Association between serum cotinine and muscle mass: results from NHANES 2011-2018.

PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.

IRF-1-inhibited lncRNA XIST regulated the osteogenic differentiation via miR-450b/FBXW7 axis.

Osteoporosis influences life quality among elder people. Osteoblast dysfunction could cause the occurrence of osteoporosis. LncRNA XIST are involved in the progression of osteoporosis. However, the correlation between IRF-1 and XIST in osteogenic differentiation remains unclear. In the study, Clinical samples were collected for the analysis of XIST level. mRNA and protein levels were detected by RT-qPCR and western blot, respectively. H&E staining was performed to observe the histological changes in mice. Alizarin Red Staining was applied to assess the calcium deposits in hBMSCs. Meanwhile, the relation among XIST, miR-450b and FBXW7 was investigated by dual luciferase assay and ChIP. In vivo model was constructed to assess the impact of XIST in osteoporosis. XIST was found to be upregulated in osteoporosis, and XIST overexpression could inhibit the osteogenic differentiation in hBMSCs. IRF-1 could transcriptionally inhibit the expression of XIST, and XIST could inhibit osteogenic differentiation through binding with miR-450b in hBMSCs. In addition, miR-450b significantly promoted the osteogenic differentiation in hBMSCs via targeting FBXW7. Furthermore, XIST knockdown could inhibit the symptom of osteoporosis in vivo. IRF-1 promoted the osteogenic differentiation via mediation of lncRNA XIST/miR-450b/FBXW7 axis, and this finding might shed novel insights on exploring new ideas against osteoporosis.

Association Between Serum Iron Status and Muscle Mass in Adults: Results From NHANES 2015-2018.

Background: Iron deficiency or overload may contribute to complications associated with diseases, but the link between iron status and skeletal muscle disorder is poorly understood. This study aimed to investigate the relationship between serum iron status, reflected by serum ferritin concentration, and muscle mass in U.S. adults. Methods: We utilized data from National Health and Nutrition Examination Survey (NHANES) 2015-2018 for analysis. Data on serum ferritin, appendicular skeletal muscle mass (ASM), body mass index (BMI) and confounding factors were extracted and analyzed. Multivariate linear regression analyses and smooth curve fittings were employed to investigate the association between serum ferritin and muscle mass. Subgroup analysis based on iron status, age, gender and race were performed. Results: A total of 2,078 participants were included, and divided into iron deficiency (n = 225), normal iron status (n = 1,366), and iron overload (n = 487) groups. Participants with iron overload had significantly lower ASM and appendicular skeletal muscle index (ASMI) (ASM: 19.329 ± 4.879, ASMI: 0.709 ± 0.138) compared to those with iron deficiency (ASM: 22.660 ± 6.789, ASMI: 0.803 ± 0.206) and normal iron status (ASM: 22.235 ± 6.167, ASMI: 0.807 ± 0.201). The serum ferritin was negatively linked with muscle mass after adjusting for potential confounders (ß = -0.0001, 95% CI: -0.0001, -0.0000). When stratified by iron status, the trend test between them remained significant (P for trend: 0.008). Furthermore, subgroup analysis identified a stronger association in men (ß = -0.0001, 95% CI: -0.0002, -0.0001), age ≥ 40 years (ß = -0.0001, 95% CI: -0.0002, -0.0000), non-Hispanic black (ß = -0.0002, 95% CI: -0.0003, -0.0001) and other races (ß = -0.0002, 95% CI: -0.0003, -0.0000). Conclusions: Our study revealed an inverse relationship between serum iron status and muscle mass in adults. This finding improves our understanding of the impact of serum iron status on muscle mass, and sheds new light on the prevention and treatment of muscle loss.

Can prophylactic negative pressure wound therapy improve clinical outcomes in spinal fusion surgery? A meta-analysis.

PURPOSE: Recently negative pressure wound therapy (NPWT) is increasingly being prophylactically used to prevent wound complications in various types of surgeries, but its role in spinal fusion surgery was less well established. This study aimed to evaluate the efficacy of prophylactic NPWT (PNPWT) usage in spinal fusion surgery. METHODS: Following PRISMA guidelines, databases PubMed, Embase and Web of Science were searched for relevant studies. Studies comparing PNPWT with standard wound dressing (SWD) were included and analyzed. The primary outcome was the incidence of surgical site infection, and secondary outcomes were incidence of wound dehiscence, overall wound complication, readmission and reoperation. RESULTS: A total of five studies were included; there were 279 patients in PNPWT group and 715 patients in SWD group. Four studies investigated surgical site infection; the pooled analysis showed a significantly lower incidence of surgical site infection in PNPWT group (OR: 0.399; 95% CI: 0.198, 0.802). Two studies explored wound dehiscence, three studies reported overall wound complication, and there were no significant differences between the two groups ((OR: 0.448; 95% CI: 0.144, 1.389) and (OR: 0.562; 95% CI: 0.296, 1.065), respectively). Two studies evaluated readmission, three studies compared reoperation rate, and the pooled results demonstrated no significant difference between the two groups ((OR: 1.045; 95% CI: 0.536, 2.038) and (OR: 0.979; 95% CI: 0.442, 2.169), respectively). CONCLUSIONS: The current evidence suggested PNPWT could effectively reduce postoperative surgical site infection, but it had no significant benefit on reducing the incidence of wound dehiscence, overall wound complication, readmission and reoperation.

lncRNA MALAT1 promotes osteogenic differentiation through the miR-217/AKT3 axis: A possible strategy to alleviate osteoporosis.

BACKGROUND: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. The present study aimed to investigate the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation in osteoporosis. METHODS: MALAT1 levels were detected by a real-time polymerase chain reaction (RT-qPCR). Moreover, the levels of osteogenic differentiation-related factors (Bmp4, Col1a1 and Spp1) were measured by a RT-qPCR and western blotting. Alkaline phosphatase (ALP) activity was detected using an ALP staining assay. RESULTS: MALAT1 levels were downregulated in hindlimb unloading mice and simulated in microgravity (MG) treated MC3T3-E1 cells. Moreover, MG treatment induced the downregulation of the expression of ALP, BMP4, Col1a1 and Spp1, whereas overexpression of MALAT1 abolished the downregulation. MG also inhibited ALP activity, whereas MALAT1 reversed the effect. Furthermore, miR-217 was identified as a target of MALAT1, and AKT3 was verified as a target of miR-217. Overexpression of miR-217 rescued the promotion of osteogenic differentiation induced by MALAT1 in MG treated cells. Knockdown of AKT3 abolished the facilitation of osteogenic differentiation induced by downregulation of miR-217. CONCLUSIONS: MALAT1 promotes osteogenic differentiation through regulating miR-217/AKT3 axis, suggesting that MALAT1 is a potential target with respect to alleviating osteoporosis.

Can facet joint block be a complementary or alternative therapeutic option for patients with osteoporotic vertebral fractures: a meta-analysis.

BACKGROUND: Recently facet joint block has been increasingly used to relief the residual pain after vertebral augmentation, but whether it can be a complementary or alternative to vertebral augmentation remain largely unknown. Thus, we conducted this meta-analysis to determine the effect of facet joint block in the treatment of osteoporotic vertebral compression fractures (OVCF). METHODS: Following PRISMA statement, a comprehensive literature search through Embase, PubMed, Web of Science, Wanfang Data, China National Knowledge Infrastructure and Chinese BioMedical Literature Database was performed to identify relevant studies. Studies comparing vertebral augmentation combined with facet joint block (combined therapy) with vertebral augmentation, and studies comparing facet joint block with vertebral augmentation were analyzed, respectively. RESULTS: A total of 10 studies were included. There were seven studies comparing combined therapy with vertebral augmentation, the results showed combined therapy was associated with significantly lower visual analog scale (VAS) scores on postoperative day 1, 7, month 1, 3, and lower oswestry disability index (ODI) scores on postoperative day 1, 7, and month 3. There were three studies comparing facet joint block with vertebral augmentation, the results demonstrated vertebral augmentation only provided better analgesia in month 1 after surgery, but it was associated with a higher incidence of refracture. CONCLUSIONS: Current evidence suggested facet joint block might be considered as a complementary to vertebral augmentation in the treatment of OVCF, but it might not be effectively used as an alternative therapy.

Resveratrol Promotes Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Through miR-193a/SIRT7 Axis.

Resveratrol (RES) is a novel dietary phenol compound derived from plants and has been studied extensively for its health benefit and medical potential including osteoporosis. The purpose of this study is to investigate the role of resveratrol in osteoporosis in vivo and in vitro and explore the mechanism of osteogenic differentiation of BMSCs. RT-qPCR, ELISA, and Western blot were used to measure the expression level of miR-193a, SIRT7, and osteogenic markers proteins. The interaction between miR-193a and SIRT7 was validated by dual-luciferase reporter assay. Moreover, MTT assay was conducted to detect cell viability. Alizarin red s staining was used to examine bone formation and calcium deposits. The ovariectomized rat model was set up successfully and HE staining was used to examine femoral trabeculae tissue. Our results showed that miR-193a was overexpressed, while SIRT7 was downregulated in osteoporosis. RES suppressed miR-193a to promote osteogenic differentiation. Mechanically, miR-193a targeted and negative regulated SIRT7. Additionally, it was confirmed that SIRT7 promoted osteogenic differentiation of BMSCs through NF-κB signaling pathway. Further study indicated that RES exerted its beneficial function through miR-193a/SIRT7-mediated NF-κB signaling to alleviate osteoporosis in vivo. Our research suggested that the RES-modulated miR-193a inhibition is responsible for the activation of SIRT7/NF-κB signaling pathway in the process of osteogenic differentiation, providing a novel insight into diagnosis and treatment of osteoporosis.

What are risk factors for subsequent fracture after vertebral augmentation in patients with thoracolumbar osteoporotic vertebral fractures.

BACKGROUND: Due to its unique mechanical characteristics, the incidence of subsequent fracture after vertebral augmentation is higher in thoracolumbar segment, but the causes have not been fully elucidated. This study aimed to comprehensively explore the potential risk factors for subsequent fracture in this region. METHODS: Patients with osteoporotic vertebral fracture in thoracolumbar segment who received vertebral augmentation from January 2019 to December 2020 were retrospectively reviewed. Patients were divided into refracture group and non-refracture group according to the occurrence of refracture. The clinical information, imaging findings (cement distribution, spine sagittal parameters, degree of paraspinal muscle degeneration) and surgery related indicators of the included patients were collected and compared. RESULTS: A total of 109 patients were included, 13 patients in refracture group and 96 patients in non-refracture group. Univariate analysis revealed a significantly higher incidence of previous fracture, intravertebral cleft (IVC) and cement leakage, greater fatty infiltration of psoas (FIPS), fatty infiltration of erector spinae plus multifidus (FIES + MF), correction of body angle (BA), BA restoration rate and vertebral height restoration rate in refracture group. Further binary logistic regression analysis demonstrated previous fracture, IVC, FIPS and BA restoration rate were independent risk factors for subsequent fracture. According to ROC curve analysis, the prediction accuracy of BA restoration rate was the highest (area under the curve was 0.794), and the threshold value was 0.350. CONCLUSIONS: Subsequent fracture might cause by the interplay of multiple risk factors. The previous fracture, IVC, FIPS and BA restoration rate were identified as independent risk factors. When the BA restoration rate exceeded 0.350, refractures were more likely to occur.

USP17 is upregulated in osteosarcoma and promotes cell proliferation, metastasis, and epithelial-mesenchymal transition through stabilizing SMAD4.

USP17 is upregulated in several cancers, indicating that USP17 might play essential functions in tumor development. However, the function of USP17 in osteosarcoma is still unknown. Our work aimed to investigate the function of USP17 in osteosarcoma. We found that the expression of USP17 was upregulated in osteosarcoma tissues and cell lines, including MG-63 and U2OS. Several functional experiments, such as colony formation analysis, Cell Counting Kit-8 assay, wound healing analysis, and transwell assay, showed that USP17 promoted cell proliferation, migration, and invasion. Moreover, we found that USP17 facilitated migration and invasion through promoting epithelial-mesenchymal transition. SMAD4 has been found to regulate epithelial-mesenchymal transition, co-immunopurification, and glutathione S-transferase pull-down analysis demonstrated that USP17 interacted with SMAD4. Furthermore, USP17 stabilized SMAD4 through its deubiquitinase activity. In conclusion, this study shows that USP17 enhances osteosarcoma cell proliferation and invasion through stabilizing SMAD4.

Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker.

Galectin-8 (Gal-8) plays a significant role in normal immunological function as well as in cancer. This lectin contains two carbohydrate recognition domains (CRD) connected by a peptide linker. The N-terminal CRD determines ligand binding specificity, whereas the linker has been proposed to regulate overall Gal-8 function, including multimerization and biological activity. Here, we crystallized the Gal-8 N-terminal CRD with the peptide linker using a crystallization condition that contains Ni2+. The Ni2+ ion was found to be complexed between two CRDs via crystal packing contacts. The coordination between Ni2+ and Asp25 plays an indirect role in determining the structure of ß-strand F0 and in influencing the linker conformation which could not be defined due to its dynamic nature. The linker was also shortened in situ and crystallized under a different condition, leading to a higher resolution structure refined to 1.08 Å. This crystal structure allowed definition of a short portion of the linker interacting with the Gal-8 N-terminal tail via ionic interactions and hydrogen bonds. Observation of two Gal-8 N-terminal CRD structures implies that the N-terminal tail and the linker may influence each other's conformation. In addition, under specific crystallization conditions, glycerol could replace lactose and was observed at the carbohydrate binding site. However, glycerol did not show inhibition activity in hemagglutination assay.

In vivo anticancer and immunomodulating activities of mannogalactoglucan-type polysaccharides from Lentinus edodes (Berkeley) Singer.

There is considerable interest in the potential of mushrooms in modulating the immune system and/or suppressing tumor growth. Among the studied bioactive compounds in mushrooms, polysaccharides are the most important. Nontoxic fungal polysaccharides have a more important role in immunomodulating and antitumor activities which are related to their effects to act of immune effecter cells such as lymphocytes, macrophages, dendritic cells, and natural killer cells involved in the innate and adaptive immunity. Two mannogalactoglucan-type polysaccharides (WPLE-N-2 and WPLE-A0.5-2), purified from the fruiting bodies of Lentinus edodes, were evaluated for their effects on the cellular immune response of Sarcoma 180 (S-180)-bearing mice. Mice were treated with 100 mg/kg body weight of the polysaccharides for 10 days. Significant tumor regressions of the polysaccharide groups' mice were observed compared to the control group. These polysaccharides could induce an increase in nitrite oxide (NO) production in peritoneal macrophages, significantly increase macrophage phagocytosis of tumor-bearing mice and augment concanavalin (ConA) and lipopolysaccharide (LPS)-induced splenocytes proliferation. Our results indicated that immunomodulating activity occurred through host mediation in response to lymphocyte proliferation, macrophage phagocytosis and induction of NO production while the antitumor activity occurred through direct cytotoxicity. Our findings suggest that mannogalactoglucan-type polysaccharides from L. edodes can be explored as novel potential immunostimulants. Our research provides essential data to a better understanding of L. edodes bioactive compounds, especially polysaccharides. Our results also confirm the key role of ß-linkages in the antitumor and immunomodulating effects of polysaccharides.