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1.
Adv Sci (Weinh) ; 11(19): e2308850, 2024 May.
Article in English | MEDLINE | ID: mdl-38477452

ABSTRACT

A recently emerging cell death pathway, known as copper-induced cell death, has demonstrated significant potential for treating infections. Existing research suggests that cells utilizing aerobic respiration, as opposed to those reliant on glycolysis, exhibit greater sensitivity to copper-induced death. Herein, a MnO2-loaded copper metal-organic frameworks platform is developed denoted as MCM, to enhance bacterial cuproptosis-like death via the remodeling of bacterial respiratory metabolism. The reversal of hypoxic microenvironments induced a cascade of responses, encompassing the reactivation of suppressed immune responses and the promotion of osteogenesis and angiogenesis. Initially, MCM catalyzed O2 production, alleviating hypoxia within the biofilm and inducing a transition in bacterial respiration mode from glycolysis to aerobic respiration. Subsequently, the sensitized bacteria, characterized by enhanced tricarboxylic acid cycle activity, underwent cuproptosis-like death owing to increased copper concentrations and aggregated intracellular dihydrolipoamide S-acetyltransferase (DLAT). The disruption of hypoxia also stimulated suppressed dendritic cells and macrophages, thereby strengthening their antimicrobial activity through chemotaxis and phagocytosis. Moreover, the nutritional effects of copper elements, coupled with hypoxia alleviation, synergistically facilitated the regeneration of bones and blood vessels. Overall, reshaping the infection microenvironment to enhance cuproptosis-like cell death presents a promising avenue for eradicating biofilms.


Subject(s)
Biofilms , Copper , Biofilms/drug effects , Biofilms/growth & development , Animals , Copper/metabolism , Mice , Oxides/pharmacology , Manganese Compounds , Disease Models, Animal , Hypoxia/metabolism
2.
Biomed Pharmacother ; 172: 116225, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38306845

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes major motor, sensory and autonomic dysfunctions. Currently, there is a lack of effective treatment. In this study, we aimed to investigate the potential mechanisms of Exosomes from adipose-derived stem cells (ADSC-Exos) in reducing ferroptosis and promoting angiogenesis after spinal cord injury. METHODS: We isolated ADSC-Exos, the characteristics of which were confirmed. In vitro, we tested the potential of ADSC-Exos to promote the survival and function of human brain microvascular endothelial cells (HBMECs) and analyzed the ferroptosis of HBMECs. In vivo, we established rat models of SCI and locally injected ADSC-Exos to verify their efficacy. RESULTS: ADSC-Exos can reduce reactive oxygen species (ROS) accumulation and cell damage induced by an excessive inflammatory response in HBMECs. ADSC-Exos inhibit ferroptosis induced by excessive inflammation and upregulate the expression of glutathione peroxidase 4(GPX4) in HBMECs. It can also effectively promote proliferation, migration, and vessel-like structure formation. In vitro, ADSC-Exos improved behavioral function after SCI and increased the number and density of blood vessels around the damaged spinal cord. Moreover, we found that ADSC-Exos could increase nuclear factor erythroid-2-related factor 2(NRF2) expression and nuclear translocation, thereby affecting the expression of solute carrier family 7 member 11(SLC7A11) and GPX4, and the NRF2 inhibitor ML385 could reverse the above changes. CONCLUSION: Our results suggest that ADSC-Exos may inhibit ferroptosis and promote the recovery of vascular and neural functions after SCI through the NRF2/SLC7A11/GPX4 pathway. This may be a potential therapeutic mechanism for spinal cord injury.


Subject(s)
Ferroptosis , Spinal Cord Injuries , Humans , Animals , Rats , Endothelial Cells , NF-E2-Related Factor 2 , Recovery of Function , Amino Acid Transport System y+
3.
RSC Adv ; 14(1): 616-625, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38173607

ABSTRACT

In this paper, we use molecular dynamics to simulate the crack propagation behavior of gradient nano-grained (GNG) copper models with different grain size gradients, compare the crack propagation rates of different models, and analyze the microstructural changes and the mechanism of crack propagation. The simulation results show that the increase of the grain size gradient of the GNG copper model can improve the fracture resistance of the material, and the crack propagation mode undergoes a transition from brittle propagation along the grain boundaries to the formation of pores at the grain boundaries, and then to ductile fracture along the inclined plastic shear zone. The number of dislocations increases with the grain size gradient, while the crack passivation is more serious, indicating that a larger grain size gradient is more effective in inhibiting crack propagation. The introduction of gradient grain size promotes crack propagation and weakens the plasticity of the material relative to the nano-grained (NG) copper model.

4.
Eur Spine J ; 33(2): 453-462, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38252307

ABSTRACT

PURPOSE: Prospective comparison of the efficacy and safety of transforaminal endoscopic lumbar discectomy (TELD) with a 45° puncture angle versus traditional Thomas Hoogland endoscopy spine systems (THESYS) for the surgical treatment of L5/S1 lumbar disc herniation (LDH). METHODS: Consecutive patients with L5/S1 LDH who underwent TELD were randomized (1:1) assigned to the 45° TELD group and the THESYS group. Clinical outcomes were assessed at pre-operation, 1-day and 3/6-months post-operation till final follow-up. Surgical-related parameters, visual analogue scale (VAS) score, oswestry disability index (ODI), and modified MacNab criteria, and surgical complications were recorded and analysed. RESULTS: All patients were followed up for at least 24 months. Compared to the THESYS group, the 45° TELD group had a shorter operative time (P < 0.001) and intraoperative radiation time (P < 0.001) and a smaller VAS score for back pain (P < 0.001) and leg pain intraoperatively (P < 0.001). The VAS and ODI in the 45° TELD group were significantly better than those in the THESYS group within 3 months postoperatively. However, from 3 months on, both groups showed comparable VAS and ODI. There was no significant difference between the two groups of modified MacNab criteria. There were two cases of residual disc and two cases of recurrence that required reoperation in the THESYS group. CONCLUSION: For L5/S1 LDH, the 45° TELD technique was superior to traditional THESYS in terms of surgery-related parameters and faster improvement of VAS and ODI, with a lower complication rate.


Subject(s)
Foraminotomy , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Spinal Puncture , Lumbar Vertebrae/surgery , Endoscopy , Diskectomy
5.
Ann Transl Med ; 11(9): 314, 2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37405007

ABSTRACT

Background: Lumbar injuries are common among paratroopers during landing maneuvers. Although bracing is widely advocated to increase spine stability, the effect of lumbar bracing on parachuting has yet to be quantified and the Chinese parachutist does not have a uniform prophylactic brace. The aim is to compare the effects of a novel, self-designed and self-manufactured lumbosacral brace with two ordinary lumbar braces based on biomechanical assessment of the lumbar and lower extremity joints during parachute landing. Methods: The study cohort consisted of 30 elite male paratroopers. Each participant was instructed to jump off a platform at two different heights (60 and 120 cm, respectively) and land on the force plate in a half-squat posture. Participants at each height were tested under four different conditions (no brace, elastic brace, semi-rigid brace, and lumbosacral brace). The Vicon 3D motion capture system and force plate were used to record and calculate biomechanical data, such as vertical ground reaction forces (vGRFs), joint angles, moments, and energy absorption. After the experiment, every participant completed the study questionnaires. Results: The increase of the jumping height raised all the parameters significantly (P<0.01). The use of all three braces slightly decreased vGRF, and reduced the lumbar angle, moment, and angular velocity in the sagittal plane. The use of lumbosacral and semi-rigid braces restricted lumbar flexion more efficiently (P<0.05), and significantly increased the energy absorption of the hip joints (P<0.01) and hip flexion (P<0.01) at 120 cm. No significant effect of braces was found on the motion of knee and ankle joints. The subjective scores suggested that the lumbosacral brace was softer and more comfortable than the semi-rigid brace, and more effective than the elastic brace. Conclusions: The lumbosacral brace markedly restricted the lumbar motion in the sagittal plane than the elastic brace and was more comfortable than the semi-rigid brace. Therefore, the innovative design, high efficiency, and comfortable landing of the lumbosacral brace represent a reliable option for parachute jumping and training.

6.
Calcif Tissue Int ; 113(2): 207-215, 2023 08.
Article in English | MEDLINE | ID: mdl-37401976

ABSTRACT

Recent studies have discovered an association between the PFN1 gene and Paget's disease. However, it is currently unknown whether the PFN1 gene is related to osteoporosis. This study was performed to investigate the association of Single-Nucleotide Polymorphisms (SNPs) in the PFN1 gene with Bone Mineral Density (BMD) as well as bone turnover markers and osteoporotic fractures in Chinese subjects. A total of 2836 unrelated Chinese subjects comprising 1247 healthy subjects and 1589 osteoporotic fractures patients (Fracture group) were enrolled in this study. Seven tagSNPs (rs117337116, rs238243, rs6559, rs238242, rs78224458, rs4790714, and rs13204) of the PFN1 gene were genotyped. The BMD of the lumbar spine 1-4 (L1-4), femoral neck, and total hip as well as bone turnover markers, such as ß-C-Terminal telopeptide of type 1 collagen (ß-CTX) and Procollagen type 1 N-terminal Propeptide (P1NP), were measured. The association between 7 tagSNPs and BMD and bone turnover markers was analyzed in 1247 healthy subjects only. After age matching, we selected 1589 osteoporotic fracture patients (Fracture group) and 756 nonfracture controls (Control group, selected from 1247 healthy subjects) for a case-control study, respectively. For the case-control study, we used logistic regression to investigate the relationship between 7 tagSNPs and osteoporotic fractures risk. In the All group, the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.007). In the Female group, the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.005). In the Male group, the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the L1-4 (all P = 0.012); the rs13204, the rs78224458, and the PFN1 haplotype GAC were associated with the BMD of the femoral neck (all P = 0.012); the rs13204 and rs78224458 were associated with the BMD of the total hip (both P = 0.015); and the PFN1 haplotype GAT was associated with the ß-CTX (P = 0.013). In the subsequent case-control study, the rs13204 and rs78224458 in the male group were associated with the risk of L1-4 fracture (P = 0.016 and 0.010, respectively) and total hip fracture (P = 0.013 and 0.016, respectively). Our study reveals that PFN1 gene polymorphisms are associated with BMD in Chinese males and ß-CTX in Chinese people and confirmed the relationship between PFN1 gene polymorphisms and Chinese male osteoporotic fractures in a case-control study.


Subject(s)
Bone Density , Bone Remodeling , Osteoporotic Fractures , Female , Humans , Male , Biomarkers , Bone Density/genetics , Bone Remodeling/genetics , Case-Control Studies , East Asian People , Osteoporotic Fractures/genetics , Polymorphism, Single Nucleotide/genetics , Profilins/genetics
7.
8.
Clin Spine Surg ; 36(6): E252-E257, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36823701

ABSTRACT

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the mid-term results and technical possibilities of posterior endoscopic cervical decompression (PECD) in the treatment of cervical radiculopathy. SUMMARY OF BACKGROUND DATA: PECD has been used in the treatment of cervical radiculopathy for the past decades; there is a paucity of studies directly comparing its outcomes with anterior cervical discectomy and fusion (ACDF) for patients with single-level cervical radiculopathy. PATIENTS AND METHODS: From January 2016 to December 2018, clinical and radiologic data of 42 patients were collected. Patients were followed for a mean of 40.6 months (range: 30-54 mo) after surgery. Changes in cervical lordosis and degeneration of adjacent segments were analyzed. Dysphagia was assessed using the Bazaz score, and clinical outcomes were analyzed using the Neck Disability Index and visual analog scoring system. RESULTS: There were no significant differences in neurological outcomes between the two groups. Significant between-group differences in postoperative dysphagia were observed ( P < 0.05). There were significant differences in postoperative segmental Cobb angles and disc height between the two groups ( P < 0.05). Degenerative changes in the adjacent segments occurred in 5 patients in the ACDF group and 1 patient in the PECD group ( P < 0.05); no revision surgery was needed. CONCLUSIONS: Clinical outcomes of PECD for patients with unilateral radiculopathy were satisfactory. On the premise of a strict selection of indications, we consider this technique to be a safe supplement and alternative to ACDF for patients with unilateral cervical radiculopathy. Longer follow-up periods are required to confirm these observations.


Subject(s)
Deglutition Disorders , Diskectomy , Radiculopathy , Humans , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Decompression , Diskectomy/methods , Radiculopathy/diagnostic imaging , Radiculopathy/surgery , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome
9.
Multimed Tools Appl ; 82(2): 2941-2982, 2023.
Article in English | MEDLINE | ID: mdl-35469150

ABSTRACT

To manage the rumors in social media to reduce the harm of rumors in society. Many studies used methods of deep learning to detect rumors in open networks. To comprehensively sort out the research status of rumor detection from multiple perspectives, this paper analyzes the highly focused work from three perspectives: Feature Selection, Model Structure, and Research Methods. From the perspective of feature selection, we divide methods into content feature, social feature, and propagation structure feature of the rumors. Then, this work divides deep learning models of rumor detection into CNN, RNN, GNN, Transformer based on the model structure, which is convenient for comparison. Besides, this work summarizes 30 works into 7 rumor detection methods such as propagation trees, adversarial learning, cross-domain methods, multi-task learning, unsupervised and semi-supervised methods, based knowledge graph, and other methods for the first time. And compare the advantages of different methods to detect rumors. In addition, this review enumerate datasets available and discusses the potential issues and future work to help researchers advance the development of field.

10.
Pain Physician ; 25(8): E1191-E1198, 2022 11.
Article in English | MEDLINE | ID: mdl-36375189

ABSTRACT

BACKGROUND: Local anesthesia is feasible for both transforaminal and interlaminar approaches in percutaneous endoscopic lumbar discectomy (PELD). However, the optimal approach for PELD has not yet been established at the L5/S1 segment under local anesthesia with 1% lidocaine. OBJECTIVES: In this study, we compared the transforaminal approach with the interlaminar approach of PELD under local anesthesia for L5/S1 disc herniation (DH). STUDY DESIGN: This was a prospective randomized clinical trial. METHODS: From January 2019 to March 2020, 91 consecutive patients with L5/S1 DH who planned to undergo PELD in our unit were randomized to the transforaminal endoscopic lumbar discectomy (TELD, n = 46) or interlaminar endoscopic lumbar discectomy (IELD, n = 45). Both procedures were performed under local anesthesia with 1% lidocaine. The clinical outcomes were assessed as the Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI) score, and modified MacNab criteria. Patient satisfaction surveys and surgical complications were also recorded and analyzed. RESULTS: Compared to the IELD group, the TELD group had a shorter operative time and postoperative bed rest time (P < 0.001) but a longer radiation time (P < 0.001) and lower VAS scores for intraoperative back pain (P < 0.001) and leg pain (P < 0.001). At the postoperative follow-up, there were no significant differences between the 2 groups in the VAS scores, ODI scores, or modified MacNab criteria. The surveys showed a significantly higher satisfaction rate in the TELD group than in the IELD group (P = 0.014). Six patients in the IELD group (13.3%) needed extra intravenous injections of sufentanil because of intense pain during the procedure. In the IELD group, there were 2 cases of neuropathic pain after surgery. LIMITATIONS: Due to the study was included in a single spine center with a relatively small population and its relatively short-term follow-up, the study is not generalizable. CONCLUSIONS: Both TELD and IELD can provide good clinical outcomes for L5/S1 DH under local anesthesia with 1% lidocaine. TELD was superior to IELD in terms of surgical-related experience and complications.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Diskectomy, Percutaneous/methods , Lumbar Vertebrae/surgery , Intervertebral Disc Displacement/surgery , Anesthesia, Local , Prospective Studies , Retrospective Studies , Diskectomy , Endoscopy/methods , Pain/surgery , Lidocaine/therapeutic use , Treatment Outcome
11.
Heliyon ; 8(10): e11115, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36325134

ABSTRACT

Background: Transforaminal endoscopic lumbar discectomy (TELD) has been widely used for lumbar disc herniation. However, in some challenging cases such as very highly migrated disc herniation (VHMDH), traditional TELD is difficult to access the pathology. Methods: From January 2016 to December 2019, 63 patients with single-level VHMDH underwent TELD using targeted puncture and foraminotomy techniques were included. All patients were followed up for 26.5 months on average (range, 24-48 months). Operative time, length of hospital stay, visual analog scale (VAS) score, Oswestry Disability Index (ODI), modified MacNab criteria and surgical complications were evaluated. Results: The operative time was 40-120 min (56.8 on average). The length of hospitalization was 2.5 days (range, 2-4 d). VAS score decreased significantly from 5.5 ± 1.3 preoperatively to 1.9 ± 1.30 (p < 0.001) 1 day postoperatively, and to 0.9 ± 0.8 (p < 0.001) at the final follow-up. ODI score improved significantly from 23.5 ± 3.2 preoperatively to 13.4 ± 3.0 (p < 0.001) 1 day postoperatively; and 3.1 ± 1.2 (p < 0.001) at the final follow-up. According to the modified MacNab criteria, 40 patients (63.5%) showed excellent results, 20 patients (31.7%) were rated as good, 2 patients (3.2%) were rated as fine, and 1 patient (1.6%) was rated as bad at the final follow-up. No residual fragments, nerve root or cauda equina injury was shown in this series. One recurrent case was resolved by open surgery. Conclusions: With modified targeted puncture and foraminotomy techniques, VHMDH can be accessed safely and effectively, and satisfactory clinical outcomes can be obtained for these patients.

12.
Front Cell Infect Microbiol ; 12: 967584, 2022.
Article in English | MEDLINE | ID: mdl-36389162

ABSTRACT

Spinal infection is a rarely occurred pathology, whose diagnosis remains a major challenge due to the low sensitivity of culturing techniques. Metagenomic next-generation sequencing (mNGS) is a novel approach to identify the pathogenic organisms in infectious diseases. In this study, mNGS technology was adopted for pathogenic detection in spinal infection from the tissue and pus samples. Additionally, the diagnostic performance of mNGS for spinal infection was evaluated, by comparing it with that of the conventional microbial culture, with the histopathological results as the gold standard. Overall, 56 samples from 38 patients were enrolled for mNGS testing, and 69 samples were included for microbial culture. 30 patients (78.95%) were identified to be positive by the mNGS method, which was higher than that of microbial culture (17, 44.74%). The sensitivity and specificity of mNGS with pus samples were 84.2% and 100.0%, respectively, which outperformed those of microbial culture (42.1% and 100.0%). The pathogen identification results were applied to medication guidance, and all 38 patients experienced favorable outcomes at three months, followed-up post-treatment, without any adverse effects. These findings proved that mNGS was superior to microbial culture in pathogenic identification of the spinal infection, thereby showing great promise in guiding drug administration and improving clinical outcomes.


Subject(s)
Metagenome , Metagenomics , Humans , Metagenomics/methods , High-Throughput Nucleotide Sequencing/methods , Sensitivity and Specificity , Suppuration
13.
World Neurosurg ; 164: e1179-e1189, 2022 08.
Article in English | MEDLINE | ID: mdl-35660670

ABSTRACT

OBJECTIVE: In this study, we aimed to analyze the clinical outcomes of percutaneous transforaminal endoscopic debridement and drainage (PTEDD) with accurate pathogen detection for patients with infectious spondylitis of the thoracolumbar and lumbar spines. METHODS: From January 2017 to February 2019, a consecutive series of 43 patients with infectious spondylitis of the thoracolumbar and lumbar spine were surgically treated with PTEDD. Organism culture, next-generation DNA sequencing, and pathological examination of the sample extracted from the infectious site were performed for accurate microbiological diagnosis. All patients were followed up for 24-36 months. Clinical and radiological outcomes were analyzed preoperatively and postoperatively. RESULTS: Surgeries were completed successfully on all 43 patients under local infiltration anesthesia. Positive culture of the responsible organism was obtained in 33 cases (76.7%). Among the 43 patients who underwent next-generation DNA sequencing, 42 (97.7%) had positive results. Corresponding antibiotic medication was given based on the pathogen detection. The modified Macnab criteria were found to be excellent in 32 patients (74.4%) and good in 11 (25.6%). Postoperative magnetic resonance imaging showed that the abscess and infectious area were reduced significantly at 3 months and had disappeared or almost disappeared at the final follow-up. Spontaneous fusion was obtained in 30 patients (69.8%). No patients required revision or conversion to open debridement and reconstruction. CONCLUSIONS: For patients with infectious spondylitis of the thoracolumbar and lumbar spine, PTEDD is an effective and safe treatment. Next-generation DNA sequencing is a much more sensitive method for detecting the responsible organisms.


Subject(s)
Spondylitis , Debridement/methods , Drainage/methods , Humans , Lumbar Vertebrae/surgery , Retrospective Studies , Spondylitis/diagnostic imaging , Spondylitis/surgery , Treatment Outcome
14.
Mol Neurobiol ; 59(7): 4304-4314, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35505051

ABSTRACT

Since microglia-associated neuroinflammation plays a critical role in the progression of acute spinal cord injury, modulation of microglial activation has been suggested as a potential therapeutic strategy. Progranulin has been reported to exert neuroprotective effects by attenuating neuroinflammation, but whether these effects are due to the modulation of microglial polarization and the underlying mechanism remain unclear. Here, we investigated the effect of progranulin on microglial polarization and analyzed the crosstalk between microglial autophagy and polarization. We found that progranulin could reduce proinflammatory cytokine production at the lesion site and promote locomotor functional recovery after acute spinal cord injury. In vitro, we found that progranulin could activate microglia to acquire an anti-inflammatory phenotype and express IL-10. Moreover, progranulin-mediated enhancement of anti-inflammatory microglial polarization was attributed to the protection of lysosomal function and the enhancement of autophagic flux. Above all, progranulin exerts anti-inflammatory effects by protecting lysosomal function to enhance microglial autophagy, induce M2 microglial polarization, and ultimately improve neurological function after acute spinal cord injury. These results suggest that targeting the autophagy-lysosomal pathway to modulate microglial polarization and reduce neuroinflammation is a potential treatment for spinal cord injury.


Subject(s)
Microglia , Spinal Cord Injuries , Animals , Anti-Inflammatory Agents/pharmacology , Autophagy , Microglia/metabolism , Progranulins/metabolism , Rats , Spinal Cord/pathology , Spinal Cord Injuries/pathology
15.
J Oncol ; 2022: 3037348, 2022.
Article in English | MEDLINE | ID: mdl-35466322

ABSTRACT

Osteosarcoma (OS) is an aggressive malignant neoplasm that commonly occurs in adults and adolescents. The objectives of this work were to verify the role of microRNA- (miR-) 135a in OS and determine whether it can regulate the growth and cellular migration of OS by targeting mothers against decapentaplegic homolog 2 (SMAD2). miR-135a and SMAD2 mRNA expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR). Proliferation and migration of cells were studied using the Cell Counting Kit-8, EdU staining, and transwell invasion experiment. Additionally, a dual-luciferase reporter experiment was used to investigate the possible relationship between miR-135a and SMAD2's 3'-UTR. Immunohistochemistry was utilized to examine the expressions of SMAD2 and Ki67 in mouse tumor tissues to determine the influence of miR-135a on cancer progression in vivo. miR-135a was shown to be elevated in OS tissue samples as well as five cell lines. High expression levels of miR-135a were correlated with poor prognosis of OS patients. Cellular proliferation and migration were promoted by the upregulation of miR-135a with miR mimics; however, this effect was inhibited by SMAD2 overexpression. miR-135a was also shown to directly target the 3'-UTR of SMAD2. Animal experiments also demonstrated that miR-135a downregulation had an inhibitory effect on tumor growth in vivo. High expression levels of miR-135a promoted transplanted tumor development in vivo and the proliferation and migration of OS cells by targeting SMAD2. In summary, miR-135a may be a prospective therapeutic target for OS in the future.

16.
J Mater Chem B ; 10(11): 1805-1820, 2022 03 16.
Article in English | MEDLINE | ID: mdl-35199816

ABSTRACT

Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, and are characterized by drug resistance, toxin impairment and immunosuppression. Recently, reactive oxygen species (ROS)- and hyperthermia-based antimicrobial therapies have been developed to effectively destroy biofilms. However, almost all of them have failed to simultaneously focus on the immunosuppressive biofilm microenvironment and bacterial toxin-induced tissue damage. Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapy through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodot (EM@MoS2) nanoplatform. In the biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and are detained, thus staying away from their targets and mitigating tissue damage. Under near-infrared (NIR) laser irradiation, MoS2 nanodots, with superb photothermal and peroxidase (POD)-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possessed the ability to reverse the immunosuppressive microenvironment by skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevent infection relapse. Systematic in vitro and in vivo evaluations have demonstrated that EM@MoS2 achieves a remarkable antibiofilm effect. The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.


Subject(s)
Erythrocyte Membrane , Molybdenum , Nanotubes , Biofilms , Disulfides , Molybdenum/pharmacology , Reactive Oxygen Species
17.
Biomed Res Int ; 2021: 3376496, 2021.
Article in English | MEDLINE | ID: mdl-34337004

ABSTRACT

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.


Subject(s)
Cell Polarity , Culture Media, Conditioned/pharmacology , Lacticaseibacillus rhamnosus/chemistry , Macrophages/pathology , Microglia/pathology , Recovery of Function , Spinal Cord Injuries/physiopathology , Animals , Cell Polarity/drug effects , Cell Survival/drug effects , Female , Inflammation/pathology , Macrophages/drug effects , Microglia/drug effects , Motor Activity/drug effects , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/metabolism , Phosphorylation/drug effects , Rats , Recovery of Function/drug effects , Signal Transduction/drug effects
18.
Stem Cell Reports ; 12(2): 290-304, 2019 02 12.
Article in English | MEDLINE | ID: mdl-30713039

ABSTRACT

The adult CNS has poor ability to replace degenerated neurons following injury or disease. Recently, direct reprogramming of astrocytes into induced neurons has been proposed as an innovative strategy toward CNS repair. As a cell population that shows high diversity on physiological properties and functions depending on their spatiotemporal distribution, however, whether the astrocyte heterogeneity affect neuronal reprogramming is not clear. Here, we show that astrocytes derived from cortex, cerebellum, and spinal cord exhibit biological heterogeneity and possess distinct susceptibility to transcription factor-induced neuronal reprogramming. The heterogeneous expression level of NOTCH1 signaling in the different CNS regions-derived astrocytes is shown to be responsible for the neuronal reprogramming diversity. Taken together, our findings demonstrate that region-restricted astrocytes reveal different intrinsic limitation of the response to neuronal reprogramming.


Subject(s)
Astrocytes/physiology , Cellular Reprogramming/physiology , Neurons/physiology , Animals , Astrocytes/metabolism , Cells, Cultured , Central Nervous System/metabolism , Central Nervous System/physiology , Mice , Mice, Inbred C57BL , Neurons/metabolism , Receptor, Notch1/metabolism , Signal Transduction/physiology , Spinal Cord/metabolism , Spinal Cord/physiology
19.
J Sci Food Agric ; 99(6): 2835-2845, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30447081

ABSTRACT

BACKGROUND: In order to develop active packaging of lily products, we for the first time investigated the effects of phenyllactic acid (PLA) incorporated into a sodium alginate (SA)-based coating on the quality of minimally processed lily bulbs stored at 4 °C for 15 days. RESULTS: L9 (34 ) orthogonal array design showed that the optimal concentrations of PLA, SA and glycerinum were 0.03, 0.03 and 0.05 mol L-1 , respectively, to prepare a blend coating. It was noticed that a PLA-SA blend coating treatment could inhibit browning and maintain the firmness and ascorbic acid of minimally processed lily bulbs. Compared with the control, polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities of PLA-SA blend coating treated minimally processed lily bulbs reduced by about 31%, 21% and 29% on the 15th day, respectively. Total phenolic and quinone contents decreased, respectively, by 16% and 55% at the same time. Moreover, PLA-SA blend coating treatment eliminated the accumulation of malonaldehyde (MDA) while inhibiting microbial growth of minimally processed lily bulbs. CONCLUSIONS: These results showed PLA-SA blend coating could effectively maintain quality of minimally processed lily bulbs stored at 4 °C, and it might be a prospective technology. © 2018 Society of Chemical Industry.


Subject(s)
Alginates/chemistry , Lactates/chemistry , Lilium/chemistry , Plant Roots/chemistry , Food Preservation/methods
20.
Biomed Res Int ; 2017: 4079849, 2017.
Article in English | MEDLINE | ID: mdl-28875150

ABSTRACT

OBJECTIVE: To explore the safety and efficacy of transpseudarthrosis osteotomy with interbody fusion in the treatment of Ankylosing Spondylitis (AS) patients with kyphotic spinal pseudarthrosis by a single posterior approach. METHODS: Twelve consecutive patients with spinal pseudarthrosis underwent transpseudarthrosis osteotomy and interbody fusion with a polyetheretherketone (PEEK) cage by a single posterior approach. The operative time, intraoperative blood loss, and complications were recorded. Radiographic and clinical results were assessed preoperatively and at the final follow-up. RESULTS: The average operative time was 201.9 min and the mean blood loss was 817.5 ml. The visual analogue scale (VAS) improved significantly from 6.7 preoperatively to 1.1 at the final follow-up. The average correction of the segmental kyphosis at the level of the pseudarthrosis was 22.3°. Bony fusion was achieved in all patients, and there was no obvious loss of correction at follow-up. CONCLUSION: Transpseudarthrosis osteotomy at the level of the pseudarthrosis can be safely performed and surgical repair of pseudarthrosis with interbody fusion by a single posterior approach was feasible.


Subject(s)
Kyphosis/surgery , Osteotomy/methods , Pseudarthrosis/surgery , Spondylitis, Ankylosing/surgery , Adult , Female , Humans , Kyphosis/diagnostic imaging , Kyphosis/physiopathology , Male , Middle Aged , Pain Measurement/methods , Pseudarthrosis/diagnostic imaging , Pseudarthrosis/physiopathology , Spinal Fusion/methods , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/physiopathology , Treatment Outcome
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