The aim of the case study is to examine the association between hypertension and the level of bone metabolism markers in newly diagnosed osteoporotic patients. A cross-sectional study of 518 subjects was done to see the association between hypertension and the level of osteocalcin (OC), bone-specific alkaline phosphatase (B-ALP), Tartrate-resistant acid phosphatase (TRAP.5B), and 25-hydroxy vitamin D (25-OHD). There were 243 (46.9%) osteoporosis patients with hypertension. Both univariate and multivariate analysis have suggested that lower OC and 25-OHD levels were associated with hypertension. The potential confounders-adjusted OC level was significantly lower in hypertensive female group than that in the female without hypertension group [β = -0.20, 95% confidence interval (95% CI) = -0.37 to -0.03, P = .02 in final adjust model]. The potential confounders-adjusted 25-OHD level was significantly lower in hypertensive male group than that in male without hypertension group (β = -0.34, 95% CI = -0.58 to -0.10, P = .01 in final adjust model). The B-ALP and TRACP.5B levels were positively associated with hypertension in all patients or subgroup analysis. However, all the correlations had no statistical significance for the B-ALP and TRACP.5B. In conclusion, the hypertension was associated with low level of OC and 25-OHD. Hypertension probably led to low bone turnover, which may be one of the mechanisms of hypertension-related osteoporosis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the present study, we investigated the pharmacologic effect and molecular mechanism of Danshensu in AS. Potential targets of Danshensu were identified in four drugs-genes databases; and potential pharmacologic target genes in AS were identified in three diseases-genes databases. Differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database. Overlapping targets of Danshensu and AS were determined and a disease–active ingredient–target interaction network was constructed with Cytoscape software. Enrichment analyses of the common targets were performed using Bioconductor. To test the validity of the constructed network, an in vitro model was established by treating osteoblasts from newborn rats with low concentrations of tumor necrosis factor (TNF)-α. Then, the in vitro model and AS fibroblasts were treated with Danshensu (1–10 μM). Osteogenesis was evaluated by alkaline phosphatase staining and activity assay, alizarin red staining, quantitative PCR, and western blotting. We identified 2944 AS-related genes and 406 Danshensu targets, including 47 that were common to both datasets. The main signaling pathways associated with the targets were the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. A low concentration of TNF-α (0.01 ng/ml) promoted the differentiation of osteoblasts; this was inhibited by Danshensu, which had the same effect on AS fibroblasts but had the opposite effect on normal osteoblasts. Danshensu also decreased the phosphorylation of JNK and ERK in AS fibroblasts. There results provide evidence that Danshensu exerts an anti-osteogenic effect via suppression of JNK and ERK signaling, highlighting its therapeutic potential for the treatment of AS.

Background: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. Methods: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. Results: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. Conclusions: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. Trial registration: ClinicalTrials.gov Identifier: NCT03030508.

Background/Aims: In this study we assessed histomorphometric changes induced by thyroxine (T4) in 3-month-old hyperthyroid male rats and examined whether the potential mechanism of these changes is related to bone changes. Methods: Rats were classified as either hyperthyroid following administration of 250 µg/kg/day freshly prepared T4 by gavage for 2 months or euthyroid following administration of vehicle alone (n = 8 per group). We measured bone mineral density (BMD), bone biomechanical properties, and bone histomorphometric changes. Levels of serum indicators were also measured, and three right femurs from the two groups were selected for proteomic investigation. Results: Compared with the control rats, hyperthyroid rats showed a reduction in the fifth lumbar vertebral BMD as well as in the entire femoral BMD (p = 0.033 and 0.026, respectively). Histomorphometric analysis of the proximal tibial metaphysis showed that the percentage of the trabecular area, trabecular number, and percentage of the cortical bone area in the hyperthyroid rats significantly decreased compared with those of the control rats. Conversely, bone formation rate (per unit of bone surface and bone volume), percentage of the osteoclast perimeter, trabecular separation, and endosteal mineral apposition rate in the hyperthyroid rats significantly increased compared with the control rats (all p < 0.05). Except for stiffness (p = 0.24), all bone biomechanical properties of the femur showed a significant decreasing trend in the hyperthyroid rats versus the control rats (all p < 0.05). Serum levels of osteocalcin, alkaline phosphatase, terminal telopeptides of type β collagen, and tartrate-resistant acid phosphatase were higher in the hyperthyroid rats than in the control rats (all p < 0.05). Using isobaric tags for relative and absolute quantification (iTRAQ), the expression levels of 1,310 proteins were found to be significantly different between the hyperthyroid and control rats (711 proteins were upregulated and 599 were downregulated in hyperthyroid rats). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that most of the enzymes in the glycolysis–tricarboxylic acid (TCA) cycle–oxidative phosphorylation signalling pathway were upregulated in hyperthyroid rats, and seven differentially expressed proteins were selected to verify the iTRAQ results using western blotting. Conclusion: Energy metabolism via the glycolysis–TCA cycle–oxidative phosphorylation pathway is positively associated with T4-induced bone histomorphometric changes in rats.

Objective: To investigate the role of growth differentiation factor 15 (GDF‐15) in ankylosing spondylitis (AS). Methods: A proteoglycan‐induced arthritis mouse model was established to mimic the pathologic changes of AS. Expression of GDF‐15 in serum and the edge of the vertebral cartilage plate and the spinal entheseal sites in the model group was detected by enzyme‐linked immunosorbent assay and immunohistochemistry. Then primary fibroblasts from the ligaments of patients with femoral neck fracture (healthy controls [HC]) and patients with AS were extracted. Western blotting, alkaline phosphatase (ALP) staining and activity assay, and alizarin red staining were used to detect the osteogenic ability of primary fibroblasts. Results: Expression of GDF‐15 was up‐regulated in serum and the edge of the vertebral cartilage plate and the spinal entheseal sites in the model group. In vitro, our results showed that GDF‐15 promoted the osteogenic differentiation of HC and AS fibroblasts. Furthermore, our results showed that in AS fibroblasts, GDF‐15 elevated the expression of osteogenic marker genes ( SP7 , RUNX2 , and COL1 ) as well as p‐glycogen synthase kinase 3β and β‐catenin, which are involved in the Wnt/β‐catenin signaling pathway. This effect of GDF‐15 in AS fibroblasts could be reversed by the inhibitor of the Wnt/β‐catenin signaling pathway, DKK‐1, suggesting that GDF‐15 promoted the osteogenic differentiation of AS fibroblasts via the Wnt/β‐catenin signaling pathway. Furthermore, knockdown of GDF‐15 also suppressed osteogenic differentiation and inhibited Wnt/β‐catenin signaling in AS fibroblasts. Conclusion: This study revealed aberrant up‐regulation of GDF‐15 in an AS mouse model and osteogenic effect of GDF‐15 in AS fibroblasts via the Wnt/β‐catenin signaling pathway, which may be one of the mechanisms and therapeutic targets of new bone formation in AS.

Calcium homeostasis imbalance is one of the important pathological mechanisms in heart failure. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), a calcium ATPase on the sarcoplasmic reticulum in cardiac myocytes, is a myocardial systolic-diastolic Ca2 + homeostasis regulating enzyme that is not only involved in cardiac diastole but also indirectly affects cardiac myocyte contraction. SERCA2a expression was found to be decreased in myocardial tissue in heart failure, however, there are few reports on serum SERCA2a expression in patients with heart failure, and this study was designed to investigate whether serum SERCA2a levels are associated with the occurrence of adverse events after discharge in patients hospitalized with heart failure. Patients with heart failure hospitalized in the cardiovascular department of the Second Affiliated Hospital of Guangdong Medical University, China, from July 2018 to July 2019 were included in this study, and serum SERCA2a concentrations were measured; each enrolled patient was followed up by telephone after 6 months (6 ± 1 months) for general post-discharge patient status. The correlation between serum SERCA2a levels and the occurrence of adverse events (death or readmission due to heart failure) after hospital discharge was assessed using multiple analysis and trend analysis. Seventy-one patients with heart failure were finally included in this study, of whom 38 (53.5%) were men and 33 (46.5%) were women (All were postmenopausal women). Multiple analysis revealed no correlation between serum SERCA2a levels and the occurrence of adverse events in the total study population and in male patients, but serum SERCA2a levels were associated with the occurrence of adverse outcome events after hospital discharge in female patients (OR = 1.02, P = .047). Further analysis using a trend analysis yielded a 4.0% increase in the risk of adverse outcomes after hospital discharge for each unit increase in SERCA2a in female patients (OR = 1.04; P = .02), while no significant difference was seen in men. This study suggests that serum SERCA2a levels at admission are associated with the occurrence of post-discharge adverse events in postmenopausal female patients hospitalized with heart failure.