Exploring the causal relationship between inflammatory bowel disease and sarcopenia-related traits: a two-sample Mendelian randomization analysis.

Previous observational studies have shown an association between inflammatory bowel disease (IBD) and sarcopenia. However, the causal relationship between IBD (including ulcerative colitis and Crohn's disease) and sarcopenia remains unclear. Thus, this study investigated whether genetically predicted IBD play a function in the occurrence of sarcopenia using Mendelian randomization (MR) analysis. This study used independent single nucleotide polymorphisms (SNPs) significantly associated with IBD as instrument variables (IVs). Sarcopenia-related components (hand grip strength, walking space, and appendicular lean mass (ALM)) were investigated as outcome factors, with summary-level data regarding these components of sarcopenia obtained from the UK Biobank. The IVW-MR analysis revealed that there were significant negative associations between IBD and hand grip strength (both left and right) as well as ALM. Besides, the results of IVW-MR analysis provided strong evidence of a causal relationship between genetically predicted Crohn's disease and hand grip strength and ALM. However, there were no significant associations found between ulcerative colitis and sarcopenia-related traits. Sensitivity tests confirmed the accuracy and robustness of the above MR analysis. Conclusions: Our MR analysis showed the causal effect of Crohn's disease on hand grip strength and ALM. This suggests that Crohn's disease may be a potential risk factor for sarcopenia.

The concentrations of bone calcium, phosphorus and trace metal elements in elderly patients with intertrochanteric hip fractures.

Introduction: Trace metal elements may play a crucial role in bone mineralization and metabolism. However, the quantification of trace element concentrations in human bone tissue has received little attention. Materials and methods: Bone tissue samples were collected from 55 elderly patients (15 males and 40 females) with intertrochanteric hip fractures. The calcium, phosphorus, manganese, iron, copper, and zinc concentrations in the cortical bone zone, cancellous bone zone, and junction zone between cortical and cancellous bone were determined by energy-dispersive X-ray fluorescence (EDX). The differences in trace element concentrations in the three regions were compared, and the correlation between gender and bone trace element contents of the bones was analyzed using the Kruskal-Wallis's test. The correlation between age, body mass index (BMI), and bone calcium, phosphorus concentrations, and trace elements in three bone zones was determined using Spearman correlation analysis. Results: The Kruskal-Wallis test showed no difference in bone phosphorus concentration among the three regions. In contrast, the difference in the concentrations of bone calcium and four metal elements was statistically significant (P<0.01). In addition, no statistical differences were observed in the concentrations of trace elements among the three regions in elderly male and female patients. Spearman correlation analysis showed a strong negative correlation between bone calcium and phosphorus in three bone regions (r=-0.999, -0.95, -0.998, P < 0.01) and a significant positive correlation between trace metal elements in the cancellous bone zone. In the junction zone, the BMI showed a strong positive correlation with bone calcium content (r=0.347, P=0.009) and a significant negative correlation with phosphorus content (r=-0.349, P=0.009). Conclusion: Bone calcium and phosphorus were the main components of hydroxyapatite, and these two elements accounted for the majority of bone mineral salts. Trace metal elements are essential for bone metabolism and specific synergistic interactions. BMI may be associated with bone calcium and phosphorus contents in elderly patients with osteoporosis.

Association between bone trace elements and osteoporosis in older adults: a cross-sectional study.

Objectives: Metal micronutrients deficiency may be one of the risk factors for the development of osteoporosis. This study aimed to measure the trace element contents in human bone tissue to analyze the relationship between micronutrients and osteoporosis. Design: A cross-sectional survey was performed on data from 51 elderly patients with proximal femoral fracture. Methods: The concentrations of calcium, phosphorus, manganese, iron, copper, and zinc in bone tissue samples from 51 elderly patients with proximal femoral fracture were determined by energy-dispersive X-ray fluorescence (EDX). Subjects were divided into osteoporosis and non-osteoporosis groups according to their bone mineral density (BMD) T-score values. The difference in metal elements concentrations in bone tissue between the two groups was compared, and the role of metal elements in osteoporosis was discussed. Results: There was no statistical difference in age, sex, body mass index (BMI), serum albumin, biochemical blood indices, and bone turnover markers between the two groups. The Mann-Whitney U test was used to compare the difference in metal elements concentrations in bone tissue samples between the two groups. The results showed that manganese, copper, and zinc concentrations in the cancellous bone were significantly higher in the non-osteoporosis group than in the osteoporosis group. Multivariate logistic regression analysis indicated that high bone zinc concentration [odds ratio = 0.26, 95% confidence interval (CI) = 0.075-0.928, p = 0.038] was negatively correlated with osteoporosis. Conclusion: Manganese, copper, and zinc play an essential role in bone mineralization and metabolism. Among them, zinc may be most closely related to osteoporosis and play a key role in bone development and maintenance of bone mass. Therefore, we believe that the design of zinc-rich compounds or nutrients as a new complementary factor to increase the intake of zinc for the elderly could be able to prevent and intervene in the occurrence of osteoporosis in the early stage.

Development and Verification of a Combined Diagnostic Model for Sarcopenia with Random Forest and Artificial Neural Network.

Background: Sarcopenia is a chronic disease characterized by an age-related decline in skeletal muscle mass and function, and diagnosis is challenging owing to the lack of a clear "gold standard" assessment method. Objective: This study is aimed at combining random forest (RF) and artificial neural network (ANN) methods to screen key potential biomarkers and establish an early sarcopenia diagnostic model. Methods: Three gene expression datasets were downloaded and merged by searching the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the merged dataset were identified by R software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Afterward, the STRING database was employed for interaction analysis of the differentially encoded proteins. Then, RF was used to identify key genes from the DEGs, and a sarcopenia diagnostic model was constructed by ANN. Finally, the diagnostic model was assessed using a validation dataset, while its diagnostic performance was evaluated by the area under curve (AUC) value. Results: 107 sarcopenia-related DEGs were identified, and they were mainly enriched in the FoxO and AMPK signaling pathways involved in the molecular pathogenesis of sarcopenia. Thereafter, seven key genes (MT1X, FAM171A1, ZNF415, ARHGAP36, CISD1, ETNPPL, and WISP2) were identified by the RF classifier. The proteins encoded by three of these genes (CISD1, ETNPPL, and WISP2) may be potential biomarkers for sarcopenia. Finally, a diagnostic model for sarcopenia was successfully designed by ANN, achieving an AUC of 0.999 and 0.85 in the training and testing datasets, respectively. Conclusion: We identified several potential genetic biomarkers and successfully developed an early predictive model with high diagnostic performance for sarcopenia. Moreover, our results provide a valuable reference for the early diagnosis and screening of sarcopenia in the future.

Screening Potential Diagnostic Biomarkers for Age-Related Sarcopenia in the Elderly Population by WGCNA and LASSO.

Background: Sarcopenia is a common chronic disease characterized by age-related decline in skeletal muscle mass and function, and the lack of diagnostic biomarkers makes community-based screening problematic. Methods: Three gene expression profiles related with sarcopenia were downloaded and merged by searching the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and eigengenes of a module in the merged dataset were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA), and common genes (CGs) were defined as the intersection of DEGs and eigengenes of a module. CGs were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen the CGs for identifying the diagnostic biomarkers of sarcopenia. Based on the diagnostic biomarkers, we established a novel nomogram model of sarcopenia. At last, we validated the diagnostic biomarkers and evaluated the diagnostic performance of the nomogram model by the area under curve (AUC) value. Results: We screened out 107 DEGs and 788 eigengenes in the turquoise module, and 72 genes were selected as CGs of sarcopenia by intersection. GO analysis showed that CGs were mainly involved in metal ion detoxification and mitochondrial structure, and KEGG analysis revealed that CGs were mainly enriched in the mineral absorption, glucagon signaling pathway, FoxO signaling pathway, insulin signaling pathway, AMPK signaling pathway, and estrogen signaling pathway. Then, six diagnostic biomarkers (ARHGAP36, FAM171A1, GPCPD1, MT1X, ZNF415, and RXRG) were identified by LASSO analysis. Finally, the validation AUC values indicated that the six diagnostic biomarkers had high diagnostic accuracy for sarcopenia. Conclusion: We identified six diagnostic biomarkers with high diagnostic performance, providing new insights into the incidence and progression of sarcopenia in future research.

Effects of Osteocyte Shape on Fluid Flow and Fluid Shear Stress of the Loaded Bone.

This study was conducted to better understand the specific behavior of the intraosseous fluid flow. We calculated the number and distribution of bone canaliculi around the osteocytes based on the varying shapes of osteocytes. We then used these calculated parameters and other bone microstructure data to estimate the anisotropy permeability of the lacunar-canalicular network. Poroelastic finite element models of the osteon were established, and the influence of the osteocyte shape on the fluid flow properties of osteons under an axial displacement load was analyzed. Two types of boundary conditions (BC) that might occur in physiological environments were considered on the cement line of the osteon. BC1 allows free fluid passage from the outer elastic restraint boundary, and BC2 is impermeable and allows no free fluid passage from outer displacement constrained boundary. They both have the same inner boundary conditions that allow fluid to pass through. Changes in the osteocyte shape altered the maximum value of pressure gradient (PG), pore pressure (PP), fluid velocity (FV), and fluid shear stress (FSS) relative to the reference model (spherical osteocytes). The maximum PG, PP, FV, and FSS in BC2 were nearly 100% larger than those in BC1, respectively. It is found that the BC1 was closer to the real physiological environment. The fluid flow along different directions in the elongated osteocyte model was more evident than that in other models, which may have been due to the large difference in permeability along different directions. Changes in osteocyte shape significantly affect the degrees of anisotropy of fluid flow and porous media of the osteon. The model presented in this study can accurately quantify fluid flow in the lacunar-canalicular network.

Association between bone turnover markers, BMD and height loss of cemented vertebrae after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures.

INTRODUCTION: Percutaneous vertebroplasty (PVP) was recently performed for treating patients with osteoporotic vertebral compression fractures (OVCF). However, recompression of cemented vertebra with significant vertebral height loss occurred in the patients after PVP was observed during the follow-up period. The purpose is to explore the risk factors among several potential predictors for the height loss of treated vertebral bodies after PVP in patients with OVCF. METHODS: A study of 93 patients who had undergone PVP between May 1, 2016, and March 1, 2019, at the Spine Center of Huadong Hospital Affiliated to Fudan University was conducted. The fractured vertebral height loss ratio ≥ 15% at final follow-up were defined as cemented vertebra recompression. The following variables were measured and collected: age, gender, body mass index (BMI), bone mineral density (BMD), volume of bone cement injected, bone cement leakage, fractured vertebra segment, contact between bone cement and endplates, serum of calcium and phosphorus, and six kinds of bone turnover markers. RESULTS: Mann-Whitney U test and Univariate Logistic regression analysis showed that the cemented vertebra recompression was correlated with BMD, contact between bone cement and endplates, parathyroid hormone (PTH), and 25-hydroxy vitamin D3 (25-OH-D3). Following multivariate modeling, multiple factors logistic regression elucidated that high BMD (P < 0.001, OR = 0.089) and high level of serum 25-OH-D3 (P = 0.012, OR = 0.877) were negatively correlated with the cemented vertebra recompression after PVP. CONCLUSION: Decreased BMD and lower level of serum 25-OH-D3 might be two critical and significant risk factors for the height loss of cemented vertebrae after PVP.

Icariin-Loaded Hydrogel Regulates Bone Marrow Mesenchymal Stem Cell Chondrogenic Differentiation and Promotes Cartilage Repair in Osteoarthritis.

Intra-articular injection of mesenchymal stem cells is a potential therapeutic strategy for cartilage protection and symptom relief for osteoarthritis (OA). However, controlling chondrogenesis of the implanted cells in the articular cavity remains a challenge. In this study, hydrogels containing different concentrations of icariin were prepared by in situ crosslinking of hyaluronic acid and Poloxamer 407. This injectable and thermoresponsive hydrogel, as a 3D cell culture system, showed good biocompatibility with chondrocytes and bone marrow mesenchymal stem cells (BMSCs), as well as promoted proliferation and chondrogenesis of BMSCs through the Wnt/ß-catenin signaling pathway. Intra-articular injection of this kind of BMSC-loaded composite hydrogel can significantly prevent cartilage destruction by inducing chondrogenic differentiation of BMSCs, and relieve pain through regulating the expression of inflammatory cytokines (e.g., IL-10 and MMP-13) in the OA model. Incorporating BMSCs into this novel icariin-loaded hydrogel indicates a more superior efficacy than the single BMSC injection, which suggests a great potential for its application in OA.

Development and validation of a novel diagnostic model for musculoskeletal aging (sarcopenia) based on cuproptosis-related genes associated with immunity.

OBJECTIVE: Sarcopenia is a geriatric disease characterized by accelerated skeletal muscle mass and function loss due to aging. Cell death plays a pivotal role in the onset and progress of sarcopenia. The purpose of this study was to investigate the role of cuproptosis-related genes (CRGs) and immune infiltration in sarcopenia development. METHODS: Three microarray expression datasets from the Gene Expression Omnibus (GEO) database were merged and batch-corrected by R software to identify differentially expressed genes (DEGs) between old and young skeletal muscles. Subsequently, DEGs were subjected to functional enrichment and gene set enrichment analysis (GSEA) to investigate the roles of DEGs and immune infiltration in the pathogenesis of musculoskeletal aging. Then, ssGSEA was performed to calculate the proportion of immune cells and functions within each muscle sample to analyze the differences between the older and young healthy muscle groups. In order to select candidate CRGs, the correlation between CRGs and immune infiltration was analyzed. Finally, a novel nomogram model of musculoskeletal aging was constructed based on candidate CRGs associated with immunity. Additionally, the diagnostic model based on key CRGs was tested using a validation dataset, and its diagnostic performance was evaluated by the area under curve (AUC) value. RESULTS: 141 DEGs were identified between 45 older samples and 50 young healthy samples. Compared to young healthy muscle tissues, significantly lower infiltration levels of T-regulatory cells were identified in older muscle tissues, while dendritic cells (DCs) and mast cells were relatively higher. Based on the CRGs from seven candidates, a novel model with high prediction efficiency (AUC = 0.856) was established to diagnose and screen for sarcopenia. CONCLUSION: The CRGs associated with immunity may play a vital role in the development of musculoskeletal aging, providing a novel avenue for early diagnosis. Furthermore, immune cell infiltration is essential for the progression of musculoskeletal aging.

Screening of functional monomers and solvents for the molecular imprinting of paclitaxel separation: a theoretical study.

The interactions between the template molecule paclitaxel (PTX) and seven functional monomers containing methacrylic acid (MA), acrolein (AC), 4-vinylbenzoic acid (4VA), acrylonitrile (AN), 2-vinylpyridine (2VP), 2,6-bisacrylamide pyridine (BAP) and methyl methacrylate (MM) were systematically investigated adopting the density functional theory (DFT) method. Moreover, the different binding sites on PTX and solvents embracing chloroform, acetone, ethanol, methanol, and acetonitrile were considered. The calculated solvent energies (ΔEsolvent) and template-monomer binding energies (ΔEb) suggest that the chloroform is the most suitable solvent for the molecular imprinting reaction of PTX among the studied five solvents. Furthermore, from the obtained ΔEb, we can find that the monomer 4VA combining with PTX in the form of the specific intermolecular hydrogen bonds would present the most stable structure among the investigated monomers. These results can provide valuable theoretical guidance for the efficient extraction of PTX by the molecular imprinting technique in experiments. Graphical abstracts.

Loading paclitaxel into porous starch in the form of nanoparticles to improve its dissolution and bioavailability.

In this work, paclitaxel was loaded into porous starch in the form of nanoparticles (PNPS), and the properties of PNPS were investigated by using raw paclitaxel and the system of paclitaxel directly loaded into porous starch (PPS) as control groups. According to the tested results, the drug loading (DL) and encapsulation efficiency (EE) of PNPS were 14.13%±0.27% and 73.92%±0.54%, higher than that of PPS (9.79%±0.31% and 71.17%±0.67%) respectively. Compared with raw paclitaxel and PPS, PNPS exhibited the more prominent dissolution rate and bioavailability, in which the bioavailability of PPS and PNPS were 2.94 and 5.42 times of that of raw paclitaxel respectively. In addition, the IC50 values of raw paclitaxel, PPS and PNPS on Lewis Lung Carcinoma (LLC) cells were 17,703.41±15.76µM, 95.10±5.32µM and 85.68±7.38µM respectively. Furthermore, the residues of acetone in PPS and PNPS were less than the ICH limit for acetone in class III solvents. To summarize, the preparation of PNPS was a potential method to improve the dissolution and bioavailability of paclitaxel.

Effects of nitro- and amino-group on the antioxidant activity of genistein: A theoretical study.

Five novel compounds (Gen-NO2, Gen-2NO2, Gen-NH2, Gen-2NH2 and Gen-6NH2) have been designed via introducing an electron-withdrawing group -NO2 and an electron-donating group -NH2 into the structure of genistein. The effects of -NO2 and -NH2 groups on the antioxidant ability of genistein were investigated via quantum chemistry method in gas and methanol phases. The crucial parameters related to three antioxidant mechanisms were calculated. Moreover, the frontier molecular orbital, natural bond orbital and global descriptive parameters were calculated to evaluate the reactivity of genistein and its derivatives. Calculated results indicate the antioxidant process of genistein and its derivatives inclines to the hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms in gas and methanol phases, respectively. Moreover, introducing -NH2 group into genistein can improve its antioxidant activity owing to the outstanding activities of amino-substituents of genistein, which will provide valuable guidance for the synthesis of new antioxidants experimentally.

Bone Marrow-derived Endothelial Progenitor Cells Are Associated with Bone Mass and Strength.

OBJECTIVE: Blood vessels of bone are thought to influence osteogenesis of bone. No clinical studies have determined whether angiogenesis is related to bone mass and gene expression of growth factors. We compared bone marrow endothelial progenitor cells (EPC), which control angiogenesis of bone in postmenopausal women incurring fragility fracture, with osteoporosis or traumatic fracture with normal bone mass (COM). METHODS: Bone specimens were obtained from age-matched women with osteoporosis or COM. Mononuclear cells were isolated and EPC were detected by flow cytometry. The expression levels of specific genes were measured. Bone mineral density (BMD) was determined, and serum markers of bone turnover also were measured. Differences between OP and COM were assessed with Student t test or Mann-Whitney U test, and correlations were determined using Spearman's correlation. RESULTS: Compared with COM, patients with OP had significantly lower levels of serum osteocalcin, procollagen type-1 N-terminal propeptide, and 25-hydroxy vitamin D, as well as decreased BMD of total hip and femoral neck and fewer bone marrow EPC. Expression levels of vascular endothelial growth factor, angiopoietin-1 (Ang-1), angiopoietin 2 (Ang-2), and the osteoblast-specific genes runt-related transcription factor 2 (RUNX2) and osterix in bone were significantly lower in OP than in COM. We determined that mature EPC were correlated positively with BMD of the femoral neck and total hip, gene expression of Ang-1, RUNX2, and CD31, and negatively with gene expression of receptor activator of nuclear factor-κB ligand and Ang-2. CONCLUSION: Our results demonstrate correlations of bone marrow EPC with bone mass and gene expression of growth factors, which support a hypothesis of crosstalk between angiogenesis and osteogenesis in bone health.

Comparison of the antioxidant effects of carnosic acid and synthetic antioxidants on tara seed oil.

BACKGROUND: In the present study, tara seed oil was obtained by supercritical fluid extraction and used to investigate the antioxidant strength of carnosic acid (CA) compared with conventional synthetic antioxidants. METHODS: The antioxidants were added to the tara seed oil at 0.2 mg of antioxidant per gram of oil. The samples were then submitted to at 60 °C 15 days for an accelerated oxidation process, with samples taken regularly for analysis. After oxidation, the samples were analyzed to determine the peroxide value, thiobarbituric acid reactive substances, conjugated diene content, and free fatty acid content. CA was investigated at three purity levels (CA20, CA60, CA99), and compared with three synthetic antioxidants (butylatedhydroxyanisole, butylatedhydroxytoluene, and tert-butylhydroquinone). RESULTS: The oxidation indicators showed that CA was a strong antioxidant compared to the synthetic antioxidants. The antioxidant activities decreased in the order: tert-butylhydroquinone > CA99 > CA60 > CA20 > butylatedhydroxyanisole > butylatedhydroxytoluene. These results show that CA could be used to replace synthetic antioxidants in oil products, and should be safer for human consumption and the environment.

Improving the skin penetration and antifebrile activity of ibuprofen by preparing nanoparticles using emulsion solvent evaporation method.

Ibuprofen (IBU) is an effective analgesic, non-steroidal anti-inflammatory drug. Unfortunately, oral IBU can cause adverse gastrointestinal drug reactions, such as bleeding and ulcerations, and increases the risk for stomach or intestinal perforations. In this study, IBU nanoparticles (IBU-NPs) were prepared through emulsion solvent evaporation and freeze-drying to improve their solubility. IBU nanoemulsion and nanosuspension were optimized through a single-factor experiment. IBU-NPs with a mean particle size of 216.9±10.7nm were produced under optimum conditions. These IBU-NPs were characterized by using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and residual solvent determination to determine their solvent residue, equilibrium solubility, dissolution rate, in vitro transdermal rate, transdermal bioavailability, and antifebrile experiment for febrile rats. The morphological characteristic of IBU-NPs showed porous clusters. Analysis results indicated that the prepared IBU-NPs have low crystallinity. Residual amounts of ethanol and chloroform were 170 and 9.6ppm, respectively, which were less than the ICH limit for class II. Measurement analysis showed that the IBU-NPs were converted underwent amorphous states after preparation, but the chemical structure of the IBU-NPs was unchanged. Transdermal bioavailability of IBU in the IBU-NP group improved significantly compared with oral and transdermal raw IBU. Furthermore, the IBU-NP transdermal gel exhibited a high and stable cooling rate and a long cooling duration in febrile rats. In comparison with the raw oral IBU and raw IBU transdermal gel, the IBU-NP transdermal gel manifested better efficacy at low and mid doses. Basing from the results, we conclude that IBU-NPs can be applied in transdermal delivery formulations and have potential application value for non-oral administration.

Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty.

BACKGROUND This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). MATERIAL AND METHODS We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and ß-amyloid (Aß) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. RESULTS The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aß expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. CONCLUSIONS CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA.

Brönsted acidic ionic liquid based ultrasound-microwave synergistic extraction of pectin from pomelo peels.

3-Methyl-1-(4-sulfonylbutyl) imidazolium hydrogensulfate, [HO3S(CH2)4mim]HSO4, was applied as an extractant in an ultrasound-microwave synergistic extraction approach to substitute conventional solvent for the extraction of pectin from the albedo part of pomelo peels. The analysis of variance (ANOVA) test and response surface method were employed for the optimization of the extraction conditions. A pectin yield of 328.64±4.19mg/g was achieved using the obtained optimal conditions, which was significantly higher than yields of conventional methods with reference solvents. Pectin samples extracted with [HO3S(CH2)4mim]HSO4 and hydrochloric acid solutions were tested by ANOVA and showed no significant differences in total carbohydrate content and degree of esterification; while galacturonic acid content was significantly different for the pectin from each extraction solvents. The differences revealed from images of atomic force microscopy and scanning electron microscope, Fourier transform infrared spectroscopy, and thermogravimetric analysis suggested the physiochemical properties of pectin could be affected by the extraction solvent. The [HO3S(CH2)4mim]HSO4 proved to be a promising alternative to conventional solvents and the proposed method is efficient for the extraction of pectin from the albedo of pomelo peels.

Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma.

In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients.

Efficacies of surgical treatments based on Harris hip score in elderly patients with femoral neck fracture.

AIM: To compare the efficacies of four surgical treatments, i.e., total hip arthroplasty (THA), internal fixation (IF), hemiarthroplasty (HA), and artificial femoral head replacement (artificial FHR), by performing a network meta-analysis based on Harris hip score (HHS) in elderly patients with femoral neck fracture. METHODS: In strict accordance with specific inclusion and exclusion criteria, randomized controlled trails (RCTs) were screened and selected from a larger group of studies that were retrieved through a comprehensive search of scientific literature databases, further complimented by manual search. The resultant high-quality data from final selected studies were analyzed using Stata 12.0 software. RESULTS: A total of 3680 studies were initially retrieved from database search, and 15 RCTs were eventually incorporated into this meta-analysis, containing 1781 elderly patients who had undergone various surgical treatments for femoral neck fracture (THA group = 604; HA group = 604; IF group = 495; artificial FHR group = 78). Our major result revealed a statistically significant difference in HHS of femoral neck fracture when HA and IF groups were compared with THA. No differences were detected in the HHS of femoral neck fracture undergoing artificial FHR and THA. The surface under the cumulative ranking curves (SUCRA) value of HHS, in elderly patients with femoral neck fracture after surgery, revealed that IF has the highest value. CONCLUSIONS: The current network meta-analysis results suggest that IF is the superlative surgical procedure for femoral neck fracture patients, and IF significantly improves the HHS in femoral neck fracture patients.

Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway.

Naringin exhibits antiinflammatory activity and is shown to induce bone formation. Yet the impact of naringin on inflammation-affected bone marrow-derived mesenchymal stem cell (BM-MSC), a promising tool for the regenerative treatment of bone injury, remained to be investigated. We first cultured and characterized the BM-MSCs in vitro and observe the effects of treatments of TNF-α, naringin, or the combination of both on osteogenic differentiation. TNF-α administered at the concentration of 20 ng/ml results in significant reductions in MSC's cell survival, alkaline phosphatase activity and expressions of two osteogenic genes, Runx2 and Osx. Simultaneous treatment of both TNF-α and naringin is able to rescue such reductions. Further mechanistic studies indicate that TNF-α treatment activates the NF-кB signaling pathway, evidenced by elevated p-IкBα level as well as the increased nuclear fraction of NF-кB subunit, p65. Finally, treatment with both TNF-α and naringin decreases expressions of p-IкBα and nuclear p65, and thus represses NF-кB pathway activated by sole TNF-α treatment. Our findings provide a molecular basis by which naringin restores the TNF-α-induced damage in MSCs and provide novel insights into the application of naringin in the MSC-based treatments for inflammation-induced bone injury.