RESUMEN
A neural network (NN)-based electrical dispersion pre-compensation (pre-EDC) scheme in intensity-modulation and direct-detection (IM/DD) systems is proposed and experimentally demonstrated in this Letter. The scheme enables 56â Gbit/s four-level pulse amplitude modulation (PAM-4) generation at a transmitter over an 80â km single-mode fiber (SMF) transmission in the C-band. The NN is utilized to better fit nonlinear phase-amplitude transformation due to the chromatic dispersion (CD) in IM/DD systems, in place of the existing Gerchberg-Saxton (GS) iterative algorithm and linear GS-based finite impulse response (GS-FIR) non-iterative compensation schemes. The experimental results show that the measured bit error ratio (BER) can be reduced to below the 7% hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 with 0â dBm receiver optical power (ROP) by the NN-based non-iterative pre-EDC scheme, which also saves up to 81% of computational complexity compared to the GS-based scheme. The results indicate that our proposed scheme is promising for the CD pre-compensation at the transmitter.
RESUMEN
BACKGROUND: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. METHODS: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. RESULTS: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50-26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15-28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25-35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. CONCLUSIONS: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.
Asunto(s)
Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/epidemiología , Humanos , Incidencia , Salud Global , Femenino , MasculinoRESUMEN
A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRß+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.
Asunto(s)
Matriz Extracelular , Hidrogeles , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Animales , Hidrogeles/química , Ratas , Matriz Extracelular/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Perros , Axones/metabolismo , Axones/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Ácido Hialurónico/química , Ácido Hialurónico/metabolismo , Recuperación de la Función/efectos de los fármacos , Dopamina/metabolismo , Femenino , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Médula Espinal/metabolismoRESUMEN
Objective: To explore the predictive value of the nerve root sedimentation sign in the diagnosis of lumbar spinal stenosis (LSS). Methods: Between January 2019 and July 2021, 201 patients with non-specific low back pain (NS-LBP) who met the selection criteria were retrospectively analyzed. There were 67 males and 134 females, with an age of 50-80 years (mean, 60.7 years). Four intervertebral spaces (L 1, 2, L 2, 3, L 3, 4, L 4, 5) of each case were studied, with a total of 804. The nerve root sedimentation sign was positive in 126 intervertebral spaces, and central canal stenosis was found in 203 intervertebral spaces. Progression to symptomatic LSS was determined by follow-up for lower extremity symptoms similar to LSS, combined with central spinal stenosis. Univariate analysis was performed for gender, age, visual analogue scale (VAS) score for low back pain at initial diagnosis, treatment, dural sac cross-sectional area at each intervertebral space, number of spinal stenosis segments, lumbar spinal stenosis grade, positive nerve root sedimentation sign, and number of positive segments between patients in the progression group and non-progression group, and logistic regression analysis was further performed to screen the risk factors for progression to symptomatic LSS in patients with NS-LBP. Results: All patients were followed up 17-48 months, with an average of 32 months. Of 201 patients with NS-LBP, 35 progressed to symptomatic LSS. Among them, 33 cases also had central spinal stenosis, which was defined as NS-LBP progressing to symptomatic LSS (33 cases in progression group, 168 cases in non-progression group). Univariate analysis showed that CSA at each intervertebral space, the number of spinal stenosis segments, lumbar spinal stenosis grade, whether the nerve root sedimentation sign was positive, and the number of nerve root sedimentation sign positive segments were the influencing factors for the progression to symptomatic LSS ( P<0.05); and further logistic regression analysis showed that positive nerve root sedimentation sign increased the risk of progression of NS-LBP to symptomatic LSS ( OR=8.774, P<0.001). Conclusion: The nerve root sedimentation sign may be associated with the progression of NS-LBP to symptomatic LSS, and it has certain predictive value for the diagnosis of LSS.
Asunto(s)
Dolor de la Región Lumbar , Vértebras Lumbares , Raíces Nerviosas Espinales , Estenosis Espinal , Humanos , Estenosis Espinal/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/etiología , Valor Predictivo de las Pruebas , Imagen por Resonancia MagnéticaRESUMEN
AIMS: Spinal cord injury (SCI) is a devastating neurological disease that often results in tremendous loss of motor function. Increasing evidence demonstrates that diabetes worsens outcomes for patients with SCI due to the higher levels of neuronal oxidative stress. Mammalian sterile 20-like kinase (MST1) is a key mediator of oxidative stress in the central nervous system; however, the mechanism of its action in SCI is still not clear. Here, we investigated the role of MST1 activation in induced neuronal oxidative stress in patients with both SCI and diabetes. METHODS: Diabetes was established in mice by diet induction combined with intraperitoneal injection of streptozotocin (STZ). SCI was performed at T10 level through weight dropping. Advanced glycation end products (AGEs) were applied to mimic diabetic conditions in PC12 cell line in vitro. We employed HE, Nissl staining, footprint assessment and Basso mouse scale to evaluate functional recovery after SCI. Moreover, immunoblotting, qPCR, immunofluorescence and protein-protein docking analysis were used to detect the mechanism. RESULTS: Regarding in vivo experiments, diabetes resulted in up-regulation of MST1, excessive neuronal apoptosis and weakened motor function in SCI mice. Furthermore, diabetes impeded NRF2-mediated antioxidant defense of neurons in the damaged spinal cord. Treatment with AAV-siMST1 could restore antioxidant properties of neurons to facilitate reactive oxygen species (ROS) clearance, which subsequently promoted neuronal survival to improve locomotor function recovery. In vitro model found that AGEs worsened mitochondrial dysfunction and increased cellular oxidative stress. While MST1 inhibition through the chemical inhibitor XMU-MP-1 or MST1-shRNA infection restored NRF2 nuclear accumulation and its transcription of downstream antioxidant enzymes, therefore preventing ROS generation. However, these antioxidant effects were reversed by NRF2 knockdown. Our in-depth studies showed that over-activation of MST1 in diabetes directly hindered the neuroprotective AKT1, and subsequently fostered NRF2 ubiquitination and degradation via the GSK3ß/ß-TrCP pathway. CONCLUSION: MST1 inhibition significantly restores neurological function in SCI mice with preexisting diabetes, which is largely attributed to the activation of antioxidant properties via the GSK3ß(Ser 9)/ß-TrCP/NRF2 pathway. MST1 may be a promising pharmacological target for the effective treatment of spinal cord injury patients with diabetes.
Asunto(s)
Apoptosis , Neuronas , Proteínas Serina-Treonina Quinasas , Traumatismos de la Médula Espinal , Animales , Ratones , Ratas , Antioxidantes/farmacología , Proteínas con Repetición de beta-Transducina/farmacología , Diabetes Mellitus , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Mamíferos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/metabolismo , Neuronas/metabolismo , Neuronas/patología , Diabetes Mellitus Experimental/metabolismoRESUMEN
OBJECTIVE: This study aimed to systematically evaluate the optimal surgical fusion approach for lumbar spondylolisthesis, to provide the latest and most reliable evidence for future clinical practice. METHODS: A comprehensive search of the PubMed, Ovid-Embase, Web of Science, Cochrane, and Scopus databases was conducted from inception to September 1, 2023, to identify relevant records. Two independent reviewers performed the literature screening, data extraction, and assessment of study quality. RESULTS: Fifteen randomized controlled trials involving 892 patients met the inclusion criteria. The network evidence plot showed that posterolateral fusion and posterior lumbar interbody fusion (PLIF) were the most used fusion techniques. The network meta-analysis results revealed that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) had a significantly greater improvement in the Oswestry Disability Index (ODI) compared to endoscopic-TLIF, while PLIF had a significantly better fusion effect than posterolateral fusion. Furthermore, no statistically significant differences were observed between other fusion surgeries in terms of improving ODI, fusion rate, complications, or the improvement of visual analog scale-low back pain. The surface under the cumulative ranking curve results indicated that MIS-TLIF had the greatest potential for improving ODI, visual analog scale-low back pain, and complications, while PLIF had the greatest potential for increasing fusion rates. However, the existing selection bias, measurement bias, reporting bias, and publication bias may have reduced the reliability of the meta-analysis results. CONCLUSIONS: Among the various fusion surgeries for lumbar spondylolisthesis, MIS-TLIF appears to provide the greatest benefit to patients. However, more high-quality, large-scale studies are needed to further investigate the treatment efficacy of different fusion surgeries for lumbar spondylolisthesis.
Asunto(s)
Vértebras Lumbares , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Fusión Vertebral , Espondilolistesis , Espondilolistesis/cirugía , Humanos , Fusión Vertebral/métodos , Vértebras Lumbares/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del TratamientoRESUMEN
STUDY DESIGN: A retrospective cohort study. PURPOSE: To analyze the association between preoperative adjacent facet joint osteoarthritis (FJOA) and outcomes of lumbar interbody fusion (LIF). OVERVIEW OF LITERATURE: Whether preoperative adjacent FJOA is associated with the incidence of radiological adjacent segment degeneration (RASD) and low back pain (LBP) relief after lumbar fusion remains unknown. METHODS: The study included patients who underwent LIF. The demographic characteristics and radiographic and surgical data were collected and evaluated. The included patients were divided into control group and FJOA group based on the preoperative adjacent facet joint Pathria grade. Preoperative and last follow-up LBP Visual Analog Scale (VAS) score, leg pain (LP) VAS, Oswestry Disability Index (ODI) and RASD were evaluated and compared. The improvement rates in VAS and ODI were calculated and compared between the two groups. Logistic regression was used to analyze the risk factors of LBP relief and incidence of RASD. RESULTS: In total, 197 patients (control group, 86; FJOA group, 111) were included, and the median follow-up was 46 months. The VAS and ODI in both groups significantly improved after surgery. At the last follow-up, the FJOA group had higher VAS and lower VAS improvement rates of LBP than the control group (p<0.05). However, no significant difference in the LP VAS and ODI was found between the two groups. The incidence of RASD in the FJOA group was significantly higher than that in the control group (48.6% vs. 30.2%, p=0.034). Multivariate logistic regression analysis showed that preoperative adjacent FJOA was significantly associated with LBP relief (odds ratio [OR], 0.691; 95% confidence interval [CI], 0.498-0.958) and the postoperative incidence of RASD (OR, 1.406; 95% CI, 1.020-1.939). CONCLUSIONS: The preoperative FJOA in the adjacent segments was significantly associated with LBP following LIF. Patients with preoperative FJOA were more likely to have RASD following lumbar fusion surgery.
RESUMEN
While Wallerian degeneration (WD) is a crucial pathological process induced with spinal cord injury (SCI), its underlying mechanisms is still understudied. In this study, we aim to assess structural alterations and clinical significance of WD in the cervical cord following SCI using multi-modal magnetic resonance imaging (MRI), which combines T2*-weighted imaging and diffusion tensor imaging (DTI). T2*-weighted images allow segmentation of anatomical structures and the detection of WD on macrostructural level. DTI, on the other hand, can identify the reduction in neuroaxonal integrity by measuring the diffusion of water molecules on the microstructural level. In this prospective study, 35 SCI patients (19 paraplegic and 16 tetraplegic patients) and 12 healthy controls were recruited between July 2020 and May 2022. The hyperintensity voxels in the dorsal column was manually labeled as WD on T2*-weighted images. The mean cross-sectional area (CSA) and mean DTI indexes of WD at the C2 level were calculated and compared between groups. Correlation analysis was used to determine the associations of the magnitude of WD with lesion characteristics and clinical outcomes. Compared with controls, SCI patients showed evident hyperintensity (35/35) and decreased neuroaxonal integrity (p < 0.05) within the dorsal column at the C2 level. A higher neurological level of injury was associated with a larger mean CSA and reduction in neuroaxonal integrity within WD (p < 0.05). Smaller total and dorsal tissue bridges were related to greater mean CSA and lower fractional anisotropy values in WD (p < 0.05), respectively. Moreover, SCI participants with significantly larger CSAs and significantly lower microstructural integrity had worse sensory outcomes (p < 0.05). This comprehensive evaluation of WD can help us better understand the mechanisms of WD, monitor progression, and assess the effectiveness of therapeutic interventions after SCI.
Asunto(s)
Médula Cervical , Traumatismos de la Médula Espinal , Degeneración Walleriana , Humanos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/patología , Masculino , Degeneración Walleriana/diagnóstico por imagen , Degeneración Walleriana/etiología , Degeneración Walleriana/patología , Femenino , Adulto , Persona de Mediana Edad , Médula Cervical/diagnóstico por imagen , Médula Cervical/lesiones , Médula Cervical/patología , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Adulto JovenRESUMEN
The nervous system is one of the most complicated and enigmatic systems within the animal kingdom. Recently, the emergence and development of spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) technologies have provided an unprecedented ability to systematically decipher the cellular heterogeneity and spatial locations of the nervous system from multiple unbiased aspects. However, efficiently integrating, presenting and analyzing massive multiomic data remains a huge challenge. Here, we manually collected and comprehensively analyzed high-quality scRNA-seq and ST data from the nervous system, covering 10 679 684 cells. In addition, multi-omic datasets from more than 900 species were included for extensive data mining from an evolutionary perspective. Furthermore, over 100 neurological diseases (e.g. Alzheimer's disease, Parkinson's disease, Down syndrome) were systematically analyzed for high-throughput screening of putative biomarkers. Differential expression patterns across developmental time points, cell types and ST spots were discerned and subsequently subjected to extensive interpretation. To provide researchers with efficient data exploration, we created a new database with interactive interfaces and integrated functions called the Spatiotemporal Cloud Atlas for Neural cells (SCAN), freely accessible at http://47.98.139.124:8799 or http://scanatlas.net. SCAN will benefit the neuroscience research community to better exploit the spatiotemporal atlas of the neural system and promote the development of diagnostic strategies for various neurological disorders.
Asunto(s)
Bases de Datos Genéticas , Enfermedades del Sistema Nervioso , Neuronas , Análisis de Expresión Génica de una Sola Célula , Animales , Neuronas/metabolismo , Atlas como Asunto , Enfermedades del Sistema Nervioso/genéticaRESUMEN
Unilateral biportal endoscopic (UBE) spine surgery is an emerging minimally invasive surgical (MIS) technique that has gained popularity for treating lumbar spinal stenosis, particularly in Eastern Asia. The traditional UBE technique, with two portals on one side, can achieve successful unilateral laminotomy for bilateral decompression (ULBD) and, therefore, demonstrates favorable clinical outcomes. However, in the case of lumbar spinal stenosis combined with contralateral disc herniation, it is very difficult to remove the contralateral disc herniation, especially the loose disc fragment within the deep disc. Here, a third channel of the traditional UBE technique was developed to do the discectomy within the ipsilateral endoscopic vision, with which the instruments can go vertically into the contralateral disc, allowing easy discectomy. This technique can not only achieve adequate decompression of the bilateral spinal canal but also effectively remove contralateral herniated disc fragments. This technique avoids performing another UBE procedure on the opposite side, which can potentially shorten the duration of the operation, minimize blood loss and tissue damage, and ensure sufficient neural decompression. This paper will introduce the indications and surgical operation procedures, as well as present a classical case report and follow-up data, to facilitate the application of the third channel-assisted UBE (T-UBE) technique for spine surgeons.
Asunto(s)
Desplazamiento del Disco Intervertebral , Estenosis Espinal , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Estenosis Espinal/cirugía , Vértebras Lumbares/cirugía , Resultado del Tratamiento , Endoscopía/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Spinal-pelvic sagittal balance is important for maintaining energy-efficient posture in normal and diseased states.Few reports to date have evaluated the effect of spinal-pelvic sagittal balance on clinical outcomes after lumbar interbody fusion in patients with lumbar degenerative diseases (LDD). METHODS: A total of 303 patients treated with posterior lumbar interbody fusion surgery for lumbar degenerative disease from January 2012 to December 2019 were enrolled in this retrospective study according to the inclusion criteria. Preoperative and postoperative spinal-pelvic sagittal parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL) of the patients were evaluated and compared. 163 patients whose postoperative PI-LL ≤ 10° were divided into the spinal-pelvic match group (Group M), while 140 patients were divided into the spinal-pelvic mismatch group (Group MM). Preoperative and postoperative Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) for back pain of both groups were compared. RESULTS: There was no significant difference between the two groups in demographic and surgical data, except for blood loss in surgery. LL, PI, PT and SS of the patients at final follow-up were all statistically different from the preoperative values in the two groups(P < 0.05). There was no significant difference in LL, PI, PT and SS between the two groups before surgery. At the final follow-up, LL, PI and PT differed significantly between the two groups(P < 0.05). Compared with the preoperative results, ODI and VAS of low back in both groups decreased significantly at the final follow-up (P < 0.05). Significant differences in VAS and ODI were found between the two groups at the final follow-up (P < 0.05). The improvement rates of VAS and ODI of Group M are both significantly higher than Group MM. Regression analysis showed that age and spinal-pelvic match had significant effects on the improvement of patients' low back pain at the final follow-up. CONCLUSIONS: lumbar interbody fusion can significantly improve the prognosis of patients with LDD. In terms of outcomes with an average follow-up time of more than 2 years, the spinal-pelvic match has a positive effect on patients' quality of life and the release of low back pain.
Asunto(s)
Lordosis , Dolor de la Región Lumbar , Fusión Vertebral , Animales , Humanos , Dolor de la Región Lumbar/cirugía , Dolor de la Región Lumbar/etiología , Estudios Retrospectivos , Calidad de Vida , Vértebras Lumbares/cirugía , Resultado del Tratamiento , Lordosis/cirugía , Fusión Vertebral/métodosRESUMEN
STUDY DESIGN: A retrospective case-series. OBJECTIVE: The study aims to use machine-learning (ML) to predict the discharge destination of spinal cord injury (SCI) patients in the intensive care unit (ICU). SUMMARY OF BACKGROUND DATA: Prognostication following SCI is vital, especially for critical patients who need intensive care. METHODS: Clinical data of patients diagnosed with SCI were extracted from a publicly available ICU database. The firstly recorded data of the included patients were used to develop a total of 98 ML classifiers, seeking to predict discharge destination (e.g. death, further medical care, home). The micro-average area under the curve (AUC) was the main indicator to assess discrimination. The best average-AUC classifier and the best death-sensitivity classifier were integrated into an ensemble classifier. The discrimination of the ensemble classifier was compared with top death-sensitivity classifiers and top average-AUC classifiers. Additionally, prediction consistency and clinical utility were also assessed. RESULTS: A total of 1485 SCI patients were included. The ensemble classifier had a micro-average AUC of 0.851, which was only slightly inferior to the best average-AUC classifier (P=0.10) The best average-AUC classifier death sensitivity was much lower than that of the ensemble classifier. The ensemble classifier had a death sensitivity of 0.452, which was inferior to top 8 death-sensitivity classifiers, whose micro-average AUC were inferior to the ensemble classifier (P<0.05). Additionally, the ensemble classifier demonstrated a comparable Brier score and superior Net benefit in the decision curve analysis, when compared to the performance of the origin classifiers. CONCLUSIONS: The ensemble classifier shows an overall superior performance in predicting discharge destination considering discrimination ability, prediction consistency and clinical utility. This classifier system may aid in the clinical management of critical SCI patients in the early phase following injury. LEVEL OF EVIDENCE: 3.
RESUMEN
OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease associated with excessive mechanical loading. The aim here was to elucidate whether different subpopulations of chondrocytes exhibit distinct phenotypes in response to variations in loading conditions. Furthermore, we seek to investigate the transcriptional switches and cell crosstalk among these chondrocytes subsets. METHODS: Proteomic analysis was performed on cartilage tissues isolated from weight-bearing and non-weight-bearing regions. Additionally, single-cell RNA sequencing was employed to identify different subsets of chondrocytes. For disease-specific cells, in vitro differentiation induction was performed, and their presence was confirmed in human cartilage tissue sections using immunofluorescence. The molecular mechanisms underlying transcriptional changes in these cells were analysed through whole-transcriptome sequencing. RESULTS: In the weight-bearing regions of OA cartilage tissue, a subpopulation of chondrocytes called OA hypertrophic chondrocytes (OAHCs) expressing the marker genes SLC39A14 and COL10A1 are present. These cells exhibit unique characteristics of active cellular interactions mediated by the TGFß signalling pathway and express OA phenotypes, distinct from hypertrophic chondrocytes in healthy cartilage. OAHCs are mainly distributed in the superficial region of damaged cartilage in human OA tissue, and on TGFß stimulation, exhibit activation of transcriptional expression of iron metabolism-related genes, along with enrichment of associated pathways. CONCLUSION: This study identified and validated the existence of a subset of OAHCs in the weight-bearing area of OA cartilage tissue. Our findings provide a theoretical basis for targeting OAHCs to slow down the progression of OA and facilitate the repair of cartilage injuries.
Asunto(s)
Cartílago Articular , Osteoartritis , Humanos , Condrocitos/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Proteómica , Cartílago Articular/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , FenotipoRESUMEN
Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.
Asunto(s)
Ferroptosis , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/metabolismo , Neuronas/metabolismo , Mitocondrias/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Hydrogel-based regenerated scaffolds show promise as a platform for neural regeneration following spinal cord injury (SCI). Nevertheless, the persistent problem of poor mechanical strength and limited integration with the host tissue still exists. In this study, a bioinspired hydrogel with highly sophisticated features for neural regeneration after SCI is developed. The hydrogel is composed of dihydroxyphenylalanine (DOPA)-grafted chitosan and a designer peptide, offering a unique set of qualities such as being injectable, having self-healing abilities, and adhering to tissues. Compared to conventional hydrogels, this hydrogel ensures a significant promotion of immune response modulation and axon regrowth while featuring synapse formation of various neurotransmitters and myelin regeneration. Subsequently, functional recoveries are enhanced, including motor function, sensory function, and particularly bladder defect repair. These positive findings demonstrate that the hydrogel has great potential as a strategy for repairing SCI. Moreover, the versatility of this strategy goes beyond neural regeneration and holds promise for tissue regeneration in other contexts. Overall, this proposed hydrogel represents an innovative and multifaceted tool for engineering structures in the biomedical field.
Asunto(s)
Hidrogeles , Traumatismos de la Médula Espinal , Humanos , Hidrogeles/química , Adhesivos/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Regeneración Nerviosa , PéptidosRESUMEN
Local reconstruction of a permissive environment with biomaterials is a promising strategy to treat spinal cord injury (SCI). We reported a hybrid hydrogel fabricated from a small functional self-assembling peptide (F-SAP) and large silk fibroin (SF). The diffusion of SF micelles into F-SAP solution was driven by the dynamic synergy between osmotic pressure and F-SAP/SF electrostatic interactions, resulting in the rearrangement of SF micelles and the formation of rod-like filaments with axes nearly perpendicular to F-SAP nanofibers. Spectroscopy analysis, including circular dichroism, Raman and fluorescence, indicated conformation changes of SF from random coil to ß sheet, which contributed to enhanced mechanical properties of the resultant hybrid hydrogel. Furthermore, the F-SAP/SF hybrid hydrogel coupled with controlled release of NT-3 provided a permissive environment for neural regeneration by providing nanofibrous substrates for regenerating axons, inflammatory modulation and remyelination, consequently resulting in improved locomotion and electrophysiological properties. This hydrogel could be used as a long-term stent in vivo for the treatment of SCI.
Asunto(s)
Fibroínas , Nanofibras , Traumatismos de la Médula Espinal , Humanos , Fibroínas/química , Nanofibras/química , Micelas , Péptidos/química , Hidrogeles/química , Traumatismos de la Médula Espinal/terapia , Andamios del Tejido/químicaRESUMEN
Triggering receptor expressed on myeloid cell 2 (TREM2) signaling often drives opposing effects in traumatic versus demyelinating CNS disorders. Here, we identify two distinct phenotypes of microglia and infiltrating myeloid populations dependent on TREM2 expression levels at the acute stage and elucidate how they mediate the opposing effects of TREM2 in spinal cord injury (SCI) versus multiple sclerosis animal models (experimental autoimmune encephalomyelitis [EAE]). High TREM2 levels sustain phagocytic microglia and infiltrating macrophages after SCI. In contrast, moderate TREM2 levels sustain immunomodulatory microglia and infiltrating monocytes in EAE. TREM2-ablated microglia (purine-sensing phenotype in SCI and reduced immunomodulatory phenotype in EAE) drive transient protection at the acute stage of both disorders, whereas reduced phagocytic macrophages and lysosome-activated monocytes lead to contrasting neuroprotective and demyelinating effects in SCI versus EAE, respectively. Our study provides comprehensive insights into the complex roles of TREM2 in myeloid populations across diverse CNS disorders, which has crucial implications in devising TREM2-targeting therapeutics.