Carboxyterminal Propeptide Of Type Research Articles

Permanent Pacemaker Implantation: Early Post-Implantation Data

Abstract Introduction: Data on the development of left ventricular dysfunction after permanent pacemaker implantation are available. Myocardial collagen deposition is a well-known mechanism that occurs in left ventricular remodelling. This gave us reason to dynamically monitor the levels of the main molecules involved in collagen synthesis, PIPC (carboxy-terminal propeptide of type I procollagen) and PIIINP (amino-terminal propeptide of type III procollagen). Materials and Methods: PIPC and PIIINP levels were studied using enzyme-linked immunoassays in plasma from 45 patients (25 men, 20 women, 72.1 ± 9 years) and 46 controls (24 men, 22 women, 71.9 ± 8.7 years) without known cardiovascular diseases (except arterial hypertension, conduction disorder, indication for the procedure) at baseline (immediately before PPM implantation for patients), at 12 and 24 weeks. Results: There was no difference in baseline levels of PICP and PIIINP between patients and controls (p > 0.05, Table abstract). At week 12, PICP levels increased significantly in patients compared to baseline in controls (p < 0.05, Table abstract). At week 24, values continued to increase and were again significantly higher than baseline in the controls (p < 0.001, Table abstract). At the 12-week follow-up visit, PIIINP values in patients were significantly higher than those at baseline in controls (p < 0.001, Table abstract). At week 24, the values of the patients were still higher than those of the controls, but the difference was not significant (p > 0.05, Table abstract). Conclusion: This study showed early activation of collagen synthesis < 6 months after PPM (permanent pacemaker) implantation. Due to the selection of patients without concomitant cardiovascular pathology, we have reason to assume that it is a result of the procedure itself and a serious prerequisite for increased collagen deposition in the myocardium.

Investigation of the Clinical Effect of New Shoulder Joint Abduction Frame in Humeral Fracture Patients after Arthroscopic Shoulder Surgery.

Objective This work is organized to analyze the clinical effects of new shoulder joint abduction frame on the bone metabolic markers, shoulder joint function, and visual analogue scale (VAS) of humeral fracture patients undergoing arthroscopic surgery. Methods 118 patients with humeral fracture who planned to undergo shoulder surgery in our hospital from November 2018 to June 2021 were selected as the study objects and were divided into two groups according to the random number method, with 59 patients in each group. The patients in the two groups were subjected to arthroscopic shoulder surgery. New shoulder joint abduction frame was used for shoulder joint fixation in the abduction frame group, and sling was used for shoulder joint fixation in the sling group after surgery. The duration of fixation was 4-6 weeks. Finally, the prognostic indicators, complications, and serum bone metabolism levels in 4 and 6 weeks after surgery, shoulder joint function (Neer score), VAS score before surgery and after 3 and 6 months of surgery, and excellent or good rate of shoulder joint activity after 6 months of surgery were compared between the two groups. Results The postoperative fracture healing time and start time of shoulder joint training were shorter, and the humeral varus angle and femur height loss were smaller in the abduction frame group than in the sling group (P < 0.05). There was no significant difference in the total incidence of complications between the two groups (3.39% and 13.56%, respectively) (P > 0.05). After 4 or 6 weeks of surgery, the levels of serum osteoprotegerin (OPG) and carboxyterminal propeptide of type I procollagen (PICP) were increased but the levels of tartrate-resistant acid phosphatase-5B (TRAP-5B) were decreased in the two groups with more significant differences in the abduction frame group (P < 0.05). After 6 months of follow-up, 2 cases were lost to follow-up in the abduction frame group and 3 cases in the sling group. Neer scores were increased, while VAS scores were decreased in the two groups in the third or sixth months after surgery with significant differences in the abduction frame group (P < 0.05). The excellent or good rate of shoulder joint activity was 94.74% (54/57) in the abduction frame group, significantly higher than that in the sling group (80.36%; 45/56) (P < 0.05). Conclusion The fixation effect of new shoulder joint abduction frame is significant after arthroscopic surgery, and patients can carry out functional training as early as possible, which is helpful to promote fracture healing, relieve pain, and restore shoulder joint function with high safety.

Left ventricular function is related with amphiregulin and fibrosis markers in cirrhotic cardiomyopathy.

The relationship between left ventricle (LV), extracellular matrix remodeling and fibrosis-linked amphiregulin (ARG) in cirrhotic cardiomyopathy (CCM) is unknown. The aim of the study was to investigate the associations between markers of extracellular matrix remodeling and ARG in cirrhosis and their association with indicators of ventricular remodeling and LV functional parameters. In hepatitis C virus (HCV) patients with cirrhosis, who underwent echocardiography, the presence of left ventricular diastolic dysfunction (LVDD) was determined by having gradable diastolic dysfunction in accordance with modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. A total of 87 cirrhotic patients were consecutively analyzed. Based on detailed echocardiographic assessment - 35 HCV patients with cirrhosis had normal left ventricular diastolic function (non-CCM group), whereas 52 patients had LVDD (CCM group). ARG was measured by enzyme-linked immunosorbent assay. The ARG levels were significantly increased in the CCM group compared to the non-CCM group (P<0.001). ARG levels in all HCV patients were independently associated to the presence of CCM, and showed significant correlations with LVDD. The close relationship between ARG levels and the direct serum marker of fibrosis, and selected markers of extracellular matrix (i.e. transforming growth factor-beta1 (TGF-β1), and carboxyterminal propeptide of type I collagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix proteinase-1 (TIMP-1), respectively), ventricular remodeling (i.e. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-T (hs-TnT)), and LV functional parameters suggest an active role in the myocardial injury. Using ROC analysis, the best marker for the diagnosis of CCM was NT-proBNP with AUROC = 0.796. The area under the curve of ARG (AUROC = 0.709) for predicting CCM was greater than this for PICP (AUROC = 0.662) and similar to this hs-TnT (AUROC = 0.753). The simultaneous monitoring of serum ARG and markers of extracellular matrix and ventricular remodeling can be helpful for the alterations in myocardial function control in HCV patients with cirrhosis.

Serum microRNAs and antifibrotic response to eplerenone in acute myocardial infarction complicated by systolic dysfunction

BackgroundAfter myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear. MethodsA set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied. ResultsFrom the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to −0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes. ConclusionAlthough serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.

Effect of Vitamin K2 Alone or in Combination on Various Bone Turnover Markers Amongst Postmenopausal Females.

BackgroundOsteoporosis is common in postmenopausal women. Some studies have demonstrated the usefulness of vitamin K through the action of bone-specific proteins and osteoblast and osteoclast activities. However, no systematic review had explored this aspect in postmenopausal women. Hence, this systematic review aimed to explore the effect of vitamin K2 alone or in combination with other agents (vitamin D3 or calcium) on various bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women.MethodsMEDLINE, ScienceDirect, PubMed, and Google Scholar were searched to identify relevant studies using specific inclusion criteria. Data extraction and quality assessment were carried out using standardized tests, and the results were narratively synthesized and presented in the form of tables.ResultsVitamin K2 was beneficial in inducing an improvement or preventing deterioration, as evidenced by the BMD and osteocalcin (OC), undercarboxylated OC (ucOC), carboxylated OC (cOC), and γ-carboxylated OC levels. However, its effect was not conclusive when procollagen type 1 N-terminal propeptide, carboxyterminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen, bone alkaline phosphatase, deoxypyridinoline, and N-terminal telopeptide levels (NTX) and ucOC:cOC or cOC:ucOC, and NTX:creatinine ratios were examined.ConclusionsVitamin K2 supplementation combined with vitamin D and calcium was found to be advantageous. However, vitamin K2 supplementation cannot replace the existing treatment options. In addition, vitamin K2 should be used with caution, considering its interactions with food and other drugs.

Extracellular matrix collagen biomarkers levels in patients with chronic thromboembolic pulmonary hypertension.

Limited data exist on changes in the extracellular matrix (ECM) collagen biomarkers levels during chronic thromboembolic pulmonary hypertension (CTEPH) development. This study aimed to investigate ECM collagen biomarkers levels in stable patients with CTEPH. Patients with CTEPH and healthy persons were enrolled. Serum levels of procollagen III N-terminal peptide (PIIINP), carboxyterminal propeptide of type I procollagen (PICP), matrix metalloproteinases (MMP2), MMP9, and tissue inhibitor of metalloproteinases 1(TIMP1) were measured by ELISA. Clinical data coincident with samples were collected. The pulmonary endarterectomy (PEA) and control pulmonary artery tissue samples were analyzed for genetic and immunohistochemical differences. The serum concentrations of PIIINP, PICP, MMP2, and MMP9 decreased significantly in CTEPH patients compared to healthy controls (P < 0.001 for each). CTEPH patients had higher serum concentrations of TIMP1 (median, 111.97 [interquartile range, 84.35-139.93]) compared to healthy controls (74.97 [44.03-108.45] ng/mL, P < 0.001). The MMP2 to TIMP1 ratio was lower in patients than in the controls (P < 0.001). After adjusting for the body mass index (BMI), the MMP2 to TIMP1 ratio correlated negatively with pulmonary vascular resistance (PVR) (r = - 0.327, P = 0.025). Increased TIMP1 (P = 0.04) gene expression was identified in tissues of CTEPH patients. Immunohistochemistry results of vascular walls substantiated qRT-PCR results. This study indicates that ECM collagen biomarkers levels were significantly different in stable patients with CTEPH and healthy controls with significantly increased TIMP1 and decreased MMP2 and MMP9. Differences in TIMP1 expression should be expected not only among healthy controls and patients serum, but also across pathological tissue regions. These findings suggest that the state of vascular remodeling in pulmonary vascular bed in stable patients may be represented by ECM collagen biomarkers levels. We conclude that TIMP1 may play an important role in pulmonary vascular reconstruction in stable CTEPH patients.

Role of Carboxy Terminal Propeptide of Type I and Type III Procollagen (PICP and PIIICP) Toward the Severity Degree of Mitral Valve Regurgitation in Children’s Rheumatic Heart Disease

BACKGROUND: Rheumatic heart disease (RHD) is recognized as a heart disease that occurs as a result of sequelae in acute rheumatic fever (ARF), characterized by the occurrence of defects in the heart valves. The most common manifestation of childhood RHD is mitral regurgitation (MR). The role of inflammation and oxidative stress in RHD also involves several components consisting of carboxy-terminal pro-peptide of Type I procollagen (PICP) and carboxy-terminal pro-peptide of Type III procollagen (PIIICP).&#x0D; AIM: The aim of this study was to know whether PICP and PIIICP can be used to measure the severity level of mitral valve regurgitation.&#x0D; METHODS: This research is considered as descriptive-analytic research, and using cross-sectional analysis. Forty RHD patients underwent echocardiographic examinations to measure Wilkin and effective regurgitant orifice area scores. Patients were classified into ARF without valve abnormalities, mild, moderate, and severe MR. PICP and PIIICP were with ARF through venous blood and ELISA was examined. Data were analyzed by employing SPSS 22 with p = 0.05). Wilkins scores and PICP levels have a regression coefficient of 0.296 with a p-value of 0.032.&#x0D; RESULTS: There was a significant difference in PICP level among the studied sample groups with a p = 0.012, (p &lt; 0.05), with insignificant difference in PIIICP level among sample groups with a p = 0.083, greater than α = 0.05 (p &gt; 0.05). Wilkins scores and PICP level have a regression coefficient of 0.296 with a p = 0.032 (p &lt; 0.05), while PIIICP level has a regression coefficient of 0.093 with a p = 0.568 (p &gt; 0.05).&#x0D; CONCLUSION: There is no significant increase indicated on PIIICP level, but PICP level indicates a significant increase in RHD group with severe mitral valve abnormalities. PICP can be used to measure the severity level of mitral valve regurgitation.&#x0D;

Homage Proof of Concept Trial of Spironolactone for the Prevention of Heart Failure

Introduction In patients at risk of developing heart failure (HF), targeting cardiac fibrosis might be a major determinant of slowing the progression HF. Hypothesis HOMAGE (Heart OMics in AGEing) investigated whether a 9-month exposure to spironolactone can favourably alter markers of progression to HF. Methods In this proof-of-concept, multi-centre, randomized, open-label with blinded evaluation design (PROBE) trial, we compared the effect of spironolactone 25-50 mg/day to standard care in patients aged 60 or more, at risk of developing HF (coronary artery disease and/or diabetes and/or hypertension, and NT-pro BNP 125 to 1,000 ng/L or BNP 35 to 280 ng/L, and no HF history, signs or symptoms. Patients were assessed at baseline, 1, 3 and 9 months for changes in peptides Procollagen Type III N-Terminal Peptide (PIIINP) and Carboxy-Terminal Propeptide of Type 1 Procollagen (P1CP) (primary endpoint). Secondary end-points include changes in cardiac dimensions and function, functional capacity, NTproBNP and multi-omics biomarker profiles (Olink proteomics, miRNA, MS metabolomics and transcriptomics). Whether the effect can be predicted by the baseline bioprofiles was assessed using interaction analysis. Results A total of 527 patients were randomised, 265 to spironolactone and 262 to usual care. The treatment groups were well balanced (aged 73 years, 26% female, 40% diabetes 71% history of myocardial infarction, blood pressure 140/78 mmHg, eGFR 72 ml/min, LVEF 63%, the left atrial volume (LAV) 60 ml, LV mass 180g, median PIIINP 4 (3-5) ng/mL, PICP 80 (65-97) ng/mL, and Galectin-3 16 (13-20) ng/mL. Spironolactone did not significantly affect the PIIINP levels: -0.15 (-0.44, 0.15), p=0.32 but PICP was significantly reduced by spironolactone: -8.1 (-11.9, -4.3), p=0.001, increased LVEF +1.2 (0.2, 2.2), p=0.022, reduced LAV -2.5 (-4.5, -0.6), p=0.010, and tended to reduce LVM -4.1 (-8.6, 0.4), p=0.076. Detailed analyses of the other endpoints, and of prediction of changes using baseline bioprofiles, will be presented at the time of the meeting. Conclusions In patients at risk of developing HF, mineralocorticoid receptor antagonist therapy produces changes in circulating levels of PICP and in echocardiographic parameters, potentially contributing to preventing progression to HF. Other results, including whether multi-omics bioprofiles may predict response and could help selecting patients in a future MRA HF-prevention trial will be presented. (NCT02556450, EUFP7 HOMAGE ID: 305507).

Effects of dietary calcium to available phosphorus ratios on bone metabolism and osteoclast activity of the OPG /RANK/RANKL signalling pathway in piglets.

Hydroxyapatite, a mineral form of calcium (Ca) and phosphorus (P) that gives bones their rigidity, is the major and essential component of bones and teeth in the human and animal body. A suitable ratio of Ca and P is vital for bone growth. The aim of this study was to explore the effects of dietary calcium to available phosphorus ratios (Ca/AP) on bone metabolism and osteoclast activity of the osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) signalling pathway in piglets. At days 15 and 29, the piglets were assessed for growth performance, blood indicators, cytokines and the OPG/RANK/RANKL signalling pathway. Our results showed that piglets fed a dietary Ca/AP ratio of 2:1 increases growth performance and regulates blood indicators and cytokines (parathyroid hormone (PTH), calcitonin (CT), vitamin D3 (VD3 ), insulin-like growth factor-1 (IGF-1), transforming growth factor-β (TGF-β), interleukin-1 (IL-1), interleukin-6 (IL-6), carboxyterminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRACP), alkaline phosphatase (ALP) and osteocalcin (OCN) content). We also demonstrated that this ratio affects hormone secretion and further bone metabolism through the OPG/RANK/RANKL signalling pathway of osteoclasts. These results indicate that a suitable dietary Ca/AP ratio is vital for bone growth and reduce the incidence of bone diseases such as osteoporosis, providing a practical basis for the raising of piglets.

The effects of fascia manipulation with fascia devices on myofascial tissue, subcutaneous fat and cellulite in adult women

Objectives: The purpose of this study was to investigate the effects of mechanical fascia manipulation techniques as a noninvasive method to treat cellulite.Study Design: This study is designed to be a clinical study looking at the effects of a non-invasive treatment for the appearance of cellulite. Methods: Thirty-three adult women in the experimental (FT) group with thigh cellulite were instructed on fascia manipulation techniques (FMT), using the FasciaBlaster® devices (FBD) 5 days a week for 12 weeks. Measurements of subcutaneous adipose thickness (SAT) were measured using ultrasonography, along with measurements of body composition, metabolism, and routine blood chemistries at 4-week intervals.Results: In the FT group, SAT was lower from baseline at Wk4, Wk8, and Wk12. Resting energy expenditure (REE) was greater at Wk12 compared to baseline. Carboxyterminal Propeptide of Type I Procollagen (PICP) was higher at Wk4 compared to baseline. Also compared to baseline, serum irisin levels were significantly higher at Wk4, Wk8, and Wk12. No significant differences were detected in routine blood chemistries or total body composition during study period in both the FT group and the control group (CON).Conclusions: The present study provides evidence that fascia manipulation techniques (FMT), through use of the FasciaBlaster® devices (FBD), can decrease subcutaneous adipose tissue (SAT), and the appearance of cellulite in adult women over 12 weeks. Evidence also shows improved collagen remodeling and the overall safety of fascia manipulation and the FasciaBlaster® devices.

A18883 New Insights in Rheumatic Heart Disease- role of circulating carboxy-terminal propeptide of type I procollagen (PICP)

A18883 New Insights in Rheumatic Heart Disease- role of circulating carboxy-terminal propeptide of type I procollagen (PICP)

Calcium gluconate alleviates the toxic effect of hydrofluoric acid on human dermal fibroblasts through the Wnt/β-catenin pathway.

The present study was performed to determine the molecular mechanism of calcium gluconate (CG) in alleviating the toxic effect of hydrofluoric (HF) acid on human dermal fibroblasts (HDFs). HDF morphology was observed by optical microscopy and the vimentin immunofluorescence assay. Cell viability and apoptosis were evaluated by the Cell Counting Kit-8 and Annexin V/propidium iodide assays, respectively. The levels of apoptosis-associated factors, as well as Wnt2, Wnt3a and β-catenin were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. Levels of matrix metalloproteinase (MMP)-1 and basic fibroblast growth factor (bFGF) were detected by ELISA and western blotting. Carboxyterminal propeptide of type I collagen (CICP) was detected by ELISA, while L-Hydroxyproline (L-HYP) was detected by colorimetry. First, the morphology of normal HDFs was observed. Cell viability was inhibited and apoptosis was increased in a dose- and time-dependent manner following treatment with HF acid [0, 2, 4, 6, 8, 10 and 20% (v/v)] for 0, 2, 4, 6, 8, 10 and 20 min. The effects were blocked by CG at different doses (50, 100 and 200 µmol/l) and time points (6, 12 and 24 h), following treatment with 8% (v/v) HF acid for 6 min. The levels of Caspase-3, B-cell lymphoma (Bcl)-2 associated X protein, Wnt2, Wnt3a and β-catenin were decreased, whereas Bcl-2 was increased by CG treatment dose-dependently, when compared with HF control. CG promoted the expression of MMP-1, bFGF and L-HYP, and inhibited CICP, when compared with HF control. Based on the present results, CG alleviated the toxic effect of HF acid on HDFs by regulating the Wnt/β-catenin signaling pathway.

The novel diagnostic marker in low-LVEF heart failure patients.

The structural and compositional changes in the myocardium seem to have a major role in the development of heart failure (HF).Imbalance between production and degradation in extracellular collagen results in increase of collagen synthesis biomarkers in the circulation as the carboxy-terminal propeptide of type I procollagen (PIP). Here we aimed to determine role of PIP in the diagnosis of chronic HF. 87 patients with HF group and 80 healthy subjects were enrolled into the study. Echocardiographic examination was performed.At the beginning of the study, serum B type natriuretic peptide (BNP), PIP, high sensitive C-reactive protein (hs-CRP) were measured . The subjects were followed for one year then after. Average PIP value of HF group was significantly higher than that of the control group (p < 0.001). Both hs-CRP and BNP values were well correlated to PIP values (p < 0.001). In the HF group, PIP value of patients who died at the end of one year was similar to that of patients who survived at the end of first year. PIP may not mirror acute events in follow-up of chronic heart failure but it is a very beneficial biomarker in diagnosis of low-LVEF heart failure with high sensitivity and specificity (Tab. 2, Fig. 1, Ref. 16).

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.

Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3',5'-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre- and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3',5'-cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis. Chemical compounds studied in this article Udenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634). Impact statement The results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance.

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and carboxyterminal cross-linked telepeptide of type I collagen in malignant tumor patients with bone metastasis

OBJECTIVETo investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal cross-linked telepeptide of type I collagen (ICTP), in cancer patients with bone metastasis. METHODSPatients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTSA significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSIONYishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs), and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis

Objectives: To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA).Method: Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay.Results: No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women.Conclusions: Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF–IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.

No evidence of adverse cardiac remodeling in former elite endurance athletes

BackgroundThe impact of high exercise loads on a previously healthy heart remains controversial. We examined the consequences of decades of strenuous endurance exercise at the highest competition level on heart dimensions and volumes as well as on serum biomarkers of cardiac fibrosis/remodeling. Methods and resultsWe compared echocardiographic measurements and serum biomarkers of cardiac fibrosis/remodeling [troponin I, galectin-3, matrix metallopeptidase-2 and -9, N-terminal pro-brain natriuretic peptide, carboxy-terminal propeptide of type I procollagen, and soluble suppressor of tumorigenicity-2 (sST-2)/interleukin(IL)-1R4] in 53 male athletes [11 former professional (‘elite’) and 42 amateur-level (‘sub-elite’) cyclists or runners, aged 40–70years] and 18 aged-matched controls. A subset of 15 subjects (5 controls, 3 sub-elite and 7 elite athletes) also underwent cardiac magnetic resonance imaging (cMRI).Elite and sub-elite athletes had greater echocardiography-determined left ventricular myocardial mass indexed to body surface area than controls (113±22, 115.2±23.1 and 94.8±21g/m2, respectively, p=0.008 for group effect), with similar results for left (50.5±4.4, 48.2±4.3 and 46.4±5.2mm, p=0.008) and right (38.6±3.8, 41.1±5.5 and 34.7±4.3mm, p<0.001) ventricular end-diastolic diameter, and cMRI-determined left atrial volume indexed to body surface area (62.7±8.1, 56.4±16.0 and 39.0±14.1ml/m2, p=0.026). Two athletes showed a non-coronary pattern of small, fibrotic left ventricular patches detected by late gadolinium enhancement. No group effect was noted for biomarkers. ConclusionsRegardless of their competition level at a younger age, veteran endurance athletes showed an overall healthy, non-pathological pattern of cardiac remodeling. Nonetheless, the physiopathology of the ventricular fibrotic patches detected warrants further investigation.

Fragmented QRS complexes are a marker of myocardial fibrosis in hypertensive heart disease.

Carboxy-terminal propeptide of type 1 procollagen (PICP) is a marker of extracellular collagen synthesis. Fragmented QRS (fQRS) on a 12-lead electrocardiogram (ECG) has been demonstrated as a marker of myocardial fibrosis. The present objective was to investigate the association between serum PICP concentration and presence of fQRS on ECG in hypertensive patients. Consecutive patients with previously or newly diagnosed hypertension were included. fQRS was defined as the presence of additional R-wave (R'), or notching of R- or S-waves, or the presence of fragmentation in 2 contiguous ECG leads. Serum PICP levels were measured by ELISA method. The study group consisted of 90 hypertensive patients (74% females, with a mean age of 54.7±8.5 years). Of these patients, 47 (52.2%) had fQRS on ECG. Age (p=0.121) and gender distribution (p=0.625) were similar in patients with or without fQRS. Receiver operating characteristic curve analysis yielded a strong predictive ability of PICP levels for the presence of fQRS (area under the curve: 0.850; 95% CI: 0.772-0.929; p<0.0001). In multivariate logistic regression analysis, PICP levels were strongly and independently associated with the presence of fQRS (OR: 1.938; 95% CI: 1.398-2.688). Serum PICP level is a strong and independent predictor of fQRS. Discriminative performance of serum PICP levels for the presence of fQRS is high. The present results are the first to demonstrate that fQRS may indicate myocardial fibrosis in patients with hypertension.

Bone-Healing Capacity of PCL/PLGA/Duck Beak Scaffold in Critical Bone Defects in a Rabbit Model.

Bone defects are repaired using either natural or synthetic bone grafts. Poly(ϵ-caprolactone) (PCL), β-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the bone-healing capacity of PCL/PLGA/duck beak scaffold in critical bone defects and the oxidative stress status of the graft site in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: group 1 (control), group 2 (PCL/PLGA hybrid scaffolds), group 3 (PCL/PLGA/TCP hybrid scaffolds), and group 4 (PCL/PLGA/DB hybrid scaffolds). A 5 mm critical defect was induced in the diaphysis of the left radius. X-ray, micro-CT, and histological analyses were conducted at (time 0) 4, 8, and 12 weeks after implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were measured and oxidative stress status was determined. X-ray, micro-CT, biochemistry, and histological analyses revealed that the PCL/PLGA/duck beak scaffold promotes new bone formation in rabbit radius by inducing repair, suggesting that it could be a good option for the treatment of fracture.

Effects of Aluminum Exposure on the Bone Stimulatory Growth Factors in Rats.

Aluminum (Al) is considered to be a potentially toxic metal and inhibits bone formation. Transforming growth factor β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) play an important role in regulating the bone formation. Therefore, this study aimed to investigate the effects of Al on the TGF-β1 and BMP-2 in rats. In this study, Wistar rats were randomly divided into Al-treated group and control group. The Al-treated rats were provided with drinking water containing 100mg/L AlCl3, and the control rats were given distilled water for 30, 60, and 90days, respectively. Ten rats were sacrificed in each group every 30days. The Al-treated rats showed lower body weight and higher serum and bone levels of Al compared with the control rats. The expression levels of TGF-β1 and BMP-2 were also significantly decreased in the Al-treated rats. Serum levels of bone gamma-carboxyglutamic acid protein (BGP), carboxy-terminal propeptide of type I procollagen (PICP), and bone alkaline phosphatase (B-ALP) were markedly lower in the Al-treated groups than in the control group. These results indicate that Al inhibits the expression of TGF-β1 and BMP-2 in bone, which inhibits the activity of osteoblasts and reduces the synthesis of BGP, B-ALP, and type I collagen, thereby inhibiting bone formation.