A novel extracellular vesicles production system harnessing matrix homeostasis and macrophage reprogramming mitigates osteoarthritis.

Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Variety-dependent responses of common tobacco with differential cadmium resistance: Cadmium uptake and distribution, antioxidative activity, and gene expression.

Cadmium (Cd), which accumulates in tobacco leaves, enters the human body through inhalation of smoke, causing harmful effects on health. Therefore, identifying the pivotal factors that govern the absorption and resistance of Cd in tobacco is crucial for mitigating the harmful impact of Cd. In the present study, four different Cd-sensitive varieties, namely, ZhongChuan208 (ZC) with resistance, ZhongYan100 (ZY), K326 with moderate resistance, and YunYan87 (YY) with sensitivity, were cultivated in hydroponic with different Cd concentrations (20 µM, 40 µM, 60 µM and 80 µM). The results indicated that plant growth was significantly decreased by Cd. Irrespective of the Cd concentration, ZC exhibited the highest biomass, while YY had the lowest biomass; ZY and K326 showed intermediate levels. Enzymatic (APX, CAT, POD) and nonenzymatic antioxidant (Pro, GSH) systems showed notable variations among varieties. The multifactor analysis suggested that the ZC and ZY varieties, with higher levels of Pro and GSH content, contribute to a decrease in the levels of MDA and ROS. Among all the Cd concentrations, ZC exhibited the lowest Cd accumulation, while YY showed the highest. Additionally, there were significant differences observed in Cd distribution and translocation factors among the four different varieties. In terms of Cd distribution, cell wall Cd accounted for the highest proportion of total Cd, and organelles had the lowest proportion. Among the varieties, ZC showed lower Cd levels in the cell wall, soluble fraction, and organelles. Conversely, YY exhibited the highest Cd accumulation in all tissues; K326 and ZY had intermediate levels. Translocation factors (TF) varied among the varieties under Cd stress, with ZC and ZY showing lower TF compared to YY and K326. This phenomenon mainly attributed to regulation of the NtNramp3 and NtNramp5 genes, which are responsible for the absorption and transport of Cd. This study provides a theoretical foundation for the selection and breeding of tobacco varieties that are resistant to or accumulate less Cd.

Effect and mechanism of nano-materials on plant resistance to cadmium toxicity: A review.

Cadmium (Cd), one of the most toxic heavy metals, has been extensively studied by environmental scientists because of its detrimental effects on plants, animals, and humans. Increased industrial activity has led to environmental contamination with Cd. Cadmium can enter the food chain and pose a potential human health risk. Therefore, reducing the accumulation of Cd in plant species and enhancing their detoxification abilities are crucial for remediating heavy metal pollution in contaminated areas. One innovative technique is nano-phytoremediation, which employs nanomaterials ranging from 1 to 100 nm in size to mitigate the accumulation and detrimental effects of Cd on plants. Although extensive research has been conducted on using nanomaterials to mitigate Cd toxicity in plants, it is important to note that the mechanism of action varies depending on factors such as plant species, level of Cd concentration, and type of nanomaterials employed. This review aimed to consolidate and organize existing data, providing a comprehensive overview of the effects and mechanisms of nanomaterials in enhancing plant resistance to Cd. In particular, its deep excavation the mechanisms of detoxification heavy metals of nanomaterials by plants, including regulating Cd uptake and distribution, enhancing antioxidant capacity, regulating gene expression, and regulating physiological metabolism. In addition, this study provides insights into future research directions in this field.

Flavonoid compound breviscapine suppresses human osteosarcoma Saos-2 progression property and induces apoptosis by regulating mitochondria-dependent pathway.

This study was aimed to investigate the ability of a flavonoid compound breviscapine (BVP) to suppress growth and elicit apoptosis in human osteosarcoma (OS) Saos-2 cells. The cells were cultured in vitro and treated with three concentrations of BVP (80, 160, and 320 µg/ml). Moreover, C57 mice were injected with Saos-2 cells to establish a subcutaneous xenograft model, and they were subsequently treated with three doses of BVP via intraperitoneal injection. The viability of the cells was examined by the Cell Counting Kit-8 method. The apoptotic cells were assessed by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The tumor volume and weight were monitored from day 3 through day 21 after the last injection. The expression of bax, bcl-2, and cytochrome c (cyt c) mRNA was detected by a real-time polymerase chain reaction. The protein levels of bax, bcl-2, cyt c, caspase 3, and caspase 9 were evaluated by Western blot. The expression and distribution of bcl-2 and bax in tissues were detected by immunohistochemistry. Compared with the control group, BVP treatment inhibited cell proliferation and induced apoptosis of Saos-2 cells in vitro. Consistently, treatment of mice bearing transplanted tumors with BVP suppressed the growth of OS tumors and promoted cell apoptosis; it also reduced tumor volume and weight. Mechanistically, BVP-induced apoptosis was mediated by the mitochondria-dependent pathway, as evidenced by the increased expression of bax and cyt c and the decreased expression of bcl-2, as well as activation of caspase 9 and caspase 3 in vitro and in vitro. Collectively, BVP inhibits growth and promotes apoptosis of OS by activating the mitochondrial apoptosis pathway.

Efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion: a comparative study.

BACKGROUND: The purpose of this study was to investigate the efficacy of gelatin sponge impregnated with ropivacaine on postoperative pain after transforaminal lumbar interbody fusion (TLIF) in patients with lumbar degenerative diseases. METHODS: We retrospectively reviewed patients who underwent TLIF in our department between August 2018 and January 2020. Patients were divided to ropivacaine group and saline group. A ropivacaine group whom received gelatin sponge impregnated with ropivacaine during operation, and a saline group whom were intraoperatively administered by gelatin sponge impregnated with saline. The two groups were compared in reference to postoperative hospital stay, postoperative complications and visual analog scale (VAS) scores. The consumption of postoperative diclofenac sodium suppository use was also recorded. The Oswestry Disability Index (ODI) scores and Japanese Orthopedic Association (JOA) scores were used for functional evaluation at 1 year postoperatively. RESULT: A total of 127 patients were evaluated in this retrospective study. The mean postoperative hospital stay in the ropivacaine group was significantly lower than saline group. The VAS score was significantly lower in patients receiving gelatin sponge impregnated with ropivacaine as compared with patients in saline group on postoperative day 1, 2, 3 and 4. The number of patients who need the administration of diclofenac sodium suppository and the mean consumption of postoperative diclofenac sodium suppository was significantly lower in the ropivacaine group as compared with saline group. CONCLUSION: The application of gelatin sponge impregnated with ropivacaine around the nerve root in patients undergoing TLIF can effectively control the postoperative pain and reduce postoperative hospital stay.

Enhanced osteogenesis of bone marrow stem cells cultured on hydroxyapatite/collagen I scaffold in the presence of low-frequency magnetic field.

As a non-invasive biophysical therapy, electromagnetic fields (EMF) have been widely used to promote the healing of fractures. In the present study, hydroxyapatite/collagen I (HAC) loaded with rabbit bone marrow mesenchymal stem cells (MSCs) were cultured in a dynamic perfusion bioreactor and exposed to EMF of 15 Hz/1mT. Osteogenic differentiation of the seeded cells was analyzed through the evaluation of ALP activity and osteogenesis-related genes expression in vitro. The in vivo osteogenesis efficacy of the cell laden HAC constructs treated with/without EMF was evaluated through a rabbit femur condyle defect model. The results showed that EMF of 15 Hz/1mT could enhance the osteogenic differentiation of the cells seeded on HAC scaffold. Furthermore, the in vivo experiments demonstrated that EMF exposure could promote bone regeneration within the defect and bone integration between the graft and host bone. Taking together, the MSCs seeded HAC scaffold combined with EMF exposure could be a promising approach for bone tissue engineering.

circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis.

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

Abdominal Fat is a Reliable Indicator of Lumbar Intervertebral Disc Degeneration than Body Mass Index.

OBJECTIVE: The objective of this study was to determine whether abdominal fat status correlates with low back pain (LBP) and lumbar intervertebral disc degeneration (IVDD) and to identify a new anthropometric index to predict the likelihood of developing LBP. METHODS: Patients with chronic low back pain admitted to the Affiliated Hospital of Southwest Medical University from June 2022 to May 2023 were collected as the experimental group. Volunteers without LBP from June 2022 to May 2023 were also recruited as the control group. They underwent lumbar spine magnetic resonance imaging and had their body mass index (BMI) measured. Abdominal parameters were measured on T2-weighted median sagittal magnetic resonance imaging at the L3/4 level: abdominal diameter, sagittal abdominal diameter (SAD), and subcutaneous abdominal fat thickness (SAFT). Each lumbar IVDD was assessed using the Pfirrmann grading system. The differences in abdominal parameters and BMI between the experimental and control groups were compared, and the correlations between abdominal parameters, BMI, LBP, and IVDD were analyzed. RESULTS: Abdominal diameter, SAD, and SAFT had moderate-to-strong correlations with BMI. SAD was significantly associated with severe IVDD at L4-L5 and L5-S1 levels with odds ratio of 3.201 (95% confidence interval [CI]: 1.850-5.539, P < 0.001) and 1.596 (95% CI: 1.072-2.378, P = 0.021), respectively. BMI had no significant association with severe IVDD. In women, SAFT and BMI were significantly correlated with LBP; in men, only SAFT was significantly correlated with LBP. Appropriate cutoff values for men and women were 1.52 cm (area under the curve = 0.702, 95% CI: 0.615-0.789, P < 0.001) and 1.97 cm (area under the curve = 0.740, 95% CI: 0.662-0.818, P < 0.001), respectively. Men and women with SAFT of >1.52 cm and >1.97 cm, respectively, had significantly higher rates of LBP. CONCLUSIONS: SAD could predict severe IVDD better than BMI. SAFT is a better predictor of LBP than BMI, especially in men, and reliably distinguished patients with LBP from asymptomatic subjects with reliable cutoff values for men and women.

Comparison of the Clinical Efficacy and Bone Cement Distribution Difference Between Kummell's Disease and Osteoporotic Vertebral Compression Fracture After Percutaneous Kyphoplasty.

BACKGROUND: Kummell's disease (KD) and osteoporotic vertebral compression fracture (OVCF) are commonly found in patients with osteoporosis. Several studies have been conducted on bone cement distribution in OVCF or KD; a comparison between the 2 diseases is rarely reported. OBJECTIVES: To compare the clinical efficacy and bone cement distribution difference between KD and OVCFs after percutaneous kyphoplasty (PKP). STUDY DESIGN: This was a retrospective, nonrandomized controlled study. SETTING: Department of Orthopedics from an affiliated hospital. METHODS: From January 2018 to December 2020, 61 patients who underwent PKP surgery for single KD or OVCF and met the inclusion criteria were retrospectively reviewed. All patients were assigned to 2 groups: the KD group and the OVCF group. Clinical and radiologic characteristics, including the bone cement volume, leakage, bone cement dispersion scale, anterior vertebral height (AVH), median vertebral height (MVH), posterior vertebral height (PVH), Cobb angle and Visual Analog Scale (VAS) were analyzed and compared using Mimics three-dimensional (3D) reconstruction images and 3D reconstruction computed tomography, preoperatively, postoperatively, and 2 years after the operation, respectively. The correlations between the bone cement dispersion scale and the VH improvement rate (VHIR), VH change rate (VHCR), VAS improvement rate (VASIR), and follow-up VAS improvement rate (f-VASIR) were also evaluated. RESULTS: The mean follow-up time was 24.0 months. Postoperative VH, Cobb angle, vertebra volume, and VAS score were significantly improved in the 2 groups (P < 0.05). There was no statistical difference in postoperative parameters between the 2 groups. While a strong positive correlation between VHIR and bone cement dispersion scale was observed in the OVCF group (P < 0.01), no significant correlation between VHIR and bone cement dispersion scale was found in the KD group. There was no correlation between VASIR and bone cement dispersion scale in both groups. Compared with postoperation, VH was lower in both groups in later follow-up, and the difference between the 2 groups was statistically significant (P < 0.05). VH, VAS, f-VASIR, and VHCR had a worse manifestation in the KD group than in the OVCF group. However, no significant correlation was found between VHCR, f-VASIR, and bone cement dispersion scale in the 2 groups. LIMITATIONS: This study was limited by the non-randomized design, small sample size, and lack of a comprehensive follow-up period. CONCLUSIONS: Although there was no significant difference in the bone cement distribution and early clinical efficacy between KD and OVCF patients under the same surgical plan and surgeon, OVCF patients exhibited better long-term radiologic and clinical outcomes.

Aquaporin mediated silicon-enhanced root hydraulic conductance is benefit to cadmium dilution in tobacco seedlings.

Numerous studies shown that silicon (Si) enhanced plants' resistance to cadmium (Cd). Most studies primarily focused on investigating the impact of Si on Cd accumulation. However, there is a lack of how Si enhanced Cd resistance through regulation of water balance. The study demonstrated that Si had a greater impact on increasing fresh weight compared to dry weight under Cd stress. This effect was mainly attributed to Si enhanced plant relative water content (RWC). Plant water content depends on the dynamic balance of water loss and water uptake. Our findings revealed that Si increased transpiration rate and stomatal conductance, leading to higher water loss. This, in turn, negatively impacted water content. The increased water content caused by Si could ascribe to improve root water uptake. The Si treatment significantly increased root hydraulic conductance (Lpr) by 131 % under Cd stress. This enhancement was attributed to Si upregulation genes expression of NtPIP1;1, NtPIP1;2, NtPIP1;3, and NtPIP2;1. Through meticulously designed scientific experiments, this study showed that Si enhanced AQP activity, leading to increased water content that diluted Cd concentration and ultimately improved plant Cd resistance. These findings offered fresh insights into the role of Si in bolstering plant resistance to Cd.

Tizoxanide as a novel theraputic candidate for osteoarthritis.

Osteoarthritis (OA) is a frequently seen degenerative joint disease in the elderly. Its pathogenesis is highly related to the local inflammatory reaction and autophagy. Tizoxanide (Tiz), the main active metabolite of nitazoxanide, has proved its anti-inflammatory properties in several diseases. However, the exact role of Tiz in OA remains to explore. In this study, we investigated the anti-arthritic effects and the underlying molecular mechanisms of Tiz on rat OA. The results showed that Tiz could attenuate the IL-1ß-induced inflammatory disorders, cartilage matrix damage and autophagy reduction in rat chondrocytes. Moreover, employment of autophagy inhibitor 3-methyladenine (3-MA) could antagonize the protective effects of Tiz in IL-1ß-treated rat chondrocytes. Additionally, Tiz also inhibited the IL-1ß-induced PI3K/AKT/mTOR and P38/JNK phosphorylation in chondrocytes. In vivo, intra-articular injection of Tiz could significantly alleviate the progression of cartilage damage in rat OA model. Briefly, our study demonstrated the therapeutic potential of Tiz in OA, suggesting that Tiz administration might serve as a promising strategy in OA therapy.

[Preparation and properties of a new artificial bone composite material].

Objective: To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/ß-tricalcium phosphate (ß-TCP) material (hereinafter referred to as composite material). Methods: Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the ß-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and ß-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ ß-TCP composite material. The α-CSH/ß-TCP composite material prepared with α-CSH, ß-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity. Results: The HA/α-CSH/ß-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 µm. When the content of ß-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/ß-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/ß-TCP composite material ranged from 0 to 1, without cytotoxicity. Conclusion: The HA/α-CSH/ß-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Increased Risk of Rheumatoid Arthritis in Patients With Asthma: A Genetic Association Study Using Two-Sample Mendelian Randomization Analysis.

OBJECTIVE: Observational studies have explored the association between asthma and some types of arthritis, including rheumatoid arthritis and osteoarthritis, but the results are largely contradictory. We aimed to investigate the causal effects of asthma on arthritis, including osteoarthritis, rheumatoid arthritis, gout, and ankylosing spondylitis. METHODS: Two-sample Mendelian randomization (MR) analysis was used to investigate the causal effects of asthma on each arthritis. The genetic instruments for asthma were obtained from a large genome-wide association study of asthma. The inverse-variance weighted (IVW) method was used as the main analysis of MR. Bonferroni-adjusted P value threshold was used to account for multiple comparisons. RESULTS: MR-IVW analysis suggested that adult-onset asthma (AOA) was associated with increased risk of rheumatoid arthritis. The odds ratio for rheumatoid arthritis associated with AOA and childhood-onset asthma (COA) were 1.018 (95% confidence interval [95% CI], 1.011-1.025; P < 0.001) and 1.006 (95% CI 1.001-1.012; P = 0.046), respectively. For osteoarthritis, gout, or ankylosing spondylitis, all the MR analyses showed no significant causal effects of AOA or COA on them. We also performed a reverse MR analysis to explore the causal effects of rheumatoid on all asthma, allergic asthma, or nonallergic asthma and found no significant causal effects on them. CONCLUSION: Genetically predicted AOA predisposes patients to an increased risk of rheumatoid arthritis but has no causal effects on osteoarthritis, gout, and ankylosing spondylitis. The result of COA on rheumatoid arthritis is suggestive of potential causal relationship but needs to be confirmed in further studies.

Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits.

BACKGROUND: Cartilage damage is a common medical issue in clinical practice. Complete cartilage repair remains a significant challenge owing to the inferior quality of regenerative tissue. Safe and non-invasive magnetic therapy combined with tissue engineering to repair cartilage may be a promising breakthrough. METHODS: In this study, a composite scaffold made of Hydroxyapatite-Collagen type-I (HAC) and PLGA-PEG-PLGA thermogel was produced to match the cartilage and subchondral layers in osteochondral defects, respectively. Bone marrow mesenchymal stem cells (BMSC) encapsulated in the thermogel were stimulated by an electromagnetic field (EMF). Effect of EMF on the proliferation and chondrogenic differentiation potential was evaluated in vitro. 4 mm femoral condyle defect was constructed in rabbits. The scaffolds loaded with BMSCs were implanted into the defects with or without EMF treatment. Effects of the combination treatment of the EMF and composite scaffold on rabbit osteochondral defect was detected in vivo. RESULTS: In vitro experiments showed that EMF could promote proliferation and chondrogenic differentiation of BMSCs partly by activating the PI3K/AKT/mTOR and Wnt1/LRP6/ß-catenin signaling pathway. In vivo results further confirmed that the scaffold with EMF enhances the repair of osteochondral defects in rabbits, and, in particular, cartilage repair. CONCLUSION: Hydrogel-Hydroxyapatite-Monomeric Collagen type-I scaffold with low-frequency EMF treatment has the potential to enhance osteochondral repair.

Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy.

Osteoarthritis (OA) is a common age-related joint disease. Its development has been generally thought to be associated with inflammation and autophagy. Rhoifolin (ROF), a flavanone extracted from Rhus succedanea, has exhibited prominent anti-oxidative and anti-inflammatory properties in several diseases. However the exact role of ROF in OA remains unclear. Here, we investigated the therapeutic effects as well as the underlying mechanism of ROF on rat OA. Our results indicated that ROF could significantly alleviate the IL-1ß-induced inflammatory responses, cartilage degradation, and autophagy downregulation in rat chondrocytes. Moreover, administration of autophagy inhibitor 3-methyladenine (3-MA) could reverse the anti-inflammatory and anti-cartilage degradation effects of ROF. Furthermore, P38/JNK and PI3K/AKT/mTOR signal pathways were involved in the protective effects of ROF. In vivo, intra-articular injection of ROF could notably ameliorate the cartilage damage in rat OA model. In conclusion, our work elucidated that ROF ameliorated rat OA via regulating autophagy, indicating the potential role of ROF in OA therapy.

Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study.

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1ß-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

Prognostic value of CDCA3 in kidney renal papillary cell carcinoma.

Kidney renal papillary cell carcinoma (KIRP) is a type of low-grade malignant renal cell carcinoma. Huge challenges remain in the treatment of KIRP. Cell division cycle associated 3 (CDCA3) participates in human physiological and pathological processes. However, its role in KIRP has not been established. Here, we evaluated the prognostic value of CDCA3 in KIRP using a comprehensive bioinformatics approach. Data for CDCA3 expression in KIRP were obtained from online database. Different expression genes between high and low CDCA3 expression groups were identified and evaluated by performing Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A gene set enrichment analysis was performed to elucidate the function and pathway differences between the different. Differences in immune cell infiltration between low and high CDCA3 expression groups were analyzed by a single-sample GSEA method for immune cells. A protein-protein interaction network was generated and hub genes were identified. UALCAN was used to analyze associations between the mRNA expression levels of CDCA3 in KIRP tissues with clinicopathologic parameters. The diagnostic efficacy of CDCA3 for KIRP was analyzed by ROC analysis. Logistic regression was used to analyze relationships between the clinicopathological characteristics and CDCA3 expression. Our results indicated that high CDCA3 mRNA expression is significantly associated with some clinicopathologic parameters in KIRP patients High CDCA3 mRNA expression associated with a shorter overall survival, progression-free interval, and disease-special survival. Taken together, CDCA3 is a potential target for the development of anti-KIRP therapeutics and is an efficient prognostic marker.

Low-frequency electromagnetic fields combined with tissue engineering techniques accelerate intervertebral fusion.

BACKGROUND: Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion. METHODS: In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods. RESULTS: BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully. CONCLUSION: In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.

Effects of electromagnetic fields treatment on rat critical-sized calvarial defects with a 3D-printed composite scaffold.

BACKGROUND: Current strategies for craniofacial defect are faced with unmet outcome. Combining 3D-printing with safe, noninvasive magnetic therapy could be a promising breakthrough. METHODS: In this study, polylactic acid/hydroxyapatite (PLA/HA) composite scaffold was fabricated. After seeding rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds, the effects of electromagnetic fields (EMF) on the proliferation and osteogenic differentiation capacity of BMSCs were investigated. Additionally, 6-mm critical-sized calvarial defect was created in rats. BMSC-laden scaffolds were implanted into the defects with or without EMF treatment. RESULTS: Our results showed that PLA/HA composite scaffolds exhibited uniform porous structure, high porosity (~ 70%), suitable compression strength (31.18 ± 4.86 MPa), modulus of elasticity (10.12 ± 1.24 GPa), and excellent cyto-compatibility. The proliferation and osteogenic differentiation capacity of BMSCs cultured on the scaffolds were enhanced with EMF treatment. Mechanistically, EMF exposure functioned partly by activating mitogen-activated protein kinase (MAPK) or MAPK-associated ERK and JNK pathways. In vivo, significantly higher new bone formation and vascularization were observed in groups involving scaffold, BMSCs, and EMF treatment, compared to scaffold alone. Furthermore, after 12 weeks of implanting, craniums in groups including scaffold, BMSCs, and EMF exposure showed the greatest biomechanical properties. CONCLUSION: In conclusion, EMF treatment combined with 3D-printed scaffold has great potential applications in craniofacial regeneration.