Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization.

BACKGROUND: Cytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors. METHODS: Bidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty-one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome-wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate-to-vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10 min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta-GWAS and the UK Biobank, and sample sizes ranged from 69 537 to 472 174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut-off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5 × 10-6 and 5 × 10-8). Inverse-variance weighted, MR-Egger and weighted median were employed to estimate the causality. RESULTS: Twenty-seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin-16), CTACK (cutaneous T-cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet-derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956-0.998] for EWGSOP and 0.933 [0.874-0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995-1.000]) and AWCU10 (1.008 [1.003-1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007-1.019] for EWGSOP and 1.090 [1.041-1.142] for FNIH), AWCU10 (0.990 [0.986-0.994]) and telomere length (0.998 [0.983-0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001-1.063] for EWGSOP), AWCU10 (0.994 [0.988-1.000] and 0.993 [0.988-0.998]) and telomere length (1.006 [1.000-1.012]). PDGFbb may causally relate to AALM (1.016 [1.001-1.030]) and telomere length (1.011 [1.007-1.015]). Reserve MR analyses also proved their unidirectional causal effects. CONCLUSIONS: Twenty-seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

Effect of inflammatory response on joint function after hip fracture in elderly patients: A clinical study.

BACKGROUND: Excellent hip joint function facilitates limb recovery and improves the quality of survival. This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management. AIM: To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients. METHODS: The elderly patients who had hip fracture surgery at our hospital between January 1, 2021, and December 31, 2022 were chosen for this retrospective clinical investigation. Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared. Age, gender, fracture site, surgical technique, laboratory indices, and other variables that could have an impact on postoperative joint function were all included in a univariate study. To further identify independent risk factors affecting postoperative joint function in hip fractures, risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis. In addition to this, we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups. RESULTS: A total of 119 elderly patients with hip fractures were included in this study, of whom 37 were male and 82 were female. The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and complement C1q (C1q) between the fair and excellent joint function groups (P < 0.05). The results of multiple logistic regression analysis showed that IL-6 > 20 pg/mL [(Odds ratio (OR) 3.070, 95%CI: 1.243-7.579], IL-8 > 21.4 pg/ mL (OR 3.827, 95%CI: 1.498-9.773), CRP > 10 mg/L (OR 2.142, 95%CI: 1.020-4.498) and C1q > 233 mg/L (OR 2.339, 95%CI: 1.094-5.004) were independent risk factors for poor joint function after hip fracture surgery (all P < 0.05). CONCLUSION: After hip fractures in older patients, inflammatory variables are risk factors for fair joint function; therefore, early intervention to address these markers is essential to enhance joint function and avoid consequences.

Biomaterials for bone defect repair: Types, mechanisms and effects.

Bone defects or bone discontinuities caused by trauma, infection, tumours and other diseases have led to an increasing demand for bone grafts and biomaterials. Autologous bone grafts, bone grafts with vascular tips, anastomosed vascular bone grafts and autologous bone marrow components are all commonly used in clinical practice, while oversized bone defects require the use of bone tissue engineering-related biomaterials to repair bone defects and promote bone regeneration. Currently, inorganic components such as polysaccharides and bioceramics, as well as a variety of bioactive proteins, metal ions and stem cells can be loaded into hydrogels or 3D printed scaffold materials to achieve better therapeutic results. In this review, we provide an overview of the types of materials, applications, potential mechanisms and current developments in the repair of bone defects.

Causal Roles of Lifestyle, Psychosocial Characteristics, and Sleep Status in Sarcopenia: A Mendelian Randomization Study.

BACKGROUND: Many studies reported that lifestyle, psychosocial characteristics, and sleep status related to sarcopenia, although few studies provided evidence of causal relationships between them. METHODS: The data used in our study were from UK Biobank, FinnGen Release 8, and large genome-wide association study meta-analyses. Two-sample Mendelian randomization was conducted to identify the causal associations of 21 traits of lifestyle, psychosocial characteristics, and sleep status with 6 traits of sarcopenia. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. Risk factor analyses were performed to explore the potential mechanism behind the exposures. RESULTS: Mendelian randomization analyses after adjustment proved the causal roles of coffee intake, education years, smoking, leisure screen time, and moderate-to-vigorous intensity physical activity during leisure time in sarcopenia was proven although providing no significant evidence for causal roles for carbohydrates intake, protein intake, alcohol, and sleep status in sarcopenia. CONCLUSIONS: Our results strongly support that coffee intake, education years, smoking, leisure screen time, and moderate-to-vigorous intensity physical activity during leisure time played significantly causal roles in sarcopenia, which may provide new intervention strategies for preventing the development of sarcopenia.

PCDH7 as the key gene related to the co-occurrence of sarcopenia and osteoporosis.

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis.

Sericin/Nano-Hydroxyapatite Hydrogels Based on Graphene Oxide for Effective Bone Regeneration via Immunomodulation and Osteoinduction.

Background: Immune responses and osteogenesis differentiation induced by implants are crucial for bone tissue regeneration. Consideration of only one of those properties is not sufficient. To investigate the synergistic actions, we designed alginate/graphene oxide/sericin/nanohydroxyapatite (Alg/GO/Ser/nHAP) nanocomposite hydrogels with both osteoimmunomodulatory and osteoinductive activities. This study aimed to explore the effect of hydrogel with osteoimmunomodulatory properties on promoting osteogenesis of bone marrow stem cells (BMSCs). Methods: Alg/GO/Ser/nHAP nanocomposite hydrogel was fabricated and was characterized by SEM, FTIR, XRD, stress-strain, rheology, swelling and degradation. After the impact of sericin on M2 macrophage polarization was identified, the BMSCs viability and adhesion were evaluated by CCK8 assay, live/dead staining, cytoskeleton staining. The cell osteogenic differentiation was observed by ALP/ARS staining, immunofluorescence staining, RT-PCR, and Western blotting, respectively. Rat cranial defect model was used to assess osteoimmunomodulatory effects of scaffolds in vivo by micro­computed tomographic, histological, and immunohistochemical analyses after 8 weeks of healing. Results: In vitro experiments revealed that the hydrogel presented desirable mechanical strength, stability, porosity, and biocompatibility. Significantly, sericin and nHAP appeared to exert synergistic effects on bone regeneration. Sericin was observed to inhibit the immune response by inducing macrophage M2-type polarization to create a positive osteoimmune microenvironment, contributing to improving osseointegration at the bone-implant interface to promote osteogenesis. However, the osteogenic differentiation in rat BMSCs was further enhanced by combining nHAP and sericin in the nanocomposite hydrogel. Eventually, the hydrogel was implanted into the rat cranial defect model, assisting in the reduction of local inflammation and efficient bone regeneration. Conclusion: The nanocomposite hydrogel stimulated bone formation by the synergistic effects of immunomodulation of macrophage polarization by sericin and direct osteogenic induction by nHAP, demonstrating that such a scaffold that modulates the osteoimmune microenvironment to promote osteogenesis is a promising approach for the development of bone tissue engineering implants in the future.

The prognostic value of retinol binding protein in geriatric hip fractures after surgeries: A propensity score matching and 1-year follow-up study.

BACKGROUND: We aimed to explore the predictive value of retinol binding protein (RBP) for outcomes of hip fractures. METHODS: Patients with hip fractures who underwent hip surgeries between December 2017 and February 2021 and met the inclusion criteria were analyzed. Propensity score matching was used to reduce the bias of co-factors and ROC curves based on matched populations were created to determine the optimal cutoff point of RBP. The outcomes between patients with low levels of RBP and high levels of RBP were compared. RESULTS: Four hundred eighty patients were enrolled in this study and 69 patients died within one year. After a 1:1 PSM, patients with more than 1-year survival had significantly higher RBP (p = 0.013) than those who died within one year, as well as patients divided by 6-months survival (p = 0.012). Logistics analysis showed that low RBP may be an independent risk factor for 3-month survival, 6-month survival, 1-year survival, and 3-month free walking ability. CONCLUSION: RBP may be associated with the survival and 3-month walking abilities of patients with hip fractures.

Pd-Loaded Cellulose NanoSponge as a Heterogeneous Catalyst for Suzuki-Miyaura Coupling Reactions.

The (eco)design and synthesis of durable heterogeneous catalysts starting from renewable sources derived from biomass waste represents an important step for reducing environmental impacts of organic transformations. Herein, we report the efficient loading of Pd(II) ions on an eco-safe cellulose-based organic support (CNS), obtained by thermal cross-linking between TEMPO-oxidized cellulose nanofibers and branched polyethyleneimine in the presence of citric acid. A 22.7% w/w Pd-loading on CNS was determined by the ICP-OES technique, while the metal distribution on the xerogel was evidenced by SEM-EDS analysis. XPS analysis confirmed the direct chelation of Pd(II) ions by means of the high number of amino groups present in the network, so that further functionalization of the support with specific ligands was not necessary. The new composite turned to be an efficient heterogeneous pre-catalyst for promoting Suzuki-Miyaura coupling reactions between aryl halides and phenyl boronic acid in water, obtaining yields higher than 90% in 30 min, by operating in a microwave reactor at 100 °C and with just 2% w/w of CNS-Pd catalyst with respect to aryl halides (4.5‱ for Pd). At the end of first reaction cycle, Pd(II) ions on the support resulted in being reduced to Pd(0) while maintaining the same catalytic efficiency. In fact, no leaching was observed at the end of reactions, and five cycles of recycling and reusing of CNS-Pd catalyst provided excellent results in terms of yields and selectivity in the desired products.

Prealbumin as a nutrition status indicator may be associated with outcomes of geriatric hip fractures: a propensity score matching and 1-year follow-up study.

AIM: Nutrition status may affect bone metabolism and regeneration in the elderly. However, few studies reported a sensitive nutrition indicator or evaluation tool for geriatric hip fractures. This study aimed to explore if prealbumin (PAB), a critical nutrition-related protein, is related to the prognosis of hip fractures. METHODS: Patients with hip fractures who met the inclusion criteria were included in our study. Geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) were calculated. Propensity score matching (PSM) was used to reduce the influence of confounding factors and ROC curves were conducted to explore the optimal cutoff points of PAB and to compare the prognostic value between GNRI, PNI, and PAB. Then Cox and Logistics analyses were performed to identify the relation between PAB and outcomes of hip fractures. RESULTS: Out of the 546 patients enrolled in this study, 91 patients died within one year. After a 1:1 PSM, the patients with less than 1-year survival had significantly lower PAB (p < 0.001) than those who were still alive at one year. ROC curves showed that the PAB may sensitively predict 6-month survival (AUROC: 0.695), 1-year survival (AUROC: 0.696), and 1-year-free walking ability (AUROC: 0.642). Logistics analysis showed that low PAB may be an independent risk factor for survival and 1-year-free walking ability. CONCLUSION: Low levels of PAB may be associated with poor survival and walking abilities of older patients after surgery for hip fracture.

The paradoxical relation between serum uric acid and outcomes of hip fracture in older patients after surgery: A 1-year follow-up study.

BACKGROUND: The relation between serum uric acid and bone metabolism has been reported in many studies, but few studies have focused on serum uric acid and fracture rehabilitation. We aimed to explore the potential relationships between serum uric acid and outcomes of hip fractures. METHODS: A total of 742 patients with hip fractures who underwent surgeries between December 2017 and February 2021 and met the inclusion criteria were included. The data of male and female patients were analyzed separately. Cox models with different adjusted forms were performed to explore the potential risk factors, and restricted cubic splines were used to determine the nonlinear relationships between serum uric acid and outcomes and optimal cutoff points of serum uric acid. Then, the outcomes were analyzed in the groups divided by cutoff points mentioned above, as well as groups divided by the diagnosis of hyperuricemia or gout. RESULTS: Cox analysis showed that hyperuricemia or gout was associated with increased death risk, and a typical J-shaped curve was observed in the restricted cubic spline. For male patients, a serum uric acid of high level may relate to a high risk of 6-month (P = .008) and 1-year (P = .016) mortality, and a serum uric acid of low level may predict a poor 6-month free walking ability. For female patients, both a serum uric acid of high level and low level were associated with poor 1-year survival (all P < .05), and a serum uric acid of high level may relate to poor 6-month (P = .001) and 1-year (P = .001) free walking ability. CONCLUSION: Patients with hyperuricemia or gout or patients with high and low levels of serum uric acid may face poor outcomes of hip fractures.

Superoxide Dismutase and Glutathione Reductase as Indicators of Oxidative Stress Levels May Relate to Geriatric Hip Fractures' Survival and Walking Ability: A Propensity Score Matching Study.

Background: Oxidative stress status may affect bone metabolism and regeneration. However, few studies reported whether oxidative stress could impact the outcomes of hip fractures. This study aimed to explore if superoxide dismutase and glutathione reductase, the critical antioxidant enzymes, correlated with the prognosis of hip fractures. Methods: Patients with hip fractures were extracted from our database, and those who met the inclusion criteria were analyzed. Propensity score matching was used to reduce the influence of confounding factors, and ROC curves based on matched populations were created to determine the optimal cutoff points of SOD and GR. Then, outcomes between SOD or GR and outcomes of hip fractures were compared. Results: Out of 301 patients enrolled in this study, 50 patients died within one year. After a 1:1 PSM, the patients with less than 1-year survival had significantly lower SOD (p = 0.026) and GR (p = 0.021) than those who were still alive at one year. Logistics analysis showed that low SOD and low GR may be independent risk factors for 6-month survival, 1-year survival, 6-month free walking ability, and 1-year free walking ability. Conclusion: SOD and GR may be the independent risk factors for survival and walking abilities of hip fractures.

High serum levels of ferritin may predict poor survival and walking ability for patients with hip fractures: a propensity score matching study.

Aim: To identify the relationship between ferritin and outcomes for patients with hip fractures. Patients & methods: All patients with hip fractures presenting between May 2017 and January 2021 were included. Univariate and multivariate analyses were performed to determine the risk factors for 1-year survival. Propensity score matching (PSM) was performed for groups divided by ferritin levels. Results: A total of 165 patients were included of whom 28 died during the first year after surgery. Ferritin levels differed significantly between groups divided by 1-year survival. High ferritin (≥308.5 ng/ml) was related to poor 1-year survival and 6-month and 1-year independent walking rate. Conclusion: High ferritin (≥308.5 ng/ml) may predict poor survival and free-walking abilities after surgery for patients with hip fractures.