Deposition Of Calcium Salts Research Articles

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Oxygen vacancy healing boosts the piezoelectricity of bone scaffolds.

Although barium titanate (BaTiO3) presented tremendous potential in achieving self-powered stimulation to accelerate bone repair, pervasive oxygen vacancies restricted the full play of its piezoelectric performance. Herein, BaTiO3-GO nanoparticles were synthesized by the in situ growth of BaTiO3 on graphene oxide (GO), and subsequently introduced into poly-L-lactic acid (PLLA) powders to prepare PLLA/BaTiO3-GO scaffolds by laser additive manufacturing. During the synthesis process, CO and C-OH in GO would respectively undergo cleavage and dehydrogenation at high temperature to form negatively charged oxygen groups, which were expected to occupy positively charged oxygen vacancies in BaTiO3 and thereby inhibit the formation of oxygen vacancies. Moreover, GO could be partially reduced to reduced graphene oxide, which could act as a conductive phase to facilitate polarization charge transfer, thus further improving the piezoelectric performance. The results showed that the oxygen peak at the specific electron binding energy in O 1s declined from 54.4% to 14.6% and the Ti3+ peak that was positively correlated with oxygen vacancies apparently weakened for BaTiO3-GO, illustrating that the introduced GO significantly decreased the oxygen vacancy. As a consequence, the piezoelectric current of PLLA/BaTiO3-GO increased from 80 to 147.3 nA compared with that of PLLA/BaTiO3. The enhanced piezoelectric current effectively accelerated cell differentiation by upregulating alkaline phosphatase expression, calcium salt deposition and calcium influx. This work provides a novel insight for the design of self-powered stimulation scaffolds for bone regeneration.

Craniological features of the American mink in south-eastern Belarus

A series of skulls (n = 27) of the American mink (Neogale vison) from the south-east of Belarus (Gomel region, floodplain of the Sozh River) was studied. The animals were caught by different hunters in 2000–2004. The sex of individuals was not determined. When examining the skull, only the most pronounced morpho-anatomical changes that can be diagnosed confidently as deviations from the norm were taken into account. In all cases, lamellar deposition of calcium salts in the area of tentorium cerebelli osseum inside the cranial vault was detected. The growing plate length reached half of the arch height in some individuals. These traits (considerable area of bone plates; presence of a sharp spine growing in different plains) allow suggesting that the analysed growths are of pathological origin. This pathology can considerably affect the viability and physiological status of individuals as it disrupts the functioning of the central nervous system. It is difficult to identify the cause of intracranial calcifications due to the possible effect of factors of various nature. Some degree of calcification of the opisthion region of foramen magnum was found. The changes occurred in the foramen shape cannot be considered phenetic variability. In most individuals, the thinning of maxillary bone in the teeth roots area is observed. However, we believe that the identified degree of bone tissue thinning is not critical and therefore does not affect the life expectancy of individuals. Two adult individuals have swelling of the maxillary bone. In one case, an extensive bone tissue excavation was identified on the left lower jaw, which led to the loss of the canine tooth. The analysed pathomorphological change is not of traumatic nature because in case of post-traumatic osteomyelitis sequesters (separating fragments) are formed. It is necessary to further analyse the American mink skulls available at scientific collections of Belarus and to identify the degree of calcium salt deposits and their impact on the foramen magnum phenotypes. We consider it necessary to create an annotated catalogue of pathologies and anomalies of the skull of the American mink in the south-east of Belarus and adjacent territories of Ukraine, since the morphological method is essential in the diagnosis of bone tissue diseases.

Combination effect of Chinese kidney-tonifying granules and platelet-rich plasma gels on enhancing bone healing in rat models with femur defects

BackgroundThe traditional Chinese kidney-tonifying granules, known as Bushen Zhongyao Keli (BSZYKL), have been found to stimulate calcium salt deposition, enhance bone formation, and foster bone growth within the bone matrix at sites of bone defects. On the other hand, platelet-rich plasma (PRP) is enriched with various growth factors capable of facilitating the repair of bone defects and enhancing bone strength following fractures. This study is dedicated to investigating the combined efficacy of BSZYKL and PRP gel (PRP-G) in the treatment of bone defects.MethodsWe established a femur defect model in male Sprague-Dawley (SD) rats and filled the defect areas with autologous coccygeal bone and PRP-G. For 8 consecutive weeks, those rats were given with intragastric administration of BSZYKL. Biomechanical characteristics of the femur were assessed 28 days after intramuscular administration. On day 56, bone formation was examined using X-ray, micro-CT, and transmission electron microscopy. Additionally, we analyzed the expression of bone formation markers, Runx2 and Osterix, in femur tissues through qPCR, Western blotting, and immunohistochemistry.ResultsRats receiving the combined treatment of BSZYKL and PRP-G exhibited drastically enhanced femoral peak torsion, failure angle, energy absorption capacity, and torsional stiffness as compared to control group. This combination therapy also led to marked improvements in bone volume, mass, and microarchitecture, accompanied by elevated expressions of Runx2 and Osterix when compared to control group. Notably, the synergistic effects of BSZYKL and PRP-G in treating bone defects surpassed the effects of either treatment alone.ConclusionsThese findings revealed the potential of BSZYKL in combination with PRP-G in improving bone defects.

ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi.

This study aims to investigate the impact of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) on vascular calcification in rats. The rationale behind studying ENPP1's role in vascular calcification lies in its potential to modulate calcification processes. Understanding this relationship can offer insights into novel therapeutic avenues for addressing vascular calcification-related disorders. In this experiment, vascular smooth muscle cell (VSMC) calcification was induced using β-glycerophosphoric acid. Subsequently, recombinant AAV9-carrying ENPP1 was introduced into VSMCs to achieve both in vitro and in vivo overexpression of ENPP1. The findings indicate that ENPP1 overexpression significantly reduces calcium and phosphorus content in the aorta (P < 0.05). Alizarin red and von Kossa staining reveal notable reductions in calcium salt deposits in VSMCs and aorta, respectively. Notably, the expression levels of BMP-2, PINP, OC, and BALP were substantially decreased in VSMCs (P < 0.05), underscoring ENPP1's role in impeding osteoblast-like transdifferentiation of VSMCs. Additionally, ENPP1 overexpression led to a significant increase in pyrophosphate (PPi) levels compared to control rats (P < 0.05). In conclusion, this study suggests that ENPP1 contributes to alleviating vascular calcification by elevating PPi levels and inhibiting the phenotypic transformation of VSMCs. These findings shed light on the potential therapeutic role of ENPP1 in mitigating vascular calcification-related complications.

Low-Intensity Nanosecond Pulsed Electric Field Accelerates Osteogenic Transformation of Human Dermal Fibroblasts by Enhancing Cell Pluripotency.

Autologous human fibroblasts have the potential to differentiate into the osteogenic lineage under specific conditions and can be utilized for bone regeneration. However, their efficiency is currently unsatisfactory. Recently, low-intensity nanosecond pulsed electric field (nsPEF) stimulation has been demonstrated to enhance cell pluripotency by activating epigenetic regulatory pathways. In this study, human dermal fibroblasts were exposed to different intensities of nsPEF to assess whether these exposures resulted in changes in proliferation rate, calcium salt deposition, and expression of differentiation-related markers in different experimental groups. The results showed a significant increase in cell proliferation, pluripotency, bone marker expression, and osteogenic differentiation efficiency when stimulating cells with 5 kV/cm of nsPEF. However, cell proliferation and differentiation significantly decreased at 25 kV/cm. Additionally, the proliferation and efficiency of osteogenic differentiation were reduced when the nsPEF intensity was increased to 50 kV/cm. Treatment with a 5 kV/cm of nsPEF led to increased and concentrated expression of Yes-Associated Protein (YAP) in the nucleus. These observations suggest that human dermal fibroblasts possess a heightened potential to differentiate into osteogenic cells when activated with nsPEF at 5 kV/cm. Consequently, the nsPEF strengthening strategy shows promise for fibroblast-based tissue-engineered bone repair research.

Nocardia seriolae mediates granulomatous chronic inflammation of spleen in Micropterus salmoides through necroptosis

Granulomatous chronic inflammation is a typical pathological characteristic of largemouth bass (Micropterus salmoides) infected by Nocardia seriolae, and it is also an important breakthrough to solve the problem of pathogen prevention and treatment.Spleen, the target organ of N. seriolae infection, is significant for studying pathogenic mechanism. However, histopathological characteristics and immunological molecular mechanisms of the development of splenic granulomas in fish have not been extensively studied. In the initial process of exploring the molecular mechanism of N. seriolae infectious splenic granuloma formation, we accidentally found positive signals of necroptosis-related gene by immunohistochemical staining, suggesting that necroptosis may be involved in the formation of granulomas.Nevertheless, the role of necroptosis in the formation of splenic granuloma is still unclear. In this study, we established a granuloma model in the spleen of largemouth bass infected by N. seriolae. Through multiple tissue staining, we compared splenic granulomas with hepatic and renal granulomas, and preliminarily clarified the histopathological characteristics of splenic granulomas and the formation pattern of fibrosis, calcium salt deposition and other lesions. Notably, we found that the expression of inflammatory factors and necroptosis-related molecules in spleen were significantly upregulated during N. seriolae infection. Further immunohistochemical staining showed that the splenic granulomas were accompanied by extensive and intense p-MLKL-positive signals in the peripheral tissue. In addition, western blot and immunofluorescence results showed that N. seriolae could induce necroptosis in primary spleen cells of largemouth bass in vitro. Our data indicated that necroptosis is closely related to the formation of splenic granulomas in largemouth bass, and provide some ideas for the study of the formation mechanism of fish granuloma.

The pterostilbene-dihydropyrazole derivative Ptd-1 ameliorates vascular calcification by regulating inflammation

Vascular calcification is an independent risk factor for cardiovascular disease. However, there is still a lack of adequate treatment. This study aimed to examine the potential of (E)-1-(5-(2-(4-fluorobenzyloxy)Styryl)-4,6-dimethoxyphenyl)-3-methyl-4,5-dihydro-1H-pyrazole-1-yl) ethyl ketone (Ptd-1) to alleviate vascular calcification. ApoE-deficient mice were fed a high-fat diet for 12/16 weeks to induce intimal calcification, and wild-type mice were induced with a combination of nicotine and vitamin D3 to induce medial calcification. Human aortic smooth muscle cells (HASMCs) and aortic osteogenic differentiation were induced in vitro with phosphate. In the mouse model of atherosclerosis, Ptd-1 significantly ameliorated the progression of atherosclerosis and intimal calcification, and there were significant reductions in lipid deposition and calcium salt deposition in the aorta and aortic root. In addition, Ptd-1 significantly improved medial calcification in vivo and osteogenic differentiation in vitro. Mechanistically, Ptd-1 reduced the levels of the inflammatory factors IL-1β, TNFα and IL-6 in vivo and in vitro. Furthermore, we demonstrated that Ptd-1 could attenuate the expression of p-ERK1/2 and β-catenin, and that the levels of inflammatory factors were elevated in the presence of ERK1/2 and β-catenin agonists. Interestingly, we determined that activation of the ERK1/2 pathway promoted β-catenin expression, which further regulated the IL-6/STAT3 signaling pathway. Ptd-1 blocked ERK1/2 signaling, leading to decreased expression of inflammatory factors, which in turn improved vascular calcification. Taken together, our study reveals that Ptd-1 ameliorates vascular calcification by regulating the production of inflammatory factors, providing new ideas for the treatment of vascular calcification.

Calcinosis cutánea en un perro con hipercortisolismo: Reporte de caso

Cutaneous calcinosis in dogs is a dermatological condition that involves the deposition of calcium salts in the animals' skin. Its etiology has not yet been fully established, but it is believed that genetic, nutritional and metabolic factors may play an important role in the development of the disease. It is divided into four subtypes, according to its pathogenesis: dystrophic; metastatic; idiopathic and iatrogenic, with dystrophic being the most common. Hypercortisolism, also known as Cushing's syndrome, is one of the main causes of cutaneous calcinosis in dogs. In this condition, there is excessive production of cortisol by the adrenal glands, leading to a series of metabolic, immune and inflammatory changes that contribute to the formation of calcium deposits in the skin. Symptoms can vary, but they usually manifest as the formation of hard, white subcutaneous nodules that may ulcerate or leak creamy material. Diagnosis is performed through clinical and laboratory examinations, such as cytology of the nodules, biopsy, and laboratory tests. Treatment aims to control the underlying disease and provide local care, but it is quite challenging as there is no specific established therapy. This study aimed to report the case of a dog diagnosed with hypercortisolism, presenting secondary cutaneous calcinosis.

The effects of Gli1 and Gli2 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Diseases, such as bone nonunion with bone defects, osteoporosis, etc, seriously endanger people's quality of life, and bone tissue engineering based on mesenchymal stem cells is an effective method to solve such problems. Several studies have shown that BMP9 can effectively promote osteogenic differentiation of MSCs, but the underlying molecular mechanisms are still unclear. Gli1 and Gli2 were important transcription factors and play an important role in the Hedgehog signaling pathway. In this study, we investigated the role of Gli1 and Gli2 in BMP9-induced osteogenic differentiation of MSCs. We found that inhibition of Gli1 and Gli2 weakened BMP9-induced osteogenic differentiation of MSCs, and early osteogenic markers (alkaline phosphatase, ALP), late osteogenic markers (calcium salt deposition), the expression of pivotal osteogenic markers were attenuated, and inhibition of Gli1 and Gli2 weakened the expression of p-Smad1/5/8 and p-p38 induced by BMP9. In conclusion, our study shows that Gli1 and Gli2 play an important role in BMP9-induced osteogenic differentiation.

Hydroxycitric acid inhibits kidney stone through crystallization regulation and reduction of hyperoxalate-induced lipotoxicity

Kidney stone is a urinary system disease with a high incidence, and effective stone drugs are limited. Hydroxycitric acid (HCA), mainly found in Garcinia cambogia and Hibiscus sabdariffa, can reduce body weight and calcium salt deposition. In this study, we explored the molecular mechanisms of HCA inhibition of renal calcium oxalate (CaOx) deposition and nephrotoxicity in an oxalate-induced cell model and rat model. HCA could effectively inhibit CaOx crystal deposition and reduce crystal adhesion and oxidative damage. Further cellular transcriptomic analysis and in vitro results showed that HCA could stably bind peroxisome proliferator-activated receptor α (PPARα), thus promoting the expression of downstream oxidative stress molecules and inhibiting calcium ion release and mitochondrial dysfunction, thus reducing oxalate-induced renal lipid peroxidation damage. HCA, a drug with the ability to modulate lipid metabolism and inhibit CaOx formation, may be a therapeutic option for the treatment of oxalate nephropathies.

Particularities of Cerebrovascular Changes in Patients with Dementia during Alzheimer’s Disease in Comparison with Distal Cerebral Atherosclerosis

AbstractBackgroundWhen studying the causes of dementia, there are certain difficulties in differentiating existing cerebrovascular changes. We present the features of cerebrovascular changes in Alzheimer’s disease (AD) and in distal forms of cerebral atherosclerosis.MethodsThe research included 935 patients, of whom: 93 people aged 34‐80 (mean age 67.5), 32 men (34.40%), 61 women (65.59%), suffered from AD. According to their dementia severity, the patients were subdivided: (TDR‐0) ‐ 10, (TDR‐1) ‐ 29, (TDR‐2) ‐ 36, (TDR‐3) ‐ 18;• 842 people aged 29‐81 (mean age 74.5), 622 men (73.87%), 220 women (26.13%), with distal cerebral atherosclerosis and chronic cerebrovascular insufficiency. According to their dementia severity, the patients were subdivided: (CDR‐1) ‐ 284, (CDR‐2) ‐ 18.• The examination plan included cerebral MRI, CT, scitrigraphy (SG), rheoencephalography (REG), cerebral multi‐gated angiography (MUGA).ResultsIn patients with AD, changes in angioarchitectonics and microcirculation are manifested in:• Absence of calcium salts deposits and atherosclerotic changes in intracerebral arteries;• Increased tortuosity of the distal parts of the intracerebral arteries;• Reduction of the capillary bed in the temporal and frontoparietal regions;• Development of multiple large arteriovenous shunts with early venous discharge of arterialblood in the same regions;• Development of abnormal venous trunks in the same regions;• Development of intracerebral stagnation of venous blood;These changes are called “Dyscirculatory angiopathy of Alzheimer’s type” (DAAT).In patients with distal cerebral atherosclerosis, changes in angioarchitectonics and microcirculation are manifested in:• Multiple calcium salts deposition and atherosclerotic changes in the intracerebral arteries;• Multiple disseminated contraction of the intracerebral capillary bed;• Development of multiple small disseminated intracerebral arteriovenous shunts;• Lack of pronounced intracerebral venous congestion.ConclusionsDyscirculatory angiopathy of Alzheimer’s type (DAAT), regardless of the severity of dementia, is an AD‐specific cerebrovascular and microcirculatory lesion of the brain not associated with atherosclerotic processes.In patients with distal cerebral atherosclerosis, regardless of the severity of dementia, vascular disorders are of disseminated atherosclerotic character. Anatomically, the lesion of the capillary bed and the presence of arteriovenous shunts are of disseminated character, and there is no pronounced venous stasis. Timely detection of these changes is very important for diagnosis.

Iatrogenic Rhinolith: A Case Report and Review of Literature.

Unilateral nasal obstruction is a common complaint with a broad differential diagnosis that includes anatomic asymmetry, unilateral infective or inflammatory conditions, and benign and malignant sinonasal masses. A rhinolith is an uncommon foreign body in the nose, which serves as a nidus for calcium salt deposition. The foreign body can be endogenous or exogenous in origin and may remain asymptomatic for many years before incidental discovery. When left untreated, stones may cause unilateral nasal obstruction, rhinorrhea, nasal discharge, epistaxis or, in rare cases, progressive destruction leading to septal/palatal perforation or oro-antral fistula. Surgical removal is an effective intervention with limited complications reported. This article describes a 34-year-old male who presented to the emergency department (ED) with unilateral obstructing nasal mass and epistaxis, which was found to be an iatrogenic rhinolith. Successful surgical removal was performed. Epistaxis and nasal obstruction are common presentations to the ED. Rhinolith is an uncommon clinical etiology that if left undiagnosed may lead to progressive destructive disease; it should be included in the differential for any unilateral nasal symptoms of unclear origin. Appropriate work-up for any suspected rhinolith includes computed tomography, as biopsy is risky given the broad differential of unilateral nasal mass. When identified, surgical removal has a high success rate with limited complications reported.

P481 PREDICTIVE FACTORS OF CLINICAL OUTCOME IN PATIENTS WITH AORTIC STENOSIS: DATA FROM THE VENETO REGISTER

Abstract Background Aortic valve stenosis represents the most relevant valve disease in the Western world, with a mortality rate exceeding 50%. Calcific aortic valve stenosis was once considered a passive process of the valve deposition of calcium salts, but is now considered a cell–mediated disease. The aim of the present study is to search for predictors of mortality, cardiovascular events and valve replacement in patients with aortic stenosis. Materials and Methods A subgroup of 140 patients affected by moderate–severe aortic valve stenosis from the Cardiology departments of the Treviso Hospital and the High Specialization Hospital of Motta di Livenza included in the Veneto Register. For each patient, information relating to deaths, cardiovascular events and valve staging was therefore collected over time. Results The deceased were 36% of which 22.9% without having replaced the valve. The mean follow–up was 24.99±21.72 months. In the follow–up, the deceased were characterized by an older age, a greater frequency of ischemic heart disease, atrial fibrillation and chronic kidney disease (CKD), a worse eGFR, a higher phosphate level. Among the Cox regression biohumoral data, serum phosphate was significantly associated with mortality in the univariate survey, and eGFR values were also always independently significantly associated with mortality. Kaplan Meyer curves also showed significant differences in the risk of CV events over time between groups with eGFR values greater than equal and less than 60 mL/min. Conclusions The results of the study suggest that the pathology appears to be linked to senescence processes and shares a common basis with atherosclerotic pathology, but also appears to be influenced in its evolution by further determinants such as CKD and blood phosphorus values. These considerations prompt us to reflect on the need for studies aimed at understanding the pathogenetic mechanisms of the proven relationship between cardiovascular MACE and phosphorus values, and that between worse renal function and cardiovascular mortality/morbidity. On the other hand, it seems urgent to be able to propose in the near future an internationally shared prognostic score that considers these predictive variables and can help us to better stratify the clinical evolution of aortic stenosis and influencing the surgical timing.

Calcinosis Cutis and Calciphylaxis Mimicking Skin Infection

Abstract Calcinosis cutis refers to the deposition of calcium salts into the skin or subcutaneous tissue, and when these calcium deposits involve the vasculature, it is known as calciphylaxis (http://www.ncbi.nlm.nih.gov/books/NBK448127/). These conditions can both mimic and predispose patients to infections; thus, diagnoses may be confused between the two. We present 3 cases involving cutaneous wounds due to calcium deposition and discuss their infectious considerations. The first case is a 74-year-old male patient with myeloid sarcoma and B-cell acute lymphoblastic leukemia who was evaluated for calciphylaxis of the bilateral lower extremities. The second case is a 70-year-old female patient with a history of squamous cell carcinoma with subsequent surgical resection and radiation therapy of the right elbow who presented with right elbow cellulitis. The third case is a 68-year-old male patient with a history of myositis ossificans and multiple surgical excisions of calcium deposits who presented with a draining wound of the left upper extremity.

The submandibular sialolithiasis in an eight-year-old child: a case report

Sialolithiasis is a commonly encountered disease of the salivary glands and represents up to 30-50% of all salivary gland diseases. However, the condition is rarely encountered in the paediatric population. The formation of a salivary stone is believed to be secondary to the deposition of calcium salts around a nidus, which is commonly associated with desquamated epithelial tissue or sloughing from a recent bacterial infection. Patients with submandibular sialolithiasis usually present with acute swelling over the neck associated with pain, fever, and purulent intraoral discharge. The calculi were located on the right in 100.0% of paediatric patients. Moreover, 20.0% of paediatric patients exhibited sialoliths in the glands. In this paper, we present the case of an 8-year-old male child who presented with a history of swelling over the right submandibular region since four months and had not responded to the conservative treatment given for the last four months. On examination, a small, rounded salivary calculus was found at the Wharton duct orifice near the papilla. A minimally invasive surgical procedure of intraoral excision of the calculus was done, and the patient was prevented from undergoing surgical excision of the gland. A large number of relatively small and distal sialoliths in paediatric patients can be removed using intraoral retrieval under local or general anesthesia. The clinical evaluation of the entire salivary tract with a high index of suspicion helps in early diagnosis and avoids the development of an abscess and other complications that may require surgical excision of the gland.

Bone Marrow Mesenchymal Stem Cells Derived from Juvenile Macaques Reversed the Serum Protein Expression Profile in Aged Macaques.

The aim of the study was to reveal the changes in serum protein composition and content in macaques during the process of ageing, and explore the effect of bone marrow mesenchymal stem cell (BMMSC) on the serum protein expression profile in elderly macaques. Naturally ageing macaques were assessed according to age. BMMSCs were intravenously infused into aged macaques. In addition, peripheral blood was collected to obtain serum for dataindependent acquisition (DIA) protein sequencing to identify aging-related indicators. One hundred eighty days after macaques received BMMSC treatment, haemoxylin and eosin (HE) staining was performed to observe the morphology and structure of aortic arches. Compared to infant and young control macaques, aged macaques showed erythema on the face, dry skin, reduced amounts of hair on the head and back, and paleness. Cultured BMMSCs from the 4th passage (P4 BMMSCs) were grown in accordance with standards used to culture mesenchymal stem cells. After BMMSC treatment, the assessed aortic arches showed no calcium salt deposition or cell necrosis, and the characteristics of the serum protein expression profile tended to be similar to that of the infant and young groups, with the expression of 41 proteins upregulated with age and that of 30 proteins downregulated with age but upregulated after BMMSC treatment. Moreover, we identified 44 significantly differentially expressed proteins between the aged model and treatment groups; 11 of the upregulated proteins were related to vascular ageing, neuronal ageing and haematopoiesis, and 33 of the downregulated proteins were associated with neuronal ageing, cardiovascular disease, and tumours. Interestingly, S100 expression in serum was significantly decreased, COMP expression was significantly increased, NKAP expression reappeared, and LCN2, CSF1R, CORO1C, CSTB and RSU-1 expression disappeared after BMMSC treatment. BMMSCs can reverse ageing-related serum protein expression.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulatedin calcific areas. We further demonstrated TCF21 expression wasincreased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Tumoral Calcinosis in the Larynx.

Tumoral calcinosis is a rare benign disease defined as calcium salt deposits in the periarticular soft tissue region. Tumoral calcinosis is rare in the neck and larynx. In this case, we described a 58-year-old man who had numerous calcified nodules in the larynx.

Calcinosis in juvenile dermatomyositis: Updates on pathogenesis and treatment.

Calcinosis, or the deposition of insoluble calcium salts in the skin, subcutaneous tissue, fascia, tendons, and muscles, is a feared complication of juvenile dermatomyositis. Calcinosis is estimated to affect up to 40% of patients with juvenile dermatomyositis and contributes to significant disease morbidity. Calcinosis can be challenging to treat, and the most effective treatment remains unknown because of a lack of comparative studies. We aim to review the literature published in the last 5 years to summarize updates on the pathogenesis and treatment of calcinosis in juvenile dermatomyositis and describe future areas for research.