Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Associations of Serum Selenium Levels in the First Trimester of Pregnancy with the Risk of Gestational Diabetes Mellitus and Preterm Birth: a Preliminary Cohort Study.

Women with gestational diabetes mellitus (GDM) may have lower serum selenium levels than healthy controls, which may be associated with preterm birth. We explored the association of serum selenium levels in early pregnancy with the risk of GDM and preterm birth among Chinese women. We included 398 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Serum selenium levels were measured in the first trimester. After delivery, data concerning mothers and their children were sourced from medical records by researchers who were blind to the participants' selenium status. Of the 398 women, 71 (17.8%) had GDM, 21(5.3%) had preterm birth, and 266 (66.8%) had selenium deficiency (serum selenium < 70 µg/L). Women in the upper three quartiles of serum selenium level did not have a significantly lower risk of GDM or preterm birth than those in the lowest quartile after adjustment for covariates (all p > 0.05). When serum selenium levels were classified as normal or deficient, the risk of GDM or preterm birth among women with normal serum selenium levels was still not lower than that of women with deficient serum selenium levels after adjustment for covariates (all p > 0.05). Although selenium deficiency was common in the Chinese women in our cohort, our results indicate that low serum selenium level during early pregnancy may not be a strong predictor of the risk of GDM and preterm birth. However, our sample size was small, and future studies with larger populations are warranted.

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention.

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Up-regulation of RNF187 induces hepatocellular carcinoma cell epithelial to mesenchymal transitions.

Ring finger protein 187 (RNF187) has been identified to be a co-activator linking c Jun to Ras signaling. However, the expression and function of RNF187 in hepatocellular carcinomas (HCC) remains unclear. Here, we tried to determine the expression and roles of RNF187 in hepatocellular carcinomas (HCC).The expression of RNF187 was determined in HCC tissues and cell lines, and we found that RNF187 expressed highly in HCC tissues compared with the corresponding adjacent liver tissues both in mRNA and protein level, which was consistent with the result of immunohistochemistry on HCC tissue microarrays. In HCC cell lines, the level of RNF187 was positively associated with the HCC cells metastatic potential. By the RNF187 interference and cDNA transfection, we showed that the high level of RNF187 induced the HCC cells invasion and metastasis both in vitro and in vivo, as well as the high ability of colony formation.Mechanistically, we detected the high level of RNF187 promoted cell scatter by inducing epithelial-mesenchymal transition (EMT). Clinically, the high level of RNA187 was significantly correlated with a malignant phenotype, including larger tumor size, multiple tumors, and microvascular invasion. Importantly, high level of RNF187 correlated with HCC patients' shorter OS and lower disease free survival rates than those with low level of RNF187. Our results revealed that elevated expression of RNF187 induced hepatocellular carcinoma cell epithelial to mesenchymal transitions, and represented a novel marker for predicting the poor prognosis of HCC.

[Correlation between neonatal vitamin D level and maternal vitamin D level].

OBJECTIVE: To investigate the correlation between neonatal and maternal vitamin D levels. METHODS: From June 1 to July 10, 2015, umbilical venous blood samples were collected from 102 full-term single neonates, and venous blood samples were collected from their mothers. Ultra-performance liquid chromatography with isotope dilution was applied to measure the serum 25(OH)D level. RESULTS: Vitamin D insufficiency was found in 39 mothers (38.2%) and 27 neonates (26.5%), and vitamin D deficiency was found in 25 mothers (24.5%) and 66 neonates (64.7%). Neonatal serum 25(OH)D level differed significantly between the groups of mothers with different serum 25(OH)D levels (P<0.001). Maternal 25(OH)D level was positively correlated with neonatal vitamin D level (r=0.914, P<0.001). When the receiver operating characteristic curve for maternal 25(OH)D level was used to predict neonatal vitamin D deficiency (≤15 ng/mL), the area under the curve was 0.962 (95%CI: 0.930-0.994; P<0.001). The sensitivity and specificity of maternal serum 25(OH)D level≤27.55 ng/mL to predict neonatal vitamin D deficiency were 97.2% and 80.3%, respectively. CONCLUSIONS: Neonatal vitamin D level is positively correlated with maternal vitamin D level. Maternal vitamin D level can help to predict neonatal vitamin D deficiency.

Variability of Metal Levels in Spot, First Morning, and 24-Hour Urine Samples over a 3-Month Period in Healthy Adult Chinese Men.

BACKGROUND: Metals in single spot urine samples are often used to estimate individual exposure in human studies. However, measurements in urine could vary greatly over time due to variable exposure, potentially leading to exposure misclassification. OBJECTIVE: We examined the variability of metal levels in the urine of 11 men who provided 529 samples on 8 days during a 3-month period, which corresponds to the duration of spermatogenesis. METHOD: The urinary levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), molybdenum (Mo), and nickel (Ni) were measured using inductively coupled plasma-mass spectrometry. We calculated the intraclass correlation coefficients (ICCs) to assess the reproducibility of metal measures and computed the sensitivity and specificity to evaluate how well spot urine samples determined the individuals' 3-month average exposure. RESULTS: Fair to good reproducibility was observed for the serial measurements of Cd (ICC = 0.53) in spot samples collected during the 3-month period, whereas the serial measurements of As, Co, Cu, Pb, Mo, and Ni showed poor reproducibility (ICCs = 0.01-0.29). Use of single spot urine samples to classify the high (top 33%) 3-month average metal levels had uniformly high specificities (0.70-0.84) but relatively low sensitivities (0.40-0.57), except for Cd (0.77). The minimum number of specimens (k) required to estimate the participant-specific mean for the seven metals within 20% of the "true" values ranged from 3 for Cd to 27 for Ni. CONCLUSIONS: The high variability observed in the urinary levels of As, Co, Cu, Pb, Mo, and Ni suggests that a single measurement provides only a brief snapshot in time of the exposure levels of an individual, which can result in a moderate degree of exposure misclassification. CITATION: Wang YX, Feng W, Zeng Q, Sun Y, Wang P, You L, Yang P, Huang Z, Yu SL, Lu WQ. 2016. Variability of metal levels in spot, first morning, and 24-hour urine samples over a 3-month period in healthy adult Chinese men. Environ Health Perspect 124:468-476; http://dx.doi.org/10.1289/ehp.1409551.

[Effects of drip irrigation methods on the regulation between root and crown function of 'Cabernet Sauvignon' seedlings].

The objective of this experiment was to study the effects of three irrigation methods, i.e., subsurface drip irrigation with a tank system (SDI) , plastic film mulched-drip irrigation (MDI), and conventional drip irrigation (DI) on the regulation between root and crown function of Vitis vinifera 'Cabernet Sauvignon' seedlings. The results showed that both the SDI and MDI systems promoted the growth of the grape seedlings compared with DI, with the SDI system promoting the root growth, and MDI system promoting the aboveground growth. Root area, root volume, and root activity and SOD enzyme activity in the SDI treatment were greater than those of MDI or DI treatment in the 20-60 cm soil layer. SDI treatment increased root penetration and physiological activity. Symptoms of drought stress appeared earlier in DI treatment than in either MDI or SDI treatment in the same watering schedule. Net photosynthetic rate (Pn) and stomatal conductance (g(s)) of leaves were higher in SDI and MDI treatments than in DI treatment. ΦPS II and qP at 12:00-14:00 were lower in the MDI treatment than in SDI treatment at 7 d after irrigation, suggesting that the degree of photoinhibition in the fluorescence process in MDI treatment was more than that in SDI treatment. The high biomass and physiological activity of roots in the 20-40 cm depth could increase both of total plant biomass and aboveground biomass. The regulation between root and crown function was better in SDI treatment than in MDI and DI treatments. Therefore, SDI could be used as an alternative technique of water-saving irrigation practices.

Values of iodine metabolism biomarkers in assessing the iodine nutrition status in surgically treated patients with thyroid disease.

OBJECTIVE: To assess the clinical application value of iodine metabolism biomarkers in assessing iodine nutrition status in surgically treated patients with thyroid disease. METHODS: Blood,morning urine and 24-hour urine samples were collected in 31 healthy volunteers and in 30 surgically treated patients with thyroid disease before and after surgery. Iodine concentration was analyzed by inductively coupled plasma mass spectrometry. The iodine metabolism biomarkers including serum iodine (SI), morning urine iodine(UI), morning urine iodine/urine creatinine ratio (UI/UCr), 24-hour urine iodine (24 h UI), and 24-hour urine iodine excretion (24 h UIE) were evaluated in these two groups. In addition, the validation coincidence rate of iodine metabolism biomarkers in healthy volunteers to different reference ranges including World Health Organization, Mayo Clinic, and Quest Diagnostics were calculated. RESULTS: The UI/UCr ratio of pre-operative thyroid disease patients was significantly lower than that of healthy volunteers (P<0.05), while the other biomarkers showed no significant differences (all P>0.05) between these two groups. The SI, UI ,and 24 h UI in postoperative thyroid disease patients were significantly higher than those of the pre-operative patients (all P<0.05). Though the medians of all biomarkers in healthy volunteers were within the reference ranges,only the validation coincidence rates of SI, UI, and UI/UCr in the 41-70-year populations were over than 90% according to Mayo Clinic; furthermore, the area under the receiver operating characteristic curve about UI/UCr ratio (0.737) was the biggest within the iodine metabolism biomarkers. CONCLUSION: The UI/UCr ratio may be used for iodine nutrition evaluation in surgically treated patients with thyroid disease.

[Study on detection methods of interstitial fluid glucose concentration based on infrared attenuated total reflection].

Measuring the glucose concentrations in the interstitial fluid is currently the main method to achieve the continuous blood glucose monitoring. The MIR-ATR(Mid-infrared, Attenuated Total Reflection)Spectroscopy has prominent advantage on the analysis of small biological molecule for composition information like the glucose, but it is still an unresolved problem that how to detect the subcutaneous glucose concentration by using the MIR-ATR Spectroscopy. In the present paper, we carry out the experiment based on MIR-ATR for the detection of subcutaneous glucose information on both the natural state and the penetration state based on the theoryanalysis of MIR penetration depth. Firstly, collect spectral data of the subcutaneous glucose concentration of human finger on the natural state were collected as the light shined the skin directly, and it was discussed whether the MIR can penetrate the skin to get the information of subcutaneous glucose. On this basis, collect spectral data of the subcutaneous glucose concentration of human finger at the penetration state were collected when the Interstitial fluid is permeated to the surface layer by using low-frequency ultrasound and vacuum, then it analyzed that whether it can detect the glucose-specific information or not. As the two-dimensional correlation spectroscopy has high resolution and good versatility, it is widely used to analyze the inter-molecular reaction and judge the absorption peaks information in many fields including the MIR spectroscopy field, so we choose the Two-dimensional correlation spectroscopy to analyze the information of subcutaneous glucose concentration at the natural state and the penetration state. The experiment result shows that the MIR-ATR spectroscopy can't be applied in the detection of subcutaneous glucose concentrationdirectly, and it is a promising direction to make the Interstitial fluid permeated to the surface layer by the physical methods or chemical methods.

[Application of mid-infrared wavelength tunable laser in glucose determination].

The authors proposed a method of control and stabilization for laser emission wavelengths and power, and presented the mid-infrared wavelength tunable laser with broad emission spectrum band of 9.19-9.77 microm, half wave width of 4 cm(-1), spectral resolution of 2.7 x 10(4) and max power of 800 mW with fluctuation < 0.8% in the present paper. The tunable laser was employed as the light source in combination with ATR sensor for glucose measurement in PBS solution. In our experiments, absorbance at the five laser emission wavelengths, including 1 081, 1 076, 1 051, 1 041 and 1 037 cm(-1) in the 9R and 9P band of the laser emission spectrum, all correlates well with the glucose concentration (R2 > 0.99, SD < 0.0004, P < 0.000 1). Especially, the sensitivity of this laser spectroscopy system is about 4 times as high as that of traditional FTIR spectrometer.

Preparation and characterization of chitosan porous microcarriers for hepatocyte culture.

BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative method for treating liver failure. The core of the BAL system is culturing liver cells in vitro with high density and activity. Microcarrier culture is a mode of high-density culture. We set out to prepare a novel porous microcarrier to improve the activity of liver cells in vitro. METHODS: Chitosan was used to prepare a novel porous spherical microcarrier with interconnected structure. The chitosan porous microcarriers (CPMs) were modified with gelatin to improve their biocompatibility. CPMs were co-cultured with liver cells, HL-7702 (L-02), to evaluate their effect on cell culture. RESULTS: The average size of the CPMs was about 400 µm in diameter and their apertures were less than 30 µm. The pores of the microcarrier were interconnected. After fixation by sodium tripolyphosphate, the structure of the first freeze-dried CPMs was stable. To further improve the biocompatibility, the surface of CPMs was modified with gelatin through chemical crosslinking (GM-CPMs). Comparing the proliferation curves of L-02 cells cultured on simple CPMs, GM-CPMs and tissue culture polystyrene (TCPS, a mode of planar cell culture), the proliferation rates were similar in the first 5 days and the cells proliferated until day 8 in culture with microcarriers. The OD value of liver cells cultured on GM-CPMs was 1.97-fold higher than that on TCPS culture at day 8. Levels of urea and albumin in supernatants of cells cultured on GM-CPMs increased steadily for 8 days, and were clearly higher than those of cells cultured on TCPS (P<0.05). CONCLUSIONS: The novel CPMs were promising microcarriers for hepatocyte culture and the GM-CPM seemed better. Porous microcarrier culture was beneficial for hepatocyte function and activity.

[Induction and activity changes of protein kinase in grape leaves under heat stress].

The type and activity of protein kinase induced and activated by heat stress were studied in leaves of "Jingxiu" grape (Vitis vinifera L. cv. Jingxiu). The results showed that a 52-kD protein kinase was evidently activated by heat stress in 10 to 60 min. Myelin basic protein (MBP) embedded in gel could be phosphorylated by the 52 kD protein kinase. The phosphorylating activity of this kinase was determined by using MBP as the substrate and measuring the products of phosphorylation by autoradiography. The 52 kD protein kinase could not affect histone-III embedded as the substrate in gel and the products of phosphorylation by autoradiography was not displayed. High phosphorylation activity of this protein kinase was found with MBP substrate in solution reaction system. After 60 min heat stress, the activity of this protein kinase reached its maximum value, and then declined rapidly. Compared with control, the activity of protein kinase had no difference when histone-III was used as substrate in reaction system. The activity of this protein kinase was not enhanced by Ca(2+), showing that it was not Ca(2+)-dependent. The tyrosine-specific protein phosphatase (YOP) could significantly inactivate the phosphorylation activity of protein kinase. All results demonstrate that the 52 kD protein kinase activated by heat stress belong to the MAPK family.