Decreased Serum Level of Sclerostin in Older Adults with Sarcopenia.

BACKGRUOUND: Although muscles and bones interact with each other through various secretory factors, the role of sclerostin, an osteocyte-secreted factor, on muscle metabolism has not been well studied. We investigated the levels of serum sclerostin in Korean older adults with sarcopenia. METHODS: Blood samples were collected from 129 participants who underwent evaluation of muscle mass and function in an outpatient geriatric clinic of a teaching hospital. Sarcopenia and related parameters were determined using cutoff values for the Asian population. Serum sclerostin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the participants was 69.6 years, and 20 participants (15.5%) were classified as having sarcopenia. After adjusting for age, sex, and body mass index, serum sclerostin levels were significantly lower in participants with sarcopenia, low muscle mass, or weak muscle strength (P=0.003 to 0.045). Serum sclerostin levels were positively associated with skeletal muscle index and grip strength after adjusting for confounders (P=0.001 and P=0.003), whereas sarcopenic phenotype score showed a negative association (P=0.006). These increases in muscle mass and strength were also dose dependent as serum sclerostin levels increased (P for trends=0.003 and P for trends=0.015). Higher serum sclerostin levels were associated with lower odds ratio (ORs) for sarcopenia, low muscle mass, and weak muscle strength after adjusting for confounders (OR, 0.27 to 0.50; P<0.001 to 0.025). CONCLUSION: Higher serum sclerostin levels were associated with a lower risk of sarcopenia, low muscle mass, and weak muscle strength in Korean older adults.

Benefits of lumican on human bone health: clinical evidence using bone marrow aspirates.

BACKGROUND/AIMS: Lumican, a small leucine-rich proteoglycan, has shown osteoprotective effects by synchronously stimulating bone formation and suppressing bone resorption. To clarify the role of lumican in human bone metabolism, the association between lumican concentrations and osteoporosis-related phenotypes was evaluated using bone marrow (BM) samples directly reflecting local microenvironments. METHODS: BM aspirates were obtained from 77 patients during hip surgery for either fragility hip fractures (HF) (n = 29) or osteoarthritis (n = 48) and centrifuged. Concentrations of lumican and biochemical bone markers in BM supernatants were measured using enzyme linked immunosorbent assays. RESULTS: After considering confounders, lumican concentrations in BM supernatants were 16.9% lower in patients with HF than in controls, with each increase in the standard deviation of lumican concentration being associated with a 61% lower likelihood of HF. The odds ratios for HF decreased linearly with increasing lumican tertiles in BM, with the odds of having fragility HF markedly lower in participants in the highest than in the lowest lumican tertile. Higher lumican level correlated significantly with higher femur neck bone mineral density and higher bone-specific alkaline phosphatase levels, but not with tartrate-resistant acid phosphatase 5b concentrations, in BM supernatants. CONCLUSION: These data clinically validate previous in vitro and animal experiments showing the beneficial roles of lumican for bone homeostasis and suggest that lumican may contribute to a reduction in fracture risk in humans mainly through its stimulation of bone formation.

Serum irisin level is independent of sarcopenia and related muscle parameters in older adults.

BACKGROUND: Accumulating evidence indicates that irisin, a myokine consisting of 112 amino acids, protects against muscle wasting in an autocrine manner; however, its impact on human muscle metabolism is still inconclusive. In this cross-sectional study, we aimed to investigate whether circulating irisin could be a potential biomarker reflecting muscle health in older adults. METHODS: Comprehensive assessment of muscle mass; muscle function, including grip strength, gait speed, chair stand test, and short physical performance battery (SPPB); and muscle quality was performed in 143 older adults who visited outpatient geriatrics and endocrinology clinics. Sarcopenia was defined using the Asian-specific cutoff value. Blood samples were also collected to determine serum irisin concentration which was measured using enzyme immunoassay. RESULTS: The serum irisin level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, poor physical performance, and poor muscle quality, before or after adjustment for age, sex, appendicular skeletal muscle (ASM), and body mass index. Consistently, the association of circulating irisin level with sarcopenia-related parameters (skeletal muscle index, grip strength, gait speed, chair stand test, SPPB, and grip strength/body weight or ASM) was not evident in any adjustment models. CONCLUSIONS: Despite the clear implication of irisin's involvement in muscle metabolism based on experimental research, we did not observe a definite association between its serum level and clinical muscle parameters in humans. These results suggest that the blood irisin level may not accurately predict the risk of sarcopenia in older adults.

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor.

BACKGROUND: Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. METHODS: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reversetranscription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. RESULTS: Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. CONCLUSION: These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.

Hierarchical Stereo Matching in Two-Scale Space for Cyber-Physical System.

Dense disparity map estimation from a high-resolution stereo image is a very difficult problem in terms of both matching accuracy and computation efficiency. Thus, an exhaustive disparity search at full resolution is required. In general, examining more pixels in the stereo view results in more ambiguous correspondences. When a high-resolution image is down-sampled, the high-frequency components of the fine-scaled image are at risk of disappearing in the coarse-resolution image. Furthermore, if erroneous disparity estimates caused by missing high-frequency components are propagated across scale space, ultimately, false disparity estimates are obtained. To solve these problems, we introduce an efficient hierarchical stereo matching method in two-scale space. This method applies disparity estimation to the reduced-resolution image, and the disparity result is then up-sampled to the original resolution. The disparity estimation values of the high-frequency (or edge component) regions of the full-resolution image are combined with the up-sampled disparity results. In this study, we extracted the high-frequency areas from the scale-space representation by using difference of Gaussian (DoG) or found edge components, using a Canny operator. Then, edge-aware disparity propagation was used to refine the disparity map. The experimental results show that the proposed algorithm outperforms previous methods.

Simultaneous determination of plant growth regulator and pesticides in bean sprouts by liquid chromatography-tandem mass spectrometry.

A simple and sensitive analytical method based on QuEChERS approach using liquid chromatography tandem mass spectrometry was developed and validated for the determination of 6-benzylaminopurine, carbendazim and thiabendazole in bean sprouts. Sodium chloride and sodium acetate were used for salting-out step and magnesium sulfate for clean-up. The validation of optimized method was satisfactory with recoveries, between 89.5% and 103.2% for the three compounds, and relative standard deviation (RSD) values less than 3.3% at 20 and 40ng/g fortification levels (n=5). Limit of detection (LOD) and limit of quantification (LOQ) was 2.1-3.7ng/g and 6.3-11.1ng/g, respectively. Monitoring of 126 bean sprout samples collected from local markets was performed to verify the adaptability in real samples. No pesticides were detected but 6-benzylaminopurine was found in 3 samples at the level of 15-20ng/g. The optimized method should be applicable for monitoring of 6-benzylaminopurine, carbendazim and thiabendazole in bean sprouts in short time.

The combination of TRAIL treatment and cancer cell selective expression of TRAIL-death receptor DR4 induces cell death in TRAIL-resistant cancer cells.

The human telomerase reverse transcriptase (hTERT) promoter can be used for the tumor-specific expression of transgenes in order to induce selective cancer cell death. The hTERT core promoter is active in cancer cells but not in normal cells. To examine whether the combination of TNF-related apoptosis inducing ligand (TRAIL) treatment and cancer cell-selective expression of the TRAIL-death receptor could induce cell death in TRAIL-resistant cancer cells, we generated a death receptor-4 (DR4)-expressing adenovirus (Ad-hTERT-DR4), in which the expression of DR4 is driven by the hTERT promoter. Upon infection, DR4 expression was slightly increased in cancer cell lines, and cell death was observed in TRAIL-resistant cancer cell lines but not in normal human cells when DR4 infection was combined with TRAIL treatment. We also generated an adenovirus that expresses a secretable isoleucine zipper (ILZ)-fused, extracellular portion of TRAIL (Ad-ILZ- TRAIL). In cells infected with Ad-ILZ-TRAIL, TRAIL was expressed, secreted, oligomerized and biologically active in the induction of apoptosis in TRAIL-sensitive cancer cells. When Ad-hTERT-DR4 infected TRAIL-resistant HCE4 cells and Ad-ILZ-TRAIL infected TRAIL-resistant HCE7 cells were co-cultured, cell deaths were evident 24 h after co-culture. Taken together, our results reveal that the combination of TRAIL and cancer cell-specific expression of DR4 has the potential to overcome the resistance of cancer cells to TRAIL without inducing significant cell death in normal cells.

Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer.

OBJECTIVE: The aim of this study was to determine midkine (MK) and pleiotrophin (PTN) expression in cervical cancer. METHODS: Prospective study in tertiary teaching hospital. Normal and cancerous cervical tissues were obtained from healthy women (n = 19) and from patients with cervical cancer (n = 42). The expressions of MK and PTN mRNA and protein were examined by quantitative competitive PCR and by immunohistochemistry. MK and PTN mRNA and protein expressions were examined with respect to tumor stage and size. RESULTS: The expressions of midkine and pleiotrophin mRNA in cervical cancer were higher than those in the normal cervix (MK, 175.59 +/- 63.3 vs 1.00 +/- 0.18 fmol, respectively; PTN, 3.18 +/- 1.25 vs. 0.86 +/- 0.12 fmol, respectively, P < 0.05), and their expressions were not correlated with cervical cancer stage or size of the tumor. The expressions of MK and PTN protein in cancerous tissue were higher than those in the normal cervix (P < 0.05). Moreover, the protein expression of MK, but not of PTN, correlated with tumor stage and size. The expressions of MK and PTN were not correlated with vascular density. CONCLUSIONS: Our results suggest that increased midkine mRNA and protein expressions are associated with the carcinogenesis of cervical cancer.