- Evaluation of serum alkaline phosphatase measurement through the 4-year trueness verification program in China. [Journal Article]
- CCClin Chem Lab Med 2018 Sep 18
- Background Alkaline phosphatase (ALP) is critical for various diseases. The International Federation of Clinical Chemistry and Laboratory Medicine had recommended the new reference procedure in 2011,...
Background Alkaline phosphatase (ALP) is critical for various diseases. The International Federation of Clinical Chemistry and Laboratory Medicine had recommended the new reference procedure in 2011, but many manufacturers did not trace results to the higher procedure. Since 2012, the National Center for Clinical Laboratories (NCCL) in China has organized the trueness verification program (TV) with commutable materials. The present study summarizes the 4-year TV program to give an overview of the measurement standardization for ALP results. Methods Commutable serum-based materials with different concentrations were prepared and sent to participating laboratories. The target values were assigned by the reference lab network. Results The analytical performance was evaluated according to three indexes: trueness (bias), imprecision (CV) and accuracy (total error [TE]). The number of participating laboratories increased from 115 in 2012 to 287 in 2016. The pass rates of precision for homogeneous and heterogeneous systems were all above 85% over the 4 years; however, the pass rates of bias were much lower (<50%). Among the homogeneous systems, Roche Cobas/Modular had an obvious negative bias, whereas the mean positive bias for Beckman AU was prominent. As to the heterogeneous systems, the pass rates of bias for Sichuan Maccura (57.1%-78.6%) were higher than Roche Cobas/Modular (4.4%-33.9%) and Beckman AU (35.7%-64.8%). Conclusions The PT/EQA program with commutable materials can be used to assess the trueness against target values assigned by reference procedures. For ALP, homogeneous systems did not perform better than heterogeneous systems. The bias for ALP performance was notable and was the main obstacle to its standardization in China.
- Leonurine hydrochloride promotes osteogenic differentiation and increases osteoblastic bone formation in ovariectomized mice by Wnt/β-catenin pathway. [Journal Article]
- BBBiochem Biophys Res Commun 2018 Sep 14
- Leonurine hydrochloride (LH) is a synthetic chemical compound derived from leonurine that can be extracted from Leonurus sibiricus and possesses antioxidant, anti-apoptosis, and neuroprotective activ...
Leonurine hydrochloride (LH) is a synthetic chemical compound derived from leonurine that can be extracted from Leonurus sibiricus and possesses antioxidant, anti-apoptosis, and neuroprotective activities. In previous studies, LH has been demonstrated to attenuate osteoclast activity and prevent bone loss. However, it is unknown whether LH accelerates bone formation and promotes osteogenic differentiation. We systematically examined the effects of LH on ovariectomized-induced osteoporotic mice and the MC3T3-E1 osteoblastic cell line. The results revealed that LH enhanced differentiation of MC3T3-E1 cells, with a dose-dependent increase in alkaline phosphatase (ALP) activity. Moreover, LH upregulated osteogenesis-related gene expression, including osterix, alpha 1 type 1 collagen, runt-related transcription factor 2 (Runx2) and ALP, as shown by quantitative reverse transcription-polymerase chain reaction analysis. At the same time, elevated expression of low-density lipoprotein receptor-related protein 5 and β-catenin mRNA was detected in the Wnt/β-catenin pathway. A western blot analysis revealed that LH dose-dependently increased the expression of Runx2 and β-catenin, and promoted phosphorylation of glycogen synthase kinase-3β in vitro. The in vivo results showed that administering LH (15 mg/kg/d) for 8 weeks alleviated destruction of the trabecular microstructure caused by osteoporosis. LH increased the bone mineral density and trabecular number, decreased trabecular separation according to a micro-computed tomography scan. In addition, LH enhanced the expression of β-catenin and Runx2 in vivo. In conclusion, LH promoted osteogenic differentiation and bone formation in vivo and in vitro, which alleviated osteoporosis through activation of the Wnt/β-catenin pathway.
- Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis. [Journal Article]
- BPBiomed Pharmacother 2018 Sep 14; 108:280-287
- Diabetic osteoporosis is a complication of diabetes mellitus, and can result in an increased incidence of bone fractures and a delay in fracture healing. Berberine is one of the most widely distribut...
Diabetic osteoporosis is a complication of diabetes mellitus, and can result in an increased incidence of bone fractures and a delay in fracture healing. Berberine is one of the most widely distributed isoquinoline alkaloid in plants and possesses antioxidant properties. These properties can reduce the high glucose mediated in the dysfunction of human bone marrow stem cells. Therefore, the present study was designed to investigate the apparent beneficial effect of berberine on bone characteristics in streptozotocin plus HFD-induced diabetic rats. Rats were selected at random and divided into four groups: (A) control group (CG) (n = 10); (B) diabetic group (DG) (n = 10); (C) diabetic group with 50 mg kg-1day-1 of berberine (Brb-50) (n = 10); and (D) diabetic group with 100 mg kg-1day-1 of berberine (Brb-100) (n = 10). After 12 weeks of being treated with berberine, the femora from all rats were assessed and other blood biochemistries evaluated. Berberine at 50 mg/kg showed little effect and significance on diabetic osteopenia, while berberine at 100 mg/kg was significantly increased in diabetic rats. The same group also displayed a significantly decreased serum osteocalcin and serum alkaline phosphatase activity in diabetic rats. The impaired micro-architecture of the femurs in diabetic rats could partially be prevented by berberine with 100 mg/kg. In addition, berberine could to an extent restore the decreased bone formation and reabsorption of the femurs in diabetic rats through the histomorphometric analysis. Berberine could not only significantly lower the oxidative level of DNA damage, but also up-regulate the activity of serum antioxidants. According to our investigations and discoveries, we have found, that berberine may be a potential drug for controlling bone loss in diabetic osteoporosis.
- Epigallocatechin‑3‑gallate protects against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. [Journal Article]
- MMMol Med Rep 2018 Sep 03
- Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, ...
Epigallocatechin‑3‑gallate (EGCG) is a polyphenolic compound extracted and isolated from green tea, which has a variety of important biological activities in vitro and in vivo, including anti‑tumor, anti‑oxidation, anti‑inflammation and lowering blood pressure. The aim of the present study was to investigate the protective effect of EGCG against secondary osteoporosis in a mouse model via the Wnt/β‑catenin signaling pathway. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were used to analyze runt‑related transcription factor 2 and osterix mRNA expression, and the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression. The protective effect of EGCG against secondary osteoporosis was examined and its potential mechanism was analyzed. Treatment with EGCG significantly decreased serum calcium, urinary calcium, body weight and body fat, and increased leptin levels in mice with secondary osteoporosis. In addition, EGCG treatment significantly inhibited the structure score of articular cartilage and cancellous bone in proximal tibia metaphysis in mice with secondary osteoporosis. Treatment also significantly decreased alkaline phosphatase activity, runt‑related transcription factor 2 and osterix mRNA expression. EGCG also significantly induced the protein expression of cyclin D1, Wnt and β‑catenin, and suppressed peroxisome proliferator‑activated receptor γ protein expression in mice with secondary osteoporosis. Taken together, these results suggest that EGCG may be a possible new drug in clinical settings.
- Protective effects of α‑2‑macroglobulin on human bone marrow mesenchymal stem cells in radiation injury. [Journal Article]
- MMMol Med Rep 2018 Sep 04
- Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of pat...
Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of patients. Human bone marrow mesenchymal stem cells (hBMMSCs) are a cell type with self‑renewal and pluripotent differentiation potential in the bone marrow stroma. These cells are associated with bone tissue regeneration and are one of the primary cell types affected by bone tissue radiation injury. α‑2‑macroglobulin (α2M) is a glycoprotein‑rich macromolecule that interacts with cytokines, growth factors and hormones to serve a variety of biological roles. In addition, α2M possesses radio‑protective effects. The aim of the present study was to investigate whether α2M has protective effects against radiation injury of hBMMSCs. Cell counting kit‑8 and colony formation assays were used to monitor cell proliferation. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction were used to detect Beclin1, microtubule‑associated protein 1A/1B, sex determining region Y, Nanog, runt‑related transcription factor 2, osteoglycin and manganese superoxide dismutase expression. The formation of calcium nodules was evaluated by Alizarin red staining after osteogenic induction. Flow cytometric analysis of Annexin‑V and propidium iodide double staining was used to detect changes in apoptosis rate. Alkaline phosphatase and superoxide dismutase activity were determined using colorimetric assays. Reactive oxygen species levels were detected using 2',7'‑dichlorodihydrofluorescein diacetate. The results of the present study revealed that α2M increased the rate of proliferation, reduced autophagy, alleviated pluripotent differentiation injury, increased the osteogenic differentiation ability and decreased the rate of apoptosis in hBMMSCs following irradiation via an antioxidative pathway. In conclusion, α2M exhibited protective effects against radiation injury in hBMMSCs and may be considered a potential therapeutic agent for the prevention and treatment of ORNJ.
- Anti-obesity and fatty liver-preventing activities of Lonicera caerulea in high-fat diet-fed mice. [Journal Article]
- IJInt J Mol Med 2018 Sep 14
- Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed ...
Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP‑activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non‑alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti‑obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high‑fat diet (HFD)‑fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ‑glutamyltransferase, total cholesterol, low‑density lipoprotein and TG, with the exception of high‑density lipoprotein) were observed in HFD‑fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPKα1 and AMPKα2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose‑6‑phosphatase activity, hepatic acetyl‑CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer‑binding protein (C/EBP) α, C/EBPβ and sterol‑regulatory‑element‑binding protein 1c mRNA in the periovarian tissue. Furthermore, non‑alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.
- The influence of thyroid disorders on bone density and biochemical markers of bone metabolism. [Journal Article]
- HMHorm Mol Biol Clin Investig 2018 Sep 15; 35(1)
- Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of ...
Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.
- Effect of sitagliptin, a DPP-4 inhibitor, against DENA-induced liver cancer in rats mediated via NF-κB activation and inflammatory cytokines. [Journal Article]
- JBJ Biochem Mol Toxicol 2018 Sep 15; :e22220
- The target of the current research was to investigate the anticancer activity of sitagliptin on diethylnitrosamine (DENA)-induced cancer in the liver. Wistar rats were treated with or without sitagli...
The target of the current research was to investigate the anticancer activity of sitagliptin on diethylnitrosamine (DENA)-induced cancer in the liver. Wistar rats were treated with or without sitagliptin before DENA treatment. We detected liver weight, blood glucose, and histopathology of the liver. Serum biochemical markers like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SALP), gamma-glutamyl transpeptidase (GGTP), total bilirubin (TBR), total protein (TPR), and albumin (ALB) were also evaluated. In addition, lipid profile parameters comprising total cholesterol (TC), triglycerides, and high-density lipoprotein were also measured. Inflammatory mediators like interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were determined in liver homogenate. Furthermore, the activity of nuclear factor (NF-κB) was also measured. Our results showed that sitagliptin (10 and 20 mg/kg) in a dose-dependent manner expressively decreased the DENA-induced elevation of SGPT, SGOT, SALP, and GGTP. Whereas sitagliptin (10 and 20 mg/kg) in a dose-dependent mode reduced the level of TBR and increased the TPR and ALB as well as improved the liver histopathology alterations in DENA-exposed rats. Lipid profile was also restored by the sitagliptin (10 and 20 mg/kg) in a DENA-treated rats. The level of IL-1β, IL-6, and TNF-α were suggestively suppressed. Moreover, pretreatment with sitagliptin (10 and 20 mg/kg) prevented the activation of NF-κB. In conclusion, sitagliptin (10 and 20 mg/kg) has a potential protective effect against DENA-induced liver cancer by inhibition of inflammation and NF-κB activation.
- Aloin promotes osteogenesis of bone-marrow-derived mesenchymal stem cells via the ERK1/2-dependent Runx2 signaling pathway. [Journal Article]
- JNJ Nat Med 2018 Sep 14
- Osteoporosis is characterized by low bone mass and the degeneration of bone structure, conditions which increase the risk of fracture. Aloin has been shown to affect bone metabolism, but its role in ...
Osteoporosis is characterized by low bone mass and the degeneration of bone structure, conditions which increase the risk of fracture. Aloin has been shown to affect bone metabolism, but its role in osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. The aim of our study was to determine whether aloin promotes the proliferation and osteogenic differentiation of BMSCs and, if so, whether it acts via activation of the ERK1/2-Runx2 signaling pathway. We found that the different concentrations of aloin tested had no obvious cytotoxic effects on the viability of BMSCs. Under osteogenic induction conditions, aloin increased cellular alkaline phosphatase activity, promoted BMSC mineralization, and increased osteogenic-related gene expression. In addition, treating the BMSCs with the signal transduction inhibitor PD98059 (ERK1/2) effectively attenuated Runx2 activation in these cells and also suppressed osteoblastic differentiation. Overall, our study demonstrates that aloin promotes osteogenic differentiation of BMSCs through activation of the ERK1/2-Runx2 signaling pathway.
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- Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women. [Journal Article]
- MRMod Rheumatol 2018 Sep 14; :1-15
- CONCLUSIONS: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.