack of systematic studies on non-culprit lesions with CN in patients with acute coronary syndromes (ACS). This study aims to investigate the frequency, distribution, predictors, and outcomes of CN in non-culprit lesions among ACS patients. We included 376 ACS patients who received successful stent placement in their culprit lesions. Intravascular ultrasound (IVUS) was performed to evaluate non-culprit lesions in left main arteries and all three coronary arteries (CA). CN was defined as accumulations of small nodular calcium deposits exhibiting a convex shape protruding into the lumen. CNs was identified in 16.9% (121 of 712) per artery and 26.9% (101 of 376) per patient. They were predominantly located at the mid portion of the right coronary artery (26.3%) and the bifurcation site (59.9%). Patients with CN were older (63.57 8.43 vs. 57.98 7.15, p 0.001) and had a higher prevalence of diabetes mellitus (55.4% vs. 42.2%, p = 0.022). However, there were no significant differences in baseline characteristics observed after propensity score matching (PSM). Multivariate analysis revealed that CN were independently associated with major adverse cardiovascular events (MACE) both before and after PSM (hazard ratio (HR): 0.341, 95% confidence interval (95% CI): 0.140-0.829, p = 0.018; HR: 0.275, 95% CI: 0.108-0.703, p = 0.007, respectively). During the observational period of 19.35 10.59 months, the occurrence of MACE was significantly lower in patients with CN before and after PSM (5.9% vs. 16.7%, p = 0.046; 4.0% vs. 18.1%, p = 0.011; respectively). CN in non-culprit lesions with ACS patients was prevalent and caused fewer adverse clinical outcomes.

Effect of graphene oxide/ poly-L-lactic acid composite scaffold on the biological properties of human dental pulp stem cells

BackgroundTissue engineering has attracted recent attention as a promising bone repair and reconstruction approach. Dental pulp stem cells (DPSCs) are pluripotent and can differentiate into bone cells with the correct environment and substrate. Therefore, suitable scaffold materials are essential for fabricating functional three-dimensional (3D) tissue and tissue regeneration. Composite scaffolds consisting of biodegradable polymers are very promising constructs. This study aims to verify the biological function of human DPSCs seeded onto composite scaffolds based on graphene oxide (GO) and poly-L-lactic acid (PLLA).MethodsThe surface morphology was observed under scanning electron microscopy (SEM). Chemical composition was evaluated with Fourier transform infrared (FTIR) spectroscopy. The biocompatibility of GO/PLLA scaffolds was assessed using phalloidin staining of cytoskeletal actin filaments, live/dead staining, and a CCK-8 assay. The effect of GO/PLLA scaffolds on cell osteogenic differentiation was detected through ALP staining, ALP activity assays, and alizarin red S staining, complemented by quantitative real-time PCR (qRT-PCR) analysis.ResultsOur data showed that GO and PLLA are successfully integrated and the GO/PLLA scaffolds exhibit favorable bioactivity and biocompatibility towards DPSCs. Additionally, it was observed that the 0.15% GO/PLLA scaffold group promoted DPSC proliferation and osteogenic differentiation by forming more calcium nodules, showing a higher intensity of ALP staining and ALP activity, and enhancing the expression levels of differentiation marker genes RUNX2 and COL1.ConclusionsThese results demonstrate that the GO/PLLA scaffold is a feasible composite material suitable for cell culture and holds promising applications for oral bone tissue engineering.

Enhancing osteoblast proliferation and bone regeneration by poly (amino acid)/selenium-doped hydroxyapatite

Among various biomaterials employed for bone repair, composites with good biocompatibility and osteogenic ability had received increasing attention from biomedical applications. In this study, we doped selenium (Se) into hydroxyapatite (Se-HA) by the precipitation method, and prepared different amounts of Se-HA-loaded poly (amino acid)/Se-HA (PAA/Se-HA) composites (0, 10 wt%, 20 wt%, 30 wt%) by in-situ melting polycondensation. The physical and chemical properties of PAA/Se-HA composites were characterized by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and their mechanical properties. XRD and FT-IR results showed that PAA/Se-HA composites contained characteristic peaks of PAA and Se-HA with amide linkage and HA structures. DSC and TGA results specified the PAA/Se-HA30 composite crystallization, melting, and maximum weight loss temperatures at 203.33 °C, 162.54 °C, and 468.92 °C, respectively, which implied good thermal stability. SEM results showed that Se-HA was uniformly dispersed in PAA. The mechanical properties of PAA/Se-HA30 composites included bending, compressive, and yield strengths at 83.07 ± 0.57, 106.56 ± 0.46, and 99.17 ± 1.11 MPa, respectively. The cellular responses of PAA/Se-HA composites in vitro were studied using bone marrow mesenchymal stem cells (BMSCs) by cell counting kit-8 assay, and results showed that PAA/Se-HA30 composites significantly promoted the proliferation of BMSCs at the concentration of 2 mg ml−1. The alkaline phosphatase activity (ALP) and alizarin red staining results showed that the introduction of Se-HA into PAA enhanced ALP activity and formation of calcium nodule. Western blotting and Real-time polymerase chain reaction results showed that the introduction of Se-HA into PAA could promoted the expression of osteogenic-related proteins and mRNA (integrin-binding sialoprotein, osteopontin, runt-related transcription factor 2 and Osterix) in BMSCs. A muscle defect at the back and a bone defect at the femoral condyle of New Zealand white rabbits were introduced for evaluating the enhancement of bone regeneration of PAA and PAA/Se-HA30 composites. The implantation of muscle tissue revealed good biocompatibility of PAA and PAA/Se-HA30 composites. The implantation of bone defect showed that PAA/Se-HA30 composites enhanced bone formation at the defect site (8 weeks), exhibiting good bone conductivity. Therefore, the PAA-based composite was a promising candidate material for bone tissue regeneration.

Coronary artery calcification: concepts and clinical applications.

Vascular calcification is an important hallmark of atherosclerosis. Coronary artery calcification (CAC) implies the presence of coronary artery disease (CAD), irrespective of risk factors or symptoms, is concomitant with the development of advanced atherosclerosis. Coronary thrombosis is the most common clinical end event leading to acute coronary syndrome (ACS). The least common type of pathology associated with thrombosis is the calcified nodule (CN). It usually occurs in elderly patients with severely calcified and tortuous arteries. The prevalence of calcified nodules in patients with ACS may be underestimated due to the lack of easily recognisable diagnostic methods. In this review, the authors will focus on the classification, clinical significance, pathogenesis, and diagnostic evaluation and treatment of CAC to further explore the clinical significance of CN.

Zinc-energized dynamic hydrogel accelerates bone regeneration via potentiating the coupling of angiogenesis and osteogenesis.

Insufficient initial vascularization plays a pivotal role in the ineffectiveness of bone biomaterials for treating bone defects. Consequently, enhancing the angiogenic properties of bone repair biomaterials holds immense importance in augmenting the efficacy of bone regeneration. In this context, we have successfully engineered a composite hydrogel capable of promoting vascularization in the process of bone regeneration. To achieve this, the researchers first prepared an aminated bioactive glass containing zinc ions (AZnBg), and hyaluronic acid contains aldehyde groups (HA-CHO). The composite hydrogel was formed by combining AZnBg with gelatin methacryloyl (GelMA) and HA-CHO through Schiff base bonding. This composite hydrogel has good biocompatibility. In addition, the composite hydrogel exhibited significant osteoinductive activity, promoting the activity of ALP, the formation of calcium nodules, and the expression of osteogenic genes. Notably, the hydrogel also promoted umbilical vein endothelial cell migration as well as tube formation by releasing zinc ions. The results of in vivo study demonstrated that implantation of the composite hydrogel in the bone defect of the distal femur of rats could effectively stimulate bone generation and the development of new blood vessels, thus accelerating the bone healing process. In conclusion, the combining zinc-containing bioactive glass with hydrogels can effectively promote bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

A Novel TSC2 c.2489T>C Missense Variant Associated With Tuberous Sclerosis Complex: Case Report.

Tuberous sclerosis complex (TSC) is a genetic disorder caused by a TSC1 or TSC2 gene variation characterized by widespread hamartomas in organs such as the skin, brain, heart, lungs, liver, and kidneys. We report a case of a patient with TSC who presented with broad clinical manifestations, including epilepsy. An 18-year-old man was diagnosed with recurrent drug-resistant epilepsy. Neuroimaging revealed bilateral cortical and subcortical tubers with multiple calcified subependymal nodules. His skin involvement and psychomotor retardation raised the suspicion of TSC. Genetic testing confirmed the diagnosis, and a combined treatment including mTOR inhibitors was initiated. TSC, although considered rare, needs to be considered when evaluating patients with broad clinical manifestations. Our report has significant implications for understanding the impact of genotype on the prognosis of TSC and the selection of treatment strategies for TSC-related refractory epilepsy.