Summary
Both sarcopenia and low bone mineral density (BMD) have become public health concerns. We found that presarcopenic and/or sarcopenic individuals were more likely to have lower BMD. And this ...relationship has race and sex-specific discrepancy.
Purpose
The purpose of the study was to investigate the racial and gender differences in the relationship between sarcopenia and BMD among older adults.
Methods
Totally, 5476 subjects (mean age = 65.7 ± 6.4) of non-Hispanic White (
n
= 3297), non-Hispanic Black (
n
= 1265), and non-Hispanic Asian (
n
= 914) were analyzed. Sarcopenia was defined according to the revised European consensus on definition and diagnosis of sarcopenia (EWGSOP2). General linear model and multivariable linear regression model were used to examine the relationship between sarcopenia and regional/whole body BMD stratified by race and sex. Adjustments were conducted for physiological, behavioral, and disease factors.
Results
Comparing with normal older participants, presarcopenic and sarcopenic elderly were more likely to have lower BMD. Although the difference was not statistically significant in a few sub-groups, among the three racial groups, the strongest association between sarcopenia and BMD was found in non-Hispanic Black people, followed by non-Hispanic White people and non-Hispanic Asian people. In addition, significant differences of BMD across sarcopenia stages were found in more sub-groups in women than in men after adjusting for covariates.
Conclusions
In this older cohort, sarcopenia is significantly related to low regional/whole-body BMD, and these associations vary by race and sex. Consideration in race and sex is warranted when developing strategies to maintain or minimize BMD loss.
In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of ...progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.
Summary
Peripheral blood monocytes (PBMs) are an important source of precursors of osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that have profound effects on osteoclast ...differentiation, activation, and apoptosis. So PBMs represent a highly valuable and unique working cell model for bone-related study.
Finding an appropriate working cell model for clinical and (epi-)genomic studies of human skeletal disorders is a challenge. Peripheral blood monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells. Particularly, PBMs provide the sole source of osteoclast precursors for adult peripheral skeleton where the bone marrow is normally hematopoietically inactive. PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important for osteoclast differentiation, activation, and apoptosis. Reduced production of PBM cytokines represents a major mechanism for the inhibitory effects of sex hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have been linked to various skeletal disorders/traits, strongly supporting for the biological relevance of PBMs with bone metabolism and disorders. Here, we briefly review the origin and further differentiation of PBMs. In particular, we discuss the close relationship between PBMs and osteoclasts, and highlight the utility of PBMs in study the pathophysiological mechanisms underlying various skeletal disorders.
Summary
The purpose of the study is to investigate the relationship between sarcopenia and body composition and osteoporosis in cohorts of three different races with a total of 17,891 subjects. Lean ...mass and grip strength were positively associated with bone mineral densities (BMDs). Subjects with sarcopenia were two times more likely to have osteoporosis compared with normal subjects.
Introduction
The relationship between sarcopenia and osteoporosis is not totally clear. First, the present study assessed this relationship by using two different definitions for sarcopenia. Second, we examined the associations of body composition (including muscle mass as a major and important component) and muscle strength on regional and whole-body BMDs.
Methods
In total, 17,891 subjects of African American, Caucasian, and Chinese ethnicities were analyzed. Sarcopenia was defined by relative appendicular skeletal muscle mass (RASM) cut points and also by the definition of the European Working Group on Sarcopenia in Older People (low RASM plus low muscle function). Multiple regression analyses were conducted to examine the association of fat mass, lean mass (including muscle mass), and grip strength with regional and whole-body BMDs. Multivariate logistic regression analysis was performed to explore the association between sarcopenia and osteopenia/osteoporosis.
Results
BMDs were positively associated with lean mass and negatively associated with fat mass, after controlling for potential confounders. Grip strength was significantly associated with higher BMDs. Each standard deviation (SD) increase in RASM resulted in a ~37 % reduction in risk of osteopenia/osteoporosis (odds ratio (OR) = 0.63; 95 % confidence interval (CI) = 0.59, 0.66). Subjects with sarcopenia defined by RASM were two times more likely to have osteopenia/osteoporosis compared with the normal subjects (OR = 2.04; 95 % CI = 1.61, 2.60). Similarly, subjects with sarcopenia (low muscle mass and low grip strength) were ~1.8 times more likely to have osteopenia/osteoporosis than normal subjects (OR = 1.87; 95 % CI = 1.09, 3.20).
Conclusions
High lean mass and muscle strength were positively associated with BMDs. Sarcopenia is associated with low BMD and osteoporosis.
Summary
Low bone mineral density (BMD) and osteoporosis have become a public health problem. We found that non-Hispanic white, black, and Asian adults with extremely low education and personal income ...are more likely to have lower BMD. This relationship is gender-specific. These findings are valuable to guide bone health interventions.
Introduction
The evidence is limited regarding the relationship between socioeconomic status (SES) and bone mineral density (BMD) for minority populations in the USA, as well as the relationship between SES and BMD for men. This study explored and examined the relationship between SES and BMD by race/ethnicity and gender.
Methods
Data (
n
= 6568) from the Louisiana Osteoporosis Study (LOS) was examined, including data for non-Hispanic whites (
n
= 4153), non-Hispanic blacks (
n
= 1907), and non-Hispanic Asians (
n
= 508). General linear models were used to estimate the relationship of SES and BMD (total hip and lumbar spine) stratified by race/ethnicity and gender. Adjustments were made for physiological and behavioral factors.
Results
After adjusting for covariates, men with education levels below high school graduate experienced relatively low hip BMD than their counterparts with college or graduate education (
p
< 0.05). In addition, women reporting a personal annual income under $20,000 had relatively low hip and spine BMD than their counterparts with higher income level(s) (
p
< 0.05).
Conclusions
Establishing a conclusive positive or negative association between BMD and SES proved to be difficult. However, individuals who are at an extreme SES disadvantage are the most vulnerable to have relatively low BMD in the study population. Efforts to promote bone health may benefit from focusing on men with low education levels and women with low individual income.
Summary
By adopting the extension approaches of Mendelian randomization, we successfully detected and prioritized the potential causal risk factors for BMD traits, which might provide us novel ...insights for treatment and intervention into bone-related complex traits and diseases.
Introduction
Osteoporosis (OP) is a common metabolic skeletal disease characterized by reduced bone mineral density (BMD). The identified SNPs for BMD can only explain approximately 10% of the variability, and very few causal factors have been identified so far.
Methods
The Mendelian randomization (MR) approach enables us to assess the potential causal effect of a risk factor on the outcome by using genetic IVs. By using extension methods of MR—multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA)—we intend to estimate the causal relationship between fifteen metabolic risk factors for BMD and try to prioritize the most potential causal risk factors for BMD.
Results
Our analysis identified three risk factors T2D, FG, and HCadjBMI for FN BMD; four risk factors FI, T2D, HCadjBMI, and WCadjBMI for FA BMD; and three risk factors FI, T2D, and HDL cholesterol for LS BMD, and all risk factors were causally associated with heel BMD except for triglycerides and WCadjBMI. Consistent with the mvMR results, MR-BMA confirmed those risk factors as top risk factors for each BMD trait individually.
Conclusions
By combining MR approaches, we identified the potential causal risk factors for FN, FA, LS, and heel BMD individually and we also prioritized and ranked the potential causal risk factors for BMD, which might provide us novel insights for treatment and intervention into bone-related complex traits and diseases.
To investigate the effects of chlorogenic acid-enriched extract (CGAE) from Eucommia ulmoides leaf on performance, meat quality, oxidative stability, and fatty acid profile of breast meat in ...heat-stressed broilers, 400 28-day-old male Ross 308 broilers were randomly assigned into 4 groups with 10 replicates per group (10 broilers per replicate). Broilers in the normal group (NOR) were kept at 22 ± 2°C (24 h/D) and fed the basal diet, and the other 3 groups were treated with cyclic heat (34 ± 2°C from 08:00 to 18:00 and 22 ± 2°C from 18:00 to 08:00) and fed the basal diet supplemented with 0 (HT), 500 (CGAE500), and 1,000 mg (CGAE1000) mg of CGAE/kg of diet. The experiment lasted for 14 D. Compared with the HT group, broilers in the NOR and CGAE1000 groups had a higher average daily gain and a lower feed conversion ratio (P < 0.05). CGAE supplementation at 1,000 mg/kg increased pH24 value, a* value and total superoxide dismutase activity and reduced drip loss, cooking loss, L* value and the contents of malondialdehyde and carbonyl in breast meat of heat-stressed broilers (P < 0.05). Broilers in the HT group showed lower mRNA levels of nuclear factor erythroid 2-related factor 2 (P < 0.001), superoxide dismutase (P = 0.004), and catalase (P < 0.001) in breast meat compared with the other groups. CGAE supplementation at 1,000 mg/kg reduced the stearic acid and saturated fatty acids (SFA) contents and increased the dihomo-γ-linolenic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, polyunsaturated fatty acids (PUFA), and n-6 PUFA contents and PUFA:SFA ratio in breast meat of heat-stressed broilers (P < 0.05). In conclusion, CGAE supplementation at 1,000 mg/kg could alleviate the adverse effects of heat stress on growth performance and meat quality and improve oxidative stability and fatty acid profile of breast meat in heat-stressed broilers.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Background and Purpose
Many disparate studies have reported the ambiguous role of hydrogen sulfide (H2S) in cell survival. The present study investigated the effect of H2S on the viability of cancer ...and non‐cancer cells.
Experimental Approach
Cancer and non‐cancer cells were exposed to H2S using sodium hydrosulfide (NaHS) and GYY4137 and cell viability was examined by crystal violet assay. We then examined cancer cellular glycolysis by in vitro enzymatic assays and pH regulator activity. Lastly, intracellular pH (pHi) was determined by ratiometric pHi measurement using BCECF staining.
Key Results
Continuous, but not a single, exposure to H2S decreased cell survival more effectively in cancer cells, as compared to non‐cancer cells. Slow H2S‐releasing donor, GYY4137, significantly increased glycolysis, leading to overproduction of lactate. H2S also decreased anion exchanger and sodium/proton exchanger activity. The combination of increased metabolic acid production and defective pH regulation resulted in an uncontrolled intracellular acidification, leading to cancer cell death. In contrast, no significant intracellular acidification or cell death was observed in non‐cancer cells.
Conclusions and Implications
Low and continuous exposure to H2S targets metabolic processes and pH homeostasis in cancer cells, potentially serving as a novel and selective anti‐cancer strategy.
Summary
In this study, label-free-based quantitative subcellular proteomics integrated with network analysis highlighted several candidate genes including P4HB, ITGB1, CD36, and ACTN1 that may be ...involved in osteoporosis. All of them are predicted as significant membrane proteins with high confidence and enriched in bone-related biological process. The results were further verified in transcriptomic and genomic levels.
Introduction
Osteoporosis is a metabolic bone disease mainly characterized by low bone mineral density (BMD). As the precursors of osteoclasts, peripheral blood monocytes (PBMs) are supported to be important candidates for identifying genes related to osteoporosis. We performed subcellular proteomics study to identify significant membrane proteins that involved in osteoporosis.
Methods
To investigate the association between monocytes, membrane proteins, and osteoporosis, we performed label-free quantitative subcellular proteomics in 59 male subjects with discordant BMD levels, with 30 high vs. 29 low BMD subjects. Subsequently, we performed integrated gene enrichment analysis, functional annotation, and pathway and network analysis based on multiple bioinformatics tools.
Results
A total of 1070 membrane proteins were identified and quantified. By comparing the proteins’ expression level, we found 36 proteins that were differentially expressed between high and low BMD groups. Protein localization prediction supported the notion that the differentially expressed proteins, P4HB (
p
= 0.0021), CD36 (
p
= 0.0104), ACTN1 (
p
= 0.0381), and ITGB1 (
p
= 0.0385), are significant membrane proteins. Functional annotation and pathway and network analysis highlighted that P4HB, ITGB1, CD36, and ACTN1 are enriched in osteoporosis-related pathways and terms including “ECM-receptor interaction,” “calcium ion binding,” “leukocyte transendothelial migration,” and “reduction of cytosolic calcium levels.” Results from transcriptomic and genomic levels provided additional supporting evidences.
Conclusion
Our study strongly supports the significance of the genes P4HB, ITGB1, CD36, and ACTN1 to the etiology of osteoporosis risk.
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