Procollagen Type Research Articles

Assessment of muscle mass and bone density in elderly patients with type 2 diabetes mellitus depending on the level of glycated hemoglobin

Aim to assess the prevalence of low muscle mass and low bone density in elderly patients with type 2 diabetes (T2DM), depending on the level of glycated hemoglobin (HbA1c).
 Material and methods.The study included 187 patients (mean age 65.16 4.31 years), who were tested for fasting blood glucose, HbA1c, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), C-terminal type I collagen telopeptides (B-CTX), 25-hydroxyvitamin D, body composition and bone mineral density.
 Results.The prevalence of low muscle mass, osteopenia, and osteoporosis in elderly patients with T2DM was 35.8%, 38.5%, and 30.5%, respectively. The prevalence of low muscle mass was significantly higher in women with HbA1c 9.0% (p =0.035). Osteopenia and osteoporosis prevailed in men with HbA1c 9.0% (p=0.007 and p=0.048, respectively). The appendicular skeletal muscle index (ASMI), bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine, BMC and BMD of the thigh were significantly reduced in the osteoporosis and osteopenia groups (p0.05); while B-CTX, P1NP were significantly increased. In men, both ASMI (p=0.007) and P1NP levels (p=0.001) were important risk factors for osteopenia/osteoporosis, and in women such risk factor was ASMI (p=0.019).
 Conclusion.In T2DM patients, the high HbA1c levels were associated with higher rates of low muscle mass in women and osteoporosis in men, and ASMI was a risk factor for osteoporosis in both sexes.

Hydroxyapatite-chitosan composites derived from sea cucumbers and shrimp shells ameliorate femoral bone defects in an albino rat model.

A bone defect is defined as a critically sized autologous bone and a bone gap. Bone grafting is one of the most commonly used surgical methods to enhance bone regeneration in orthopedic procedures. A composite of collagen, hydroxyapatite (HA), and chitosan (Ch) is suitable as a bone matrix and stimulates ossification. This study aimed to evaluate the use of natural HA-Ch composites derived from sea cucumbers and shrimp shells and quantify the levels of cytokines, polymorphonuclear neutrophils (PMNs), serum liver enzymes, calcium, phosphate, and procollagen type 1 N-terminal propeptide (PINP) in albino rats with femoral bone defects. A total of 48 albino rats with femoral bone defects were divided into 4 groups (n = 12 each): (C-) placebo, (C+) polyethylene glycol, (T1) HA, and (T2) HA-Ch groups. Each group was divided into two subgroups (n = 6 each), with euthanization on 7- and 42-day post-treatment, respectively. Procollagen Type 1 N-terminal propeptide and the cytokines interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-alpha were quantified using enzyme-linked immunosorbent assay. Flow cytometry was performed to evaluate PMNs. A clinical chemistry analyzer was used to measure the serum levels of liver enzymes, calcium, and phosphate. There was a significant decrease in the level of IL-6 on 7 days and in the level of IL-10 on 42 days in the HA-Ch group. The level of PMNs also decreased significantly on 7 and 42 days in the HA-Ch group. Regarding serum liver enzymes, alkaline phosphatase (ALP) levels in the HA-Ch group increased significantly on 42 days. Calcium and phosphate levels increased significantly on 7 and 42 days in the HA and HA-Ch groups, and PINP levels increased significantly on 7 and 42 days in the HA-Ch group. The HA-Ch composite derived from sea cucumbers and shrimp shells ameliorated femoral bone defects in albino rats. The HA-Ch composite modulated the levels of IL-6, IL-10, PMNs, ALP, calcium, phosphate, and PINP on 7- and 42-day post-treatment.

A case of elevated P1NP levels: uncovering Paget's disease in a postmenopausal woman

INTRODUCTION: Procollagen type 1 N-terminal propeptide (P1NP) is a marker of bone formation that is frequently used in the diagnosis and management of osteoporosis. Elevated levels of P1NP may indicate increased bone turnover, which can be a sign of various bone disorders. Paget’s disease of bone is a chronic disorder characterized by excessive and disorganized bone remodeling. The exact cause of Paget’s disease is unknown, but it is thought to be related to genetic factors and viral infections.CASE REPORT: A 48-year-old postmenopausal woman presented with a six-month history of low back pain. Her DEXA scan showed osteopenia in the lumbar spine, and her serum P1NP level was markedly elevated. Further workup revealed a diagnosis of Paget’s disease of bone. The patient was treated with bisphosphonates, resulting in significant improvement in her symptoms and normalization of her P1NP level.CONCLUSIONS: This case highlights the importance of considering Paget’s disease as a potential cause of elevated P1NP levels. The use of bisphosphonates can be effective in treating Paget’s disease and improving bone health. Elevated P1NP levels can be seen in various bone disorders, and clinicians should be aware of its potential clinical implications. The measurement of P1NP is routinely included in the workup of patients with suspected bone disorders, and its levels are used to monitor response to treatment.

Abstract 245: Endothelin-1 And Procollagen Type-1 Carboxy-terminal Propeptide Are Associated With Functional Tolerance And Cardiac Structure And Function In Heart Failure With Preserved Ejection Fraction

Introduction: The role of emerging biomarkers such as endothelin-1 (ET-1) and collagen peptides in functional tolerance among patients with heart failure with preserved ejection fraction (HFpEF) is not well understood. Hypothesis: We hypothesize that plasma ET-1 and procollagen type-1 carboxy-terminal propeptide (PICP) are associated with 6-minute walk distance and parameters of cardiac structure and function. Methods: In a cross-sectional cohort study, we evaluated the association of ET-1 and PICP with 6-minute walk distance and parameters of cardiac structure and function on cardiac magnetic resonance (CMR) imaging in patients with HFpEF. In a subset of patients, we used a novel diffusion tensor imaging CMR technique to determine the myocardial fiber orientation in the septum as characterized by the helix angle transmurality (slope of the helix angle versus transmural depth from endocardium to epicardium) (Fig 1C). Results: A total of 36 patients (25 with HFpEF, 11 controls), mean age 70 ± 7.7 yrs, BMI 33 ± 8.5 kg/m 2 , 94% men, 53% had diabetes, and 75% had hypertension. Mean LVEF 58.7 ± 7.7%, RVEF 49.1 ± 10.4%, mean global myocardial mid- LV T1 1285ms, mean LV mass indexed to body surface area 65 ± 12 g/m 2 . Using univariate linear regression, we found that both plasma ET-1 levels and PICP levels were moderately inversely associated with 6-minute walk distance (R 2 -0.56, p<0.001) and (R 2 -0.40, p=0.02) (Fig 1A) respectively, with a non-significant association with age (R 2 = 0.30, p=0.08) and indexed LV mass (R 2 =0.29, p=0.09). ET-1 was moderately associated with septal HAT, a marker of myocardial fiber orientation, (R 2 =0.58, p=0.02), measured in a subset of patients (Fig 1B, C). Conclusions: Plasma ET1 and PICP levels are moderately associated with lower 6-minute walk distance; ET-1 is associated with septal myocardial fiber orientation in this exploratory analysis. Future studies are needed to determine the prognostic value of these biomarkers in patients with HFpEF.

Expression and diagnostic significance of integrin beta-2 in synovial fluid of patients with osteoarthritis.

Osteoarthritis (OA) is characterized by synovial cartilage degeneration and is the leading cause of disability and pain worldwide. This study sought to investigate the expression of integrin beta-2 (ITGB2) in synovial fluid of OA patients and its clinical significance. A total of 110 OA patients were enrolled, who were classified into grade I (N = 35), II (N = 42), and III (N = 33) according to the Kellgren-Lawrence classification, with 110 healthy subjects as controls, and their clinical data were compared. ITGB2 level was detected by RT-qPCR. The receiver operating characteristic curve was used to analyze the predictive value of ITGB2 on OA occurrence. The correlation between ITGB2 and bone metabolism indexes procollagen type I N-terminal peptide (PINP), bone glaprotein (BGP), bone alkaline phosphatase (BALP), and β-collagen I telopeptide (β-CTX) was analyzed by the Pearson method. Logistic regression model was performed to analyze the influencing factors of OA. The content of red blood cells, white blood cells, PINP, BGP, and BALP was lowered in OA patients, while β-CTX was elevated. ITGB2 was highly-expressed in OA patients, negatively-correlated with PINP, BGP, and BALP, but positively-correlated with β-CTX. ITGB2 level increased with the elevation of OA grade. The ITGB2 level >1.375 had certain diagnostic values for OA. ITGB2 level is related to OA severity and may be a biomarker for OA classification. ITGB2 was an independent risk factor for OA. High expression of ITGB2 in synovial fluid can assist OA diagnosis and may be a biomarker for OA grade.

Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy: The Screenshot of a Biochemical Signature.

to investigate the effects of intensive chemotherapy and glucocorticoid (GC) treatment on bone remodeling markers in children with acute lymphoblastic leukemia (ALL). A cross-sectional study was carried out in 39 ALL children (aged 7.64 ± 4.47) and 49 controls (aged 8.7 ± 4.7 years). Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (bALP), tartrate-resistant acid phosphatase 5b (TRACP5b), procollagen type I N-terminal propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Statistical analysis was conducted using the principal component analysis (PCA) to study patterns of associations in bone markers. ALL patients showed significantly higher OPG, RANKL, OC, CTX, and TRACP5b than the controls (p ≤ 0.02). Considering ALL group, we found a strong positive correlation among OC, TRACP5b, P1NP, CTX, and PTH (r = 0.43-0.69; p < 0.001); between CTX and P1NP (r = 0.5; p = 0.001); and between P1NP and TRAcP (r = 0.63; p < 0.001). The PCA revealed OC, CTX, and P1NP as the main markers explaining the variability of the ALL cohort. Children with ALL showed a signature of bone resorption. The assessment of bone biomarkers could help identify ALL individuals who are most at risk of developing bone damage and who need preventive interventions.

Association between Vitamin D, P1NP, and BMD as major indicators of bone health in local population of Pakistan

It is commonly known that the Pakistani population has inadequate vitamin D levels, but its effects on bone health and the level of N-terminal peptide of procollagen (PINP) have not yet determined. The aim of the research work was to check the vitamin D grade of exercisers and non-exercisers and examine how it related to P1NP concentration, a biochemical marker of bone production, and bone mineral density. A random sampling technique was used to select males and females who were staying in neighborhood. They were between the ages of 18 and 35 years. 92 people of Pakistani ancestry made up the total population. With 46 people, Group A was a non-exercising control group. Group B has 46 individuals in it. Both of these groups were gathered for the data analysis. BMD, procollagen type-1 amino-terminal pro-peptide, calciferol, and other biological indicator of bone remodeling were measured in serum. (P1NP). Using broadband ultrasound attenuation, the quality of the bones was evaluated. Before training, the total 25(OH)D serum were considerably less in non-exercising group than they were during or after training. (Mean: 0.4992, Standard Deviation: -1.6075; P 0001).

Ketonization of Ginsenoside C-K by Novel Recombinant 3-β-Hydroxysteroid Dehydrogenases and Effect on Human Fibroblast Cells.

The ginsenoside compound K (C-K) (which is a de-glycosylated derivative of major ginsenosides) is effective in the treatment of cancer, diabetes, inflammation, allergy, angiogenesis, aging, and has neuroprotective, and hepatoprotective than other minor ginsenosides. Thus, a lot of studies have been focused on the conversion of major ginsenosides to minor ginsenosides using glycoside hydrolases but there is no study yet published for the bioconversion of minor ginsenosides into another high pharmacological active compound. Therefore, the objective of this study to identify a new gene (besides the glycoside hydrolases) for the conversion of minor ginsenosides C-K into another highly pharmacological active compound. Lactobacillus brevis which was isolated from Kimchi has showed the ginsenoside C-K altering capabilities. From this strain, a novel potent decarboxylation gene, named HSDLb1, was isolated and expressed in Escherichia coli BL21 (DE3) using the pMAL-c5X vector system. Recombinant HSDLb1 was also characterized. The HSDLb1 consists of 774 bp (258 amino acids residues) with a predicted molecular mass of 28.64 kDa. The optimum enzyme activity was recorded at pH 6.0-8.0 and temperature 30 °C. Recombinant HSDLb1 effectively transformed the ginsenoside C-K to 12-β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3-oxo-C-K). The experimental data proved that recombinant HSDLb1 strongly ketonized the hydroxyl (-O-H) group at C-3 of C-K via the following pathway: C-K → 3-oxo-C-K. In vitro study, 3-oxo-C-K showed higher solubility than C-K, and no cytotoxicity to fibroblast cells. In addition, 3-oxo-C-K induced the inhibitory activity of ultraviolet A (UVA) against matrix metalloproteinase-1 (MMP-1) and promoted procollagen type I synthesis. Based on these expectations, we hypothesized that 3-oxo-C-K can be used in cosmetic products to block UV radiations and anti-ageing agent. Furthermore, we expect that 3-oxo-C-K will show higher efficacy than C-K for the treatment of cancer, ageing and other related diseases, for which more studies are needed.

Hemoglobin levels as a surrogate marker of sarcopenia in patients with liver cirrhosis.

This study aimed to elucidate a surrogate marker of sarcopenia in patients with liver cirrhosis (LC). A total of 424 patients were assessed for handgrip strength (HGS) and skeletal muscle index (SMI). They were divided into two groups: sarcopenia (Group S; n = 80) and nonsarcopenia (Group NS; n = 344). Group S showed significantly lower HGS, SMI, and hemoglobin (Hb) levels in males and females; and lower serum levels of albumin, cholinesterase, and zinc (all p < 0.001), along with significantly higher serum levels of procollagen Type III-N-peptide and type IV collagen 7S-domain (p < 0.001 and p < 0.0017) than Group NS. The risk factors for sarcopenia were age ≥ 65 years, female, Child-Pugh class C, and Hb levels < 10.9 g/dL in females and < 12.4 g/dL in males (p = 0.012, p < 0.001, p = 0.031 p < 0.001). Significant positive correlations were found between the Hb level and the SMI and HGS (r = 0.4 p < 0.001, r = 0.4 p < 0.001). Sarcopenia, low HGS, and low SMI were significantly associated with overall survival in patients with LC (all p < 0.001). The predictive accuracy of Hb levels for predicting sarcopenia was significantly higher than that for predicting SMI and tended to be higher than that for predicting HGS (p = 0.014 and p = 0.059, respectively). Hb levels are predictive of sarcopenia in patients with LC and warrants further investigation as a biomarker for sarcopenia in LC. This article is protected by copyright. All rights reserved.

Relationship between Body Mass Index and Bone Turnover Markers in Girls with Idiopathic Central Precocious Puberty.

This study aimed to determine the effect of body mass index (BMI) on bone turnover markers in girls with idiopathic central precocious puberty (ICPP) according to weight status at diagnosis. Two hundred and eleven girls with ICPP were divided according to their weight status at diagnosis into three groups: normal weight, overweight, and obese. The serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin, β-C-terminal telopeptide of type 1 collagen, and some biochemical indicators were measured. Associations between variables were evaluated by multiple regression analysis. Serum P1NP concentrations were significantly different among groups (p < 0.001). No other significant differences were noted in N-terminal midfragment of osteocalcin and β-C-terminal telopeptide of type 1 collagen. BMI was associated with estradiol (r = 0.155, p < 0.05) and inversely associated with P1NP (r = -0.251, p < 0.01), luteinizing hormone peak (r = -0.334, p < 0.01), follicle-stimulating hormone peak (r = -0.215, p < 0.01), and luteinizing hormone/follicle-stimulating hormone peak (r = -0.284, p < 0.01). Multiple regression analysis of factors associated with BMI showed that it was correlated with P1NP, follicle-stimulating hormone base, and luteinizing hormone peak in the overweight group and the obese group. Our findings showed that BMI was associated with P1NP, revealing the reduction of bone formation in overweight and obese girls with ICPP. During the diagnosis and treatment of girls with ICPP, attention should be paid to body weight and bone metabolism.

Targeted Deletion of Rictor in BMSCs Reduces the Biological Activity of K7M2 Cells and Mitigates OS-Induced Bone Destruction.

Bone marrow mesenchymal stem cells (BMSCs) are indispensable cells constituting the bone marrow microenvironment that are generally recognized as being involved in the development and progression of osteosarcoma (OS). To explore whether mTORC2 signaling inhibition in BMSCs suppressed OS growth and tumor-caused bone destruction, 3-month-old littermates genotyped Rictorflox/flox or Prx1-cre; Rictorflox/flox (with same gender) were injected with K7M2 cells in the proximal tibia. After 40 days, bone destruction was alleviated in Prx1-cre; Rictorflox/flox mice, as observed on X-ray and micro-CT. This was accompanied by decreased serum N-terminal propeptide of procollagen type I (PINP) levels and reduced tumor bone formation in vivo. Interactions between K7M2 and BMSCs were studied in vitro. Rictor-deficient BMSCs, which were cultured in tumor-conditioned medium (TCM), caused reduced bone proliferation and suppressed osteogenic differentiation. Moreover, compared with the control group, K7M2 cells cultured in BCM (culture medium extracted from Rictor-deficient BMSCs) displayed less proliferation, migration, and invasion, and attenuated osteogenic activity. Forty types of cytokines were then analyzed by mouse cytokine array and decreased levels CCL2/3/5 and interleukin-16 were detected in Rictor-deficient BMSCs. These results suggested that inhibition of mTORC2 (Rictor) signaling pathway in BMSCs exerted anti-OS effects through 2 mechanisms: (1) by suppressing the proliferation and osteogenic differentiation of BMSCs induced by OS to alleviate bone destruction; (2) by reducing the secretion of cytokines by BMSCs, which are closely related to OS cell growth, migration, invasion, and tumorigenic osteogenesis.

Connection between Cardiac Fibrosis Biomarkers and Echocardiography Parameters in Advanced Chronic Kidney Disease Patients.

Myocardial fibrosis represents a mainstay pathway in the pathophysiology of uremic cardiomyopathy. This process leads to structural and functional changes in the heart, which can be detected by echocardiography. The purpose of our study was to determine the association between four echocardiographic parameters (ejection fraction (EF), global longitudinal strain (GLS), mean E/e' ratio, and left atrial volume indexed) and biomarkers associated with cardiac fibrosis, such as procollagen type I carboxy-terminal propeptide (PICP), procollagen type III N-terminal peptide (P3NP), and galectin-3 (Gal-3) in patients with end-stage renal disease (ESRD). 140 patients with ESRD were enrolled and investigated by echocardiography and the serum levels of the aforementioned biomarkers were determined at baseline. The mean EF was 53.63 ± 8%, the mean GLS was -10.2 ± 5.3%, the mean E/e' ratio was 9.8 ± 4.3, and the mean left atrial volume indexed (LAVI) was 45.8 ± 14.2 mL/m2. The average levels for PICP, P3NP, and Gal-3 were 457.2 ± 240 µg/L, 242 ± 199.9 µg/L, and 10.7 ± 3.7 ng/mL, respectively. In regression analysis, PICP was strongly associated with all four echocardiographic parameters (EF: p = 0.0002, R2 = 0.69; GLS: p = 0.00001, R2 = 0.81; mean E/e': p = 0.00002; R2 = 0.89; LAVI: p = 0.003; R2 = 0.73). P3NP and Gal-3 were only associated with the EF (p = 0.01, R2 = 0.31 and p = 0.02; R2 = 0.35, respectively). Our study evidenced that PICP, a collagen-derived biomarker, is associated with important echocardiography parameters, suggesting that it can serve as an indicator of the presence of subclinical systolic and diastolic dysfunction in patients with advanced CKD.

Health-related quality of life of men with primary osteoporosis and its changes after bisphosphonates treatment

IntroductionOsteoporosis leads to more serious consequences in men than in women, but less is known about its impacts on health-related quality of life (HRQoL) of men, and whether the anti-osteoporosis treatment can improve HRQoL of men with osteopenia/osteoprosis.MethodsWe enrolled men with primary osteoporosis and age-matched healthy controls. We collected medical history, serum levels of carboxyl-terminal type I collagen telopeptide, procollagen type I propeptides, and bone mineral density of patients. All patients and controls completed the short-form 36 (SF-36) questionnaires. Changes in HRQoL of osteopenia/osteoporosis men were prospectively evaluated after alendronate or zoledronic acid treatment.ResultsA total of 100 men with primary osteoporosis or osteopenia and 100 healthy men were included. The patients were divided into three subgroups: osteopenia (n = 35), osteoporosis (n = 39) and severe osteoporosis (n = 26). Men with osteoporosis or severe osteoporosis had impaired HRQoL in domains of physical health compared to healthy controls. HRQoL scores in physical health related domains of patients with severe osteoporosis were significantly lower compared to healthy controls, and were the poorest among the three subgroups of patients. Fragility fracture history was correlated with lower SF-36 scores about physical health. In 34 men with newly diagnosed osteoporosis receiving bisphosphonates treatment, HRQoL scores were significantly improved in domains of physical health after treatments.ConclusionsThe HRQoL is significantly impaired in men with osteoporosis, and the more severe the osteoporosis, the poorer the HRQoL. Fragility fracture is an important influencing factor of deteriorated HRQoL. Bisphosphonates treatment is beneficial to improve HRQoL of osteopenia/osteoporosis men.

Clinical observation of concentrated growth factor (CGF) combined with iliac cancellous bone and composite bone material graft on postoperative osteogenesis and inflammation in the repair of extensive mandibular defects

PurposeTo evaluate the effects of concentrated growth factor (CGF), combined with a mixture of iliac cancellous and composite bone materials, on the repair of extensive mandibular defects. Patients and MethodsThis clinical trial involved patients with mandibular defects caused by large cystic lesions. The test group comprised 16 patients who underwent CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular defects, whereas the control group comprised eight patients who underwent vascularised free fibula grafts for mandibular segmental defects. Postoperative exudatum was collected from patients on the 1st, 2nd, 3rd, and 4th days postoperatively, and osteogenic factor, including alkaline phosphatase (ALP), osteocalcin (BGP), and procollagen type I N-terminal propeptide (PINP), and inflammatory cytokines were performed. Additionally, regular cone beam computed tomography (CBCT) scans were conducted before and after surgery. ResultsOn postoperative days 1–4, the expression levels of ALP, BGP, and PINP were higher in the test group, while those of IL-1α, IL-1β, IL-6, IL-8, and TNF-α, which were identified as co-differentially expressing inflammatory cytokines, were all down-regulated in the exudatum of the test group. Regular CBCT radiological scans revealed a significant osteogenic effect in the test group. ConclusionThe use of CGF combined with iliac cancellous bone and composite bone materials to repair extensive mandibular jaw defects facilitates bone formation and reductions in inflammation in the defect area in the short term, which deserves further research in clinical practice.

Bone turnover markers reference database at University Medical Center, Ho Chi Minh city

Objectives: To establish reference ranges for serum bone turnover markers including Osteocalcin (OC), Procollagen type 1 amino-terminal propeptide (P1NP), and Beta-CrossLaps (beta-CTX) in premenopausal women at University Medical Center, Ho Chi Minh City. Methods: A cross-sectional study was conducted on 157 women aged 20 to 44 years at University Medical Center, Ho Chi Minh City from December 2022 to February 2023. Demographic information, biochemical markers, and serum levels of OC, P1NP, and beta-CTX were recorded. Results: The mean serum levels of OC, P1NP, and beta-CTX were 15.57 ± 4.75 ng/mL, 41.98 ± 16.62 μg/L, and 314.03 ± 150.42 pg/mL, respectively. The levels of bone turnover markers varied significantly among different age groups (p &lt; 0.01). Serum levels of OC, P1NP, and beta-CTX were negatively correlated with age, with r values of -0.44, -0.35 and -0.43 respectively (p &lt; 0.01). Conclusion: The reference ranges for serum markers of bone turnover including OC, P1NP, and beta-CTX were 15.57 ± 4.75 ng/mL, 41.98 ± 16.62 μg/L, and 314.03 ± 150.42 pg/mL, respectively, in premenopausal women aged 20 to 44 years. Serum levels of OC, P1NP, and beta-CTX were negatively correlated with age in a moderate degree Key words: osteocalcin, P1NP, beta-CTX, bone turnover markers, premenopausal women.

Delayed inhibition of collagen deposition by targeting bone morphogenetic protein 1 promotes recovery after spinal cord injury.

Fibrotic scars appear after spinal cord injury (SCI) and are mainly composed of fibroblasts and excess extracellular matrix (ECM), including different types of collagen. The temporal and spatial distribution and role of excess collagens and ECM after SCI are not yet fully understood. Here, we identified that the procollagen type I C-terminal propeptide (PICP), a marker of collagen type I deposition, and bone morphogenetic protein 1 (BMP1), a secreted procollagen c-proteinase (PCP) for type I collagen maturation, were significantly elevatedin cerebrospinal fluid of patients with SCI compared with healthy controls, and were associated with spinal cord compression and neurological symptoms. We revealed the deposition of type I collagen in the area damaged by SCI in mice and confirmed that BMP1 was the only expressed PCP and induced collagen deposition. Furthermore, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) can activate the expression of BMP1. However, inhibition of BMP1 at the acute phase eliminated fibrotic scars in the damaged area and inhibited activation and enrichment of astrocytes, which made the damage difficult to repair and increased hematoma. Unexpectedly, knockdown of Bmp1 by adeno-associated virus or the inhibition of BMP1 biological function by specific inhibitors and monoclonal antibodies at different time points after injury led to distinct therapeutic effects. Only delayed inhibition of BMP1 improved axonal regeneration and myelin repair at the subacute stage post-injury, and led to the recovery of motor function, suggesting that scarring had a dual effect. Early inhibition of the scarring was not conducive to limiting inflammation, while excessive scar formation inhibited the growth of axons. After SCI, the collagen deposition indicators increased in both human cerebrospinal fluid and mouse spinal cord. Therefore, suppression of BMP1 during the subacute phase improves nerve function after SCI and is a potential target for scar reduction.

Diagnostic value of ultrasound elastography combined with serological indicators in liver fibrosis in chronic hepatitis B

ABSTRACT To explore the value of ultrasound elastography combined with serological indicators in the diagnosis of liver fibrosis in chronic hepatitis B. A total of 156 patients with chronic hepatitis B from April 2020 to February 2022 were enrolled in this study as subjects. They were assigned to the liver fibrosis group (n=115) and the non-liver fibrosis group (n=41) according to whether the patients had liver fibrosis. They were divided into S1 stage (n=48), S2 stage (n=38), and S3 stage (n=29) according to histopathological staging criteria. Shear wave elastography (SWE) values, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen type III (PCIII), and laminin (LN) were compared among patients in each stage. Spearman’s method was utilized to analyze the correlation of liver serum biochemical indicators and SWE value with liver fibrosis. The predictive performance of SWE value and serological indicators was analyzed using receiver operating characteristic curves. According to Spearman’s method, the liver fibrosis stage was positively correlated with SWE value. Serological indicators combined with ultrasound elastography can accurately assess the degree of liver fibrosis in patients with chronic hepatitis B and provide a basis for clinical judgment.

Gly-Pro-Val-Gly-Pro-Ser Peptide Fish Collagen Improves Skin Moisture and Wrinkles with Ameliorated the Oxidative Stress and Pro-inflammatory Factors in Skin Photoaging Mimic Models.

This study aimed to investigate whether low molecular fish collagen peptide (FC) from Oreochromis niloticus had protective effects on skin of photoaging mimic models. We observed that FC supplementation improved antioxidant enzymes activities and regulated the pro-inflammatory cytokines [e.g., tumor necrosis factor-α, interleukin (IL)-1β, and IL-6] by reducing the protein expressions of pro-inflammatory factors IκBα, p65, and cyclooxygenase-2 in ultraviolet-B (UV-B) irradiated in vitro and in vivo. Furthermore, FC increased hyaluronic acid, sphingomyelin, and skin hydration by reg-ulating the mRNA expression of hyaluronic acid synthases 1∼3, serine palmitoyltransferase 1, delta 4-desaturase, sphingolipid 1, and protein expressions of ceramide synthase 4, matrix metalloproteinase (MMP)-1, -2, and -9. In UV-B irradiated in vitro and in vivo, FC down-regulated the protein expression of the c-Jun N-terminal kinase, c-Fos, c-Jun, and MMP pathways and up-reg-ulated that of the transforming growth factor-β receptor I, collagen type I, procollagen type I, and small mothers against decapentaplegic homolog pathways. Our results suggest that FC can be effective against UV-B induced skin photoaging by improving skin dryness and wrinkle formation through antioxidant and anti-inflammatory properties.

Bone Turnover Markers for Diagnosis of postmenopausal osteoporosis – A review

Postmenopausal osteoporosis is an age related skeletal metabolic disorder that affects most elderly women worldwide owing to the loss of estrogen activity, increase in bone turnover rate and circulating level of bone turnover markers. Although osteocalcin, bone specific alkaline phosphatase, and pro-collagen type I N- and C-terminal pro-peptides are considered as the most sensitive markers of bone formation however, they suffer some limitations. Consequently, periostin, sclerostin and dickkopf-1 protein (Dkk-1) are emerging diagnosis markers of bone pathologies and monitoring therapeutic interventions and management of postmenopausal osteoporosis. These markers serve as effective tools for diagnosis of bone disorders, predict reduction in fracture risk, reflect metabolic effect of drugs during bone remodeling and could be used to establish the lowest dose that elicit the required change in bone mineral density. Biological variability from different sources including controllable and uncontrollable factors could serve as the major limitations of these established markers of bone formation (BFMs). This review, therefore focus on the therapeutic applications of selected bone turnover markers for early diagnosis of postmenopausal osteoporosis.

Normocalcemic primary hyperparathyroidism is an early stage of primary hyperparathyroidism according to fibroblast growth factor 23 level.

Normocalcemic primary hyperparathyroidism is a variant of primary hyperparathyroidism with consistently normal albumin-adjusted or free-ionized calcium levels. It may be an early stage of classic primary hyperparathyroidism or could represent primary kidney or bone disorder characterized by permanent elevation of PTH level. The study aims to compare the FGF-23 levels in patients with PHPT, NPHPT, and normal calcium and PTH levels. Our study included patients who were referred to the endocrinology clinic with a presumptive diagnosis of primary hyperparathyroidism, an isolated increased level of PTH, or reduced bone densitometry. For each patient, we performed blood analysis of FGF-23, calcium, phosphate, vitamin D [25(OH)D3], estimated glomerular filtration rate (eGFR), bone turnover markers, and urine analysis for calcium/creatinine ratio. Our study included 105 patients. Thirty patients with hypercalcemic hyperparathyroidism (HPHPT group), thirty patients with elevated PTH and normal calcium levels (NPHPT group), and 45 patients with normal calcium and PTH levels in the control group. FGF 23 level was 59.5± 23 pg/ml in the NPHPT group, 77 ± 33 pg/ml in the HPHPT group, and 49.7 ± 21.7 pg/ml in the control group (p=0.012). The phosphate level was lowest in the HPHPT group: 2.9 ± 0.6 vs 3.5 ± 0.44 in the NPHPT and 3.8 ± 0.5 in the control groups (p=0.001). No differences were found in eGFR, 25(OH)D3, C-terminal telopeptide type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels, and bone densitometry scores between the three study groups. Our findings suggest that NPHPT is an early stage of PHPT. Further studies are needed to determine the role of FGF-23 and its usefulness in NPHPT.