Biomechanical role of bone grafting for calcaneal fracture fixation in the presence of bone defect: A finite element analysis.

BACKGROUND: The purpose of this study was to compare the biomechanical stress and stability of calcaneal fixations with and without bone defect, before and after bone grafting, through a computational approach. METHODS: A finite element model of foot-ankle complex was reconstructed, impoverished with a Sanders III calcaneal fracture without bone defect and with moderate and severe bone defects. Plate fixations with and without bone grafting were introduced with walking stance simulated. The stress and fragment displacement of the calcaneus were evaluated. FINDINGS: Moderate and severe defect increased the calcaneus stress by 16.11% and 32.51%, respectively and subsequently decreased by 10.76% and 20.78% after bone grafting. The total displacement was increased by 3.99% and 24.26%, respectively by moderate and severe defect, while that of posterior joint facet displacement was 86.66% and 104.44%. The former was decreased by 25.73% and 35.96% after grafting, while that of the latter was reduced by 88.09% and 84.78% for moderate and severe defect, respectively. INTERPRETATION: Our finite element prediction supported that bone grafting for fixation could enhance the stability and reduce the risk of secondary stress fracture in cases of bone defect in calcaneal fracture.

The mitochondrial quality control system: a new target for exercise therapeutic intervention in the treatment of brain insulin resistance-induced neurodegeneration in obesity.

Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer's disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.

The importance of the thickness of femoral lateral wall for treating intertrochanteric fractures: a finite elements analysis.

To explore how the thickness of the femoral lateral wall influences the effectiveness of internal fixation systems used to treat intertrochanteric fractures. CT images of the pelvis and femur of a male adult were used to construct an intertrochanteric fracture model (AO/OTA 31-A2) with various thicknesses of the femoral lateral wall (FLW). Four finite element (FE) models were created with the lateral femoral walls being 10 mm, 20 mm, 30 mm, and 40 mm thick. The fracture models were fixed with a dynamic hip screw (DHS), a proximal femoral nail anti-rotation (PFNA), and a proximal femoral locking compression plate (P-FLCP). A simulated vertical load was applied to the femoral head. The stress and displacement of the implant and femur in each model were recorded for comparison. The FE analysis of the intertrochanteric fracture models showed that the PFNA system could provide better stability than the DHS and P-FLCP with the same thickness of FLW. The FLW provided buttress support to the femoral head and neck when using a DHS and PFNA, and the buttress strength was proportional to the thickness of FLW. The maximum stress in the DHS model was recorded on the DHS plate which accommodated the lag screw. For the PFNA model, the maximum stress appeared at the connection between the nail and blade. In the P-FLCP model, the maximum stresses were highly concentrated at the connection between the cephalic nails and the proximal plate. The thickness of the femoral lateral wall should be considered an important factor when selecting a suitable internal fixation system for intertrochanteric fractures. Based on the FE analysis, intramedullary fixation, such as PFNA, experiences lower stress levels and a moderate displacement in comparison to DHS and P-FCLP when used to treat intertrochanteric fractures.

Do medical alliances truly work? Perspectives on health service utilisation among outpatients with chronic diseases in Shanghai, China.

BACKGROUND: To achieve proper health utilisation among various health institutions and improve primary care capacity, China implemented medical alliance (MA) reform as part of healthcare reforms in 2009. With chronic disease management as the focus and priority of primary health institutions, this study aimed to analyse the specific distribution and trends of outpatient visits to various levels of health institutions (community health centres (CHCs) vs hospitals) in MAs. METHODS: All outpatient data were extracted from the Chuansha MA in Pudong New Area, Shanghai, between 2016 and 2020, and submitted to descriptive analysis, Chi-Square tests and correlation analysis. RESULTS: This article found that outpatients aged >60years visited CHCs more than hospitals for some chronic diseases. The adjusted average costs of outpatients presented upward trends both in hospitals and in CHCs. CONCLUSIONS: The Chuansha MA worked in guiding older outpatients to visit CHCs, but did not control the increasing medical costs. The Shanghai government should further improve medical capability of CHCs to attract all community-dwelling residents at all ages to implement hierarchical diagnosis and treatment systems, as well as make more efforts to control increasing medical costs.

Modified Ni-Nail and C-Nail systems for intra-articular fractures of the calcaneus: A biomechancial study.

OBJECTIVES: We have proposed a novel intramedullary nail (Ni-Nail) by incorporating a sustentaculum tali screw to improve the fixation stability of minimally invasive treatment for calcaneal fractures. This study aimed to evaluate the biomechanical characters of the Ni-Nail system and compare it with traditional C-Nail system. METHODS: A finite element model of a Sanders type-IIIAB calcaneal fracture was reconstructed and fixed using two intramedullary nail systems, which was validated by a cadaver study. A vertical loading of 700 N was applied to the subtalar joint surfaces, and 525 N Achilles tendon tension was applied to the superior border of the Achilles tuberosity. The von Mises stresses and fracture displacements of both fixation models were evaluated. RESULTS: The maximum von Mises stress of the screws of Ni-Nail and C-Nail were 27.92 MPa and 57.42 MPa, respectively, while that of the main nail were 67.44 MPa and 53.01 MPa. In addition, the maximum fracture displacement of the Ni-Nail was larger than that of C-Nail by 15.6% (0.37 mm vs.0.32 mm). CONCLUSIONS: Our static simulation analysis showed that both Ni-Nail and C-Nail demonstrated similar biomechanical stability for calcaneal fixation. The Ni-Nail features a simple structure that is easier to operate and less traumatizing. Future studies may consider to further evaluate the clinical effectiveness by clinical trials and follow-ups.

Lactate Is Answerable for Brain Function and Treating Brain Diseases: Energy Substrates and Signal Molecule.

Research to date has provided novel insights into lactate's positive role in multiple brain functions and several brain diseases. Although notable controversies and discrepancies remain, the neurobiological role and the metabolic mechanisms of brain lactate have now been described. A theoretical framework on the relevance between lactate and brain function and brain diseases is presented. This review begins with the source and route of lactate formation in the brain and food; goes on to uncover the regulatory effect of lactate on brain function; and progresses to gathering the application and concentration variation of lactate in several brain diseases (diabetic encephalopathy, Alzheimer's disease, stroke, traumatic brain injury, and epilepsy) treatment. Finally, the dual role of lactate in the brain is discussed. This review highlights the biological effect of lactate, especially L-lactate, in brain function and disease studies and amplifies our understanding of past research.

Biomechanical Analysis of a Novel Double-Point Fixation Method for Displaced Intra-Articular Calcaneal Fractures.

The development of minimally invasive procedures and implant materials has improved the fixation strength of implants and is less traumatic in surgery. The purpose of this study was to propose a novel "double-point fixation" for calcaneal fractures and compare its biomechanical stability with the traditional "three-point fixation." A three-dimensional finite element foot model with a Sanders type IIIAB calcaneal fracture was developed based on clinical images comprising bones, plantar fascia, ligaments, and encapsulated soft tissue. Double-point and three-point fixation resembled the surgical procedure with a volar distal radius plate and calcaneal locking plate, respectively. The stress distribution, fracture displacement, and change of the Böhler angle and Gissane's angle were estimated by a walking simulation using the model, and the predictions between the double-point and three-point fixation were compared at heel-strike, midstance, and push-off instants. Double-point fixation demonstrated lower bone stress (103.3 vs. 199.4 MPa), but higher implant stress (1,084.0 vs. 577.9 MPa). The model displacement of double-point fixation was higher than that of three-point fixation (3.68 vs. 2.53 mm). The displacement of the posterior joint facet (0.127 vs. 0.150 mm) and the changes of the Böhler angle (0.9° vs. 1.4°) and Gissane's angle (0.7° vs. 0.9°) in double-point fixation were comparably lower. Double-point fixation by volar distal radius plates demonstrated sufficient and favorable fixation stability and a lower risk of postoperative stress fracture, which may potentially serve as a new fixation modality for the treatment of displaced intra-articular calcaneal fractures.

Integrated single-cell multiomics reveals novel immune candidate markers for post-traumatic coagulopathy.

Introduction: Post-traumatic coagulopathy (PTC) is a critical pathology in traumatic brain injury (TBI), however, its potential mechanism is not clear. To explore this in peripheral samples, we integrated single cell RNA-sequencing and T cell repertoire (TCR)-sequencing across a cohort of patients with TBI. Methods: Clinical samples from patients with more brain severity demonstrated overexpression of T cell receptor-encoding genes and less TCR diversity. Results: By mapping TCR clonality, we found patients with PTC have less TCR clones, and the TCR clones are mainly distributed in cytotoxic effector CD8+T cell. In addition, the counts of CD8+ T cell and natural killer (NK) cells are associated with the coagulation parameter by WGCNA, and the granzyme and lectin-like receptor profiles are also decreased in the peripheral blood from TBI patients, suggesting that reduced peripheral CD8+ clonality and cytotoxic profiles may be involved in PTC after TBI. Conclusion: Our work systematically revealed the critical immune status in PTC patients at the single-cell level.

Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.

Lactate mediates multiple cell-intrinsic effects in cancer metabolism in terms of development, maintenance, and metastasis and is often correlated with poor prognosis. Its functions are undertaken as an energy source for neighboring carcinoma cells and serve as a lactormone for oncogenic signaling pathways. Indeed, two isomers of lactate are produced in the Warburg effect: L-lactate and D-lactate. L-lactate is the main end-production of glycolytic fermentation which catalyzes glucose, and tiny D-lactate is fabricated through the glyoxalase system. Their production inevitably affects cancer development and therapy. Here, we systematically review the mechanisms of lactate isomers production, and highlight emerging evidence of the carcinogenic biological effects of lactate and its isomers in cancer. Accordingly, therapy that targets lactate and its metabolism is a promising approach for anticancer treatment.

Fracture mapping of complex intra-articular calcaneal fractures.

BACKGROUND: Intra-articular calcaneal fracture remains challenging to manage. Computed tomography and fracture mapping are useful for the diagnosis and treatment of calcaneal fractures. The aim of the present study was to characterize calcaneal fracture patterns using fracture mapping. METHODS: Sixty-two calcaneal fractures were retrospectively included in the study. For each case, the fracture was simulated reduction manually. The fracture lines and zones of comminution were graphically superimposed onto an intact calcaneal template to identify fracture patterns. Major fracture lines and comminution were assessed by focusing on the posterior joint facet, medial wall, lateral wall, sustentaculum tali, and anterior process. RESULTS: The fracture lines were mostly concentrated on the area anterior to the posterior joint facet and extended medially. The longitudinal lines ran posteriorly from the angle of Gissane, and separated the sustentaculum tali and medial wall from the calcaneal tuberosity. In the lateral wall, the fracture lines extended posteriorly with some branches to the bottom of the calcaneus. No fracture lines passed through the sustentaculum tali. Fracture lines of the posterior tuberosity and anterior process were rare. CONCLUSIONS: Calcaneal fracture lines follow characteristic patterns, which are closely related to the bone structure and fracture mechanism. These fracture patterns will aid clinicians choose surgical approach and fixations in the treatment of calcaneal fractures.

Ring finger protein 152-dependent degradation of TSPAN12 suppresses hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third cause of cancer death in the world, and few molecularly targeted anticancer therapies have been developed to treat it. The E3 ubiquitin ligase RNF152 has been reported to regulate the activity of the mechanistic target of rapamycin complex 1 (mTORC1), induce autophagy and apoptosis. However, the relationship between RNF152 and HCC is unclear. METHODS: Transcriptome RNA-sequencing data of HCC samples and normal tissues were used to detect the mRNA expression of RNF152. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to determine the transcriptional regulation of RNF152 in HCC by FoxO1. RNAi, cell proliferation, colony formation and transwell assays were used to determine the in vitro functions of RNF152. Mouse xenograft models were used to study the in vivo effects of RNF152. The immunoprecipitation assay was used to determine the interaction between RNF152 and TSPAN12. The in vivo ubiquitination assay was performed to determine the regulation of TSPAN12 by RNF152. RESULTS: We found that RNF152 is significantly down-regulated in clinic HCC samples, and its down-regulation is associated with pool overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) in HCC patients. The transcription factor FoxO1 was significantly positively correlated RNF152 expression in HCC tissues. FoxO1 recognizes a classic insulin response element (IRE) on the RNF152 promoter to regulate its expression in HCC. RNF152 suppressed HCC cell proliferation, clonogenic survival, invasion in vitro, and tumorigenesis in vivo. Mechanistically, RNF152 interacted with TSPAN12 and targeted it for ubiquitination and proteasomal degradation, thereby inhibiting TSPAN12-dependent CXCL6 expression and HCC progression. CONCLUSION: Collectively, our data revealed a tumor suppressor role of RNF152 and a connection between RNF152 and FoxO1 in HCC. Our results support an important role of the FoxO1-RNF152-TSPAN12 axis in the development of HCC. Therapeutic targeting this axis may be an effective means of treating HCC.

[Research progress of medial buttress plate assisted fixation for femoral neck fractures in young adults].

OBJECTIVE: To summarize the research progress of medial buttress plate assisted fixation for femoral neck fractures in young adults. METHODS: The literature about buttress plate assisted fixation for femoral neck fractures in young adults was widely reviewed and analyzed. The design principle, background, biomechanical characteristics, and clinical results of buttress plate were summarized. RESULTS: Medial buttress plate assisted fixation is the latest treatment of femoral neck fractures in young adults, which can convert the shear force at the fracture sides into compression force and promote fracture healing. Medial buttress plate can improve the biomechanical stability of femoral neck fractures and reduce the maximum stress of fixation implants. In clinical, the medial buttress plate can maintain fracture reduction, reduce the incidences of nonunion and surgical failure, and improve hip joint function. CONCLUSION: Medial buttress plate assisted fixation can achieve good effectiveness for femoral neck fractures in young adults. However, due to the preliminary application, its indications, fixation implants, and long-term effectiveness need to be further studied and improved.

Biomechanical analysis of minimally invasive crossing screw fixation for calcaneal fractures: Implications to early weight-bearing rehabilitation.

BACKGROUND: Minimally invasive fixation using crossing screws was believed to produce satisfactory clinical outcome whereas its stability in early weight-bearing remained controversial. This study aimed to analyze the biomechanical stability of minimally invasive fixation during balanced standing and walking stance, and provide evidence for early rehabilitation. METHODS: A finite element model of foot-ankle-shank complex was reconstructed based on computed tomography and magnetic resonance images, and validated by plantar pressure of the model participant. A Sanders III calcaneal fracture was created on the model, and then fixed using crossing screws. The predicted stress distribution, fracture displacement, Bohler's angle and Gissane's angle were compared between the intact calcaneus and fracture model with the fixation. FINDINGS: Postoperatively, the concentrated stress appeared at the junction of the calcaneus and its surrounding tissues (especially Achilles tendon, plantar fascia and ligaments) during standing and walking stances, and the stress exceeded the yield strength of trabecular bone. The longitudinal screws sustained the highest stresses and concentrated at the tips and the calcaneal tuberosity junction. The displacement of posterior joint facet, Bohler's angle, and Gissane's angle were within the acceptable range either standing or walking after the fixation. INTERPRETATION: Early weight-bearing standing and walking after minimally invasive fixation may cause high stress concentration thereby induce calcaneus stress fractures and other complications like plantar fasciitis and heel pain, so it should not be supported. The peri-calcaneus tendons, i.e., Achilles tendon and plantar fascia, play key roles in the stabilization of the calcaneal fracture after operation.

Clinical Characteristics and Eosinophils in Young SARS-CoV-2-Positive Chinese Travelers Returning to Shanghai.

Background: The COVID-19 outbreak, which was first reported in Wuhan, China, in December 2019, began to spread throughout the world, and now involves over 200 countries. Methods: A total of 37 overseas young and middle-aged people, who tested as SARS-CoV-2 positive upon their return to Shanghai, were enrolled for an analysis of their clinical symptoms, blood routine indexes, and lung CT images. Results: The clinical symptoms were characterized by fever (51.4%), dry cough (13.5%), expectoration (27.0%), hypodynamia (21.6%), pharyngalia (10.8%), pharynoxerosis (8.1%), rhinobyon (13.5%), rhinorrhea (8.1%), muscular soreness (16.2%), and diarrhea (2.7%). In 16.2% of cases, no symptoms were reported. Fever was the most common symptom (51.40%). The pneumonic changes referred to the latticed ground glass imaging and similar white lung imaging accompanied by consolidated shadows. The rate of pneumonia was high (81.10%). We found that the exclusive percent of eosinophils was abnormally low. By analyzing the correlation of eosinophils, fever, and pneumonia, we found that the percentage of eosinophils was low in the COVID-19 patients afflicted with fever or pneumonia (P < 0.01). Additionally, pneumonia and fever were negatively correlated with the percentage of eosinophils and eosinophils/neutrophils ratio (P < 0.01, respectively), but not associated with pneumonia severity (P > 0.05). Fever was not correlated with pneumonia (P > 0.05). Conclusion: A low percentage of eosinophils may be considered as a biomarker of pneumonia of COVID-19, but not as a biomarker of pneumonia severity.

Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice.

OBJECTIVE: Long-term glucocorticoids (GCs) therapy usually causes many metabolic side effects, including fatty liver. However, the molecular mechanisms remain poorly understood. Herein, we explored the molecular basis of GCs in the development of fatty liver. METHODS: C57BL/6 male mice were injected with Dexamethasone (DEX) while mouse primary hepatocytes (MPHs), HepG2 and Hep1-6 cells were cultured in the presence of DEX. Genes expression in liver tissues and hepatocytes were assessed by quantitative real-time PCR and western blotting, respectively. To explore whether Periostin is involved in the development of GCs-induced fatty liver, wild-type and Periostin knockout mice were treated with DEX or vehicle control. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the regulatory roles of GCs on Periostin expression. RESULTS: We show that treatment of dexamethasone (DEX), a synthetic analog of GCs, led to the accumulation of triglycerides in the livers of mice, but not in cultured hepatocytes, suggesting that GCs may promote liver steatosis through integrative organ crosstalk mediated by systemic factors. We further found that DEX upregulated the expression levels of Periostin in white adipose tissues, which in turn promoted liver steatosis. Administration of a Periostin-neutralizing antibody or genetic ablation of Periostin largely attenuated DEX-induced hepatic steatosis in mice. CONCLUSIONS: Our findings provided a novel insight that GCs could promote liver steatosis through integrative organ crosstalk mediated by white fat-secreted Periostin. These results establish Periostin as an endocrine factor with therapeutic potential for the treatment of GCs-associated fatty liver.

Computational modelling of foot orthosis for midfoot arthritis: a Taguchi approach for design optimization.

PURPOSE: Evaluation of the internal biomechanics of the foot-and-ankle complex is challenging for the prescription of orthosis particularly for midfoot arthritis patients in which the joint condition is crucial. METHODS: Using computational modeling and design optimization techniques, the objective of this study was to compare the biomechanical functions among different combinations of design factors using computer simulation. A finite element foot model was reconstructed from a midfoot arthritis patient. Orthotic designs with 3 levels for each of the 3 design factors (arch height, lateral wedge angle, and insole stiffness) contributed to 9 configurations using a fractional factorial design were tested. RESULTS: An increase in peak plantar stress of the midfoot was facilitated by a medium arch height and wedge angle, and stiffest insole material, notwithstanding the combination neither reduced the peak plantar stress of other foot regions nor was consistent with the combination that minimized the stress of the articular cartilage. CONCLUSIONS: Insole with high arch (H = 30 mm), low stiffness (E = 1.0 MPa), and medium wedge angle (A = 5°) could minimize the stress of the cartilage at the arthritic joint (primary outcome) and could be beneficial to the patients. Also, insole stiffness predominantly influenced cartilage stress. However, secondary outcomes including the stress of the navicular and medial cuneiform and the regional plantar stress did not produce the same solution. Future studies can consider a patient-specific loading profile to further the investigation on the stabilizing effect and the attenuation of load transfer induced by the insole.

Characterization and engineering control of the effects of reactive oxygen species on the conversion of sterols to steroid synthons in Mycobacterium neoaurum.

The conversion of sterols to steroid synthons by engineered mycobacteria comprises one of the basic ways for the production of steroid medications in the pharmaceutical industry. Here, we revealed that high amounts of reactive oxygen species (ROS) generate during the conversion process of sterols, which impairs the cell viability of mycobacterial cells and thus hinders the conversion of sterols to steroid synthons. Accordingly, the endogenous antioxidants for detoxifying ROS in mycobacteria, ROS scavenging enzymes and low molecular weight thiols, were examined. The results revealed that three antioxidants, catalase (CAT), mycothiol (MSH), and ergothioneine (EGT), demonstrated efficacy toward neutralizing the excessive ROS produced during sterol metabolism. CAT overexpression or MSH or EGT augmentation enhanced the conversion of phytosterols to 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) by 18.9%, 23.8%, and 32.1%, respectively, and also enhanced the cell viability, indicating the benefits of these antioxidants in reducing ROS-induced stress. Further combinatorial augmentation of CAT, MSH, and EGT demonstrated enhanced effects toward intracellular ROS scavenging, resulting in 54.2% greater cell viability and 47.5% enhancement in 4-HBC production. These findings indicated that the excessive ROS induces cell stress, in turn limiting the conversion of sterols, whereas neutralization of the excessive ROS by combined control of CAT, MSH, and EGT serves as an effective strategy to boost the conversion productivity of sterols to steroid synthons.

Enhanced conversion of sterols to steroid synthons by augmenting the peptidoglycan synthesis gene pbpB in Mycobacterium neoaurum.

Some species of mycobacteria have been modified to transform sterols to valuable steroid synthons. The unique cell wall of mycobacteria has been recognized as an important organelle to absorb sterols. Some cell wall inhibitors (e.g., vancomycin and glycine) have been validated to enhance sterol conversion by interfering with transpeptidation in peptidoglycan biosynthesis. Therefore, two transpeptidase genes, pbpA and pbpB, were selected to rationally modify the cell wall to simulate the enhancement effect of vancomycin and glycine on sterol conversion in a 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) producing strain (WIII). Unexpectedly, the pbpA or pbpB gene augmentation was conducive to the utilization of sterols. The pbpB augmentation strain WIII-pbpB was further investigated for its better performance. Compared to WIII, the morphology of WIII-pbpB was markedly changed from oval to spindle, indicating alterations of the cell wall. Biochemical analysis indicated that the altered cell wall properties of WIII-pbpB might contribute to the positive effect on sterol utilization. The productivity of 4-HBC was enhanced by 28% in the WIII-pbpB strain compared to that of WIII. These results demonstrated that the modification of peptidoglycan synthesis can improve the conversion of sterols to steroid synthons in mycobacteria.

A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation.

BACKGROUND: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation. METHODS: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined. RESULTS: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells. CONCLUSIONS: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.

Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury.

The spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via modulating mitophagy and apoptosis after spinal cord ischemia-reperfusion injury remains unclear. This study was undertaken to investigate the potential role of rapamycin in modulating mitophagy and mitochondria-dependent apoptosis using the spinal cord ischemia-reperfusion injury (SCIRI) mouse model. We found that rapamycin significantly (p < 0.05) enhanced mitophagy by increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. At the same time, rapamycin significantly (p < 0.05) decreased mitochondrial apoptosis related protein (Apaf-1, Caspase-3, Caspase-9) expression by inhibiting Bax translocation to the mitochondria and the release of the cytochrome c from the mitochondria. After 24 h following SCIRI, rapamycin treatment reduced the TUNEL+ cells in the spinal cord ischemic tissue and improved the locomotor function in these mice. Our results therefore demonstrate that rapamycin can improve the locomotor function by promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application in a spinal cord injury.