Attenuating intervertebral disc degeneration through spermidine-delivery nanoplatform based on polydopamine for persistent regulation of oxidative stress.

As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.

METTL3 promotes microglial inflammation via MEF2C in spinal cord injury.

Spinal cord injury (SCI) is a significant contributor to disability in contemporary society, resulting in substantial psychological and economic burdens for patients and their family. Microglia-mediated inflammation is an important factor affecting the nerve repair of SCI patients. N6-methyladenosine (m6A) is a prevalent epigenetic modification in mammals, which shows a strong association with inflammation. However, the mechanism of m6A modification regulating microglia-mediated inflammation is still unclear. Here, we observed that METTL3, a m6A methylase, was increased in SCI mice and lipopolysaccharide (LPS)-exposed BV2 cells. Knockdown of METTL3 inhibited the increased expression of iNOS and IL-1ß induced by LPS in vitro. Subsequently, MEF2C, myocyte-specific enhancer factor 2C, was decreased in SCI mice and LPS-exposed BV2 cells. Knockdown of MEF2C promoted the expression of iNOS and IL-1ß. Sequence analysis showed that there were multiple highly confident m6A modification sites on the MEF2C mRNA. METTL3 antibody could pull down a higher level of MEF2C mRNA than the IgG in RNA binding protein immunoprecipitation assay. Knockdown of METTL3 promoted MEF2C protein expression and MEF2C mRNA expression, accompanied by a reduced m6A modification level on the MEF2C mRNA. Knockdown of MEF2C inhibited the anti-inflammatory effect of METTL3 siRNA. Our results suggest that METTL3 promotes microglia inflammation via regulating MEF2C mRNA m6A modification induced by SCI and LPS treatment.

Ginsenoside Rg1 promotes astrocyte-to-neuron transdifferentiation in rat and its possible mechanism.

INTRODUCTION: Neuronal loss caused by spinal cord injury (SCI) usually contributes to irreversible motor dysfunction. Promoting neuronal regeneration and functional recovery is vital to the repair of SCI. AIMS: Astrocytes, activated by SCI with high proliferative capacity and proximity to neuronal lineage, are considered ideal cells for neuronal regeneration. As previous studies identified several small molecules for the induction of astrocyte-to-neuron, we confirmed that ginsenoside Rg1, a neuroprotective herb, could promote the direct transdifferentiation of astrocyte-to-neuron in rat. METHODS AND RESULTS: Immunofluorescence staining showed that 26.0 ± 1.5% of the induced cells exhibited less astroglial properties and more neuronal markers with typical neuronal morphologies, reflecting 20.6 ± 0.9% of cholinergic neurons and 22.3 ± 1.9% of dopaminergic neurons. Western blot and qRT-PCR revealed that the induced cells had better antiapoptotic ability and Rg1-promoted neuronal transdifferentiation of reactive astrocytes might take effect through suppressing Notch/Stat3 signal pathway. In vivo, a revised SCI model treated by Rg1 was confirmed with faster functional recovery and less injury lesion cavity. CONCLUSION: In summary, our study provided a novel strategy of direct transdifferentiation of endogenous rat reactive astrocytes into neurons with Rg1 and promotion of neuronal regeneration after SCI.

Sweat contamination induced surgical site infections after spine surgery: Three case reports and literature review.

INTRODUCTION AND IMPORTANCE: Surgical site infection (SSI) is one of the most intractable complications following spine surgery during the early postoperative stage. Elderly (age > 70 years), body mass index > 30, smoking, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, anemia, low serum albumin, operation time > 3 h, and perioperative blood loss > 500 mL are the common risk factors of SSI after spine surgery. However, there are few published reports about sweat contamination induced surgical site infections with Staphylococcus epidermidis up to date. Staphylococcus epidermidis is a permanent member of the normal human microbiota and has emerged as an important opportunistic pathogen in SSI. We aim to detect the influence of sweat infiltration on SSI with Staphylococcus epidermidis and effective management. CASE PRESENTATION: A 73-year-old male, a 54-year-old male and a 73-year-old female were admitted to our hospital. All of them underwent posterior compression and fusion surgery with internal fixation and got surgical site infection after primary surgery. Two of them suffered moderate surgical site infection while the third patient with comorbidities suffered severe surgical site infection. Antibiotic therapy and debridement with internal fixation retained were utilized during which microbiological culture were taken. The moderate infection patients got fully recovered after debridement and primary suture while the serious one had recurrence after the first debridement, and then the second operation was performed. SSI, however, relapsed after three days. Vacuum-assisted closure (VAC) system was placed in the third debridement. The severe patient got well recovered and discharged after displacement of VAC system. CLINICAL DISCUSSION: This report serves to explore a normal but overlooked factor for SSI. SSI is one of the most intractable complications after spine surgery and the report introduce some uncomplicated but effective methods to moderate and severe SSI. CONCLUSION: Sweat-contaminated is an inducement of SSI with Staphylococcus epidermidis that should attract surgeons' attention. For mild infection, changing dressing and infrared treatment can achieve good results. For moderate infection, one debridement and primary suture are enough. For severe infection, early application of VAC system can reduce the number of debridement and achieve good clinical outcome.