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In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.
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Traumatismos da Medula Espinal , Animais , Ratos , Traumatismos da Medula Espinal/tratamento farmacológico , Catecóis/farmacologia , Álcoois Graxos/farmacologiaRESUMO
BACKGROUND: Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD). METHODS: GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed. RESULTS: A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted. CONCLUSION: This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications.
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Degeneração do Disco Intervertebral , Disco Intervertebral , Humanos , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Fatores de Transcrição , Autofagia/genética , Metilprednisolona , Glucosamina/metabolismo , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Homeodomínio/metabolismoRESUMO
Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage.
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Exossomos , Traumatismos da Medula Espinal , Polpa Dentária , Exossomos/metabolismo , Humanos , Macrófagos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia , Células-TroncoRESUMO
Long noncoding RNA (lncRNA) has emerged as a pivotal regulator improving neural regeneration in the progression of spinal cord injury (SCI). However, whether lncRNAs can be targeted for therapeutic intervention of SCI remains unclear. In this study, we found that LINC00707 expression was significantly up-regulated in lipopolysaccharide (LPS)-treated PC-12, a model that mimics nerve cell injury in an inflammatory environment after SCI. Suppression of LINC00707 alleviated LPS-induced inflammation and apoptosis in PC-12 cells. Furthermore, we found that LINC00707 adsorbed miR-30a-5p and silenced miR-30a-5p or overexpressed Neurod 1 reversed the effect of LINC00707 on the inflammation and apoptosis of LPS-treated PC-12 cells. These findings revealed that LINC00707 alleviates LPS-induced inflammation and apoptosis in PC-12 cells by targeting miR-30a-5p/Neurod 1, providing a preliminary theoretical basis for the clinical application of LINC00707 in SCI.
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Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , RNA Longo não Codificante/antagonistas & inibidores , Animais , Apoptose/genética , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Células PC12 , Ratos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND: A study to evaluate the prevalence of uric acid (UA) nephrolithiasis with dual-energy CT (DECT) and explore the risk factors for kidney stones in primary gout patients. METHODS: Eighty-four consecutive gout patients underwent urinary tract ultrasonography or DECT to confirm the existence of kidney stones. Urine and blood samples were also taken for laboratory analysis. RESULTS: Forty-one subjects (48.8%) had nephrolithiasis diagnosed; 38 had a kidney stone. Thirty-two of the 38 patients underwent a DECT scan, and 27 patients had nephrolithiasis in DECT. Among them, 63.0% (17/27) and 14.8% (4/21) of the patients had pure UA and UA-based mixed stone, respectively, and 22.2% (6/27) had a non-UA stone. Those with nephrolithiasis suffered from more frequent acute attacks and had longer disease durations of gout. At least one urine biochemical abnormality was found in 81% of patients. Forty-four (55.0%) patients presented hypomagnesuria. Forty-three (51.8%) patients had low urine volume. Unduly acidic urine (UAU) was present in 36 patients (44.4%). Hyperuricosuria was only found in ten (12.2%) patients. In comparison to the non-lithiasic group, the lithiasic group was more likely to have a UAU. Binary logistic regression showed that female gender was a protective factor, while disease duration of gout and low urine pH were risk factors for nephrolithiasis. CONCLUSION: Our results indicated that nephrolithiasis, especially UA stones, were more common than previous reports in gout patients indicated, and that disease duration of gout, and low urine pH, were risk factors for nephrolithiasis.
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Cálculos Renais/química , Cálculos Renais/epidemiologia , Tomografia Computadorizada por Raios X , Ácido Úrico/análise , Adulto , Idoso , China , Feminino , Gota/complicações , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/etiologia , Masculino , Pessoa de Meia-Idade , Nefrolitíase/diagnóstico por imagem , Nefrolitíase/epidemiologia , Nefrolitíase/etiologia , Prevalência , Tomografia Computadorizada por Raios X/métodosRESUMO
In this paper, the binding properties of teicoplanin and vancomycin to bovine serum albumin (BSA) were investigated using fluorescence quenching, synchronous fluorescence, Fourier transform infrared (FTIR), circular dichroism (CD) and UV-vis spectroscopic techniques and molecular docking under simulative physiological conditions. The results obtained from fluorescence quenching data revealed that the drug-BSA interaction altered the conformational structure of BSA. Meanwhile, the 3D fluorescence, CD, FTIR and UV-vis data demonstrated that the conformation of BSA was slightly altered in the presence of teicoplanin and vancomycin, with different reduced α-helical contents. The binding distances for the drug-BSA system were provided by the efficiency of fluorescence resonance energy transfer (FRET). Furthermore, the thermodynamic analysis implied that hydrogen bond and van der Waals' forces were the main interaction for the drug-BSA systems, which agreed well with the results from the molecular modeling study. The results obtained herein will be of biological significance in future toxicological and pharmacological investigation.
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Soroalbumina Bovina/química , Teicoplanina/química , Vancomicina/química , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Modelos Moleculares , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
STUDY DESIGN: Systematic literature review. OBJECTIVES: To develop a predictive model for osteoporotic vertebral compression fractures (OVCF) in the elderly, utilizing current tools that are sensitive to bone and paraspinal muscle changes. METHODS: A retrospective analysis of data from 260 patients from October 2020 to December 2022, to form the Model population. This group was split into Training and Testing sets. The Training set aided in creating a nomogram through binary logistic regression. From January 2023 to January 2024, we prospectively collected data from 106 patients to constitute the Validation population. The model's performance was evaluated using concordance index (C-index), calibration curves, and decision curve analysis (DCA) for both internal and external validation. RESULTS: The study included 366 patients. The Training and Testing sets were used for nomogram construction and internal validation, while the prospectively collected data was for external validation. Binary logistic regression identified nine independent OVCF risk factors: age, bone mineral density (BMD), quantitative computed tomography (QCT), vertebral bone quality (VBQ), relative functional cross-sectional area of psoas muscles (rFCSAPS), gross and functional muscle fat infiltration of multifidus and psoas muscles (GMFIES+MF and FMFIES+MF), FMFIPS, and mean muscle ratio. The nomogram showed an area under the curve (AUC) of 0.91 for the C-index, with internal and external validation AUCs of 0.90 and 0.92. Calibration curves and DCA indicated a good model fit. CONCLUSIONS: This study identified nine factors as independent predictors of OVCF in the elderly. A nomogram including these factors was developed, proving effective for OVCF prediction.
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Central sarcopenia is associated with the prognosis of various orthopedic surgeries in the elderly. This study aims to investigate its impact on the outcomes of single-segment lumbar fusion surgery in elderly patients. Retrospective analysis was conducted on 314 patients aged 60 to 80 who underwent single-segment posterior lumbar fusion surgery due to degenerative lumbar diseases. Patients were categorized into high psoas and L4 vertebral index (PLVI) and low PLVI groups according to the MRI-measured PLVI for central sarcopenia. Basic patient data, surgery-related parameters, functional assessments at preoperative and postoperative 3, 6, and 12 months, and X-ray-based fusion status were compared. The basic data of the two groups showed no significant differences. Parameters including the operative segment, preoperative hemoglobin levels, surgical duration, and intraoperative blood loss exhibited no significant variances. However, notable differences were observed in postoperative initial hemoglobin levels, transfusion requirements, and length of hospital stay between the two groups. During the postoperative follow-ups at 3, 6, and 12 months, the VAS scores for lower back pain and ODI scores in the lower PLVI group were significantly higher compared to the high PLVI group. Additionally, the EuroQoL 5D scores were notably lower in the low PLVI group. There were no significant differences between the groups in terms of leg pain VAS scores at each time point and the fusion status at 12 months postoperatively. MRI-based central sarcopenia has a negative impact on the therapeutic effectiveness following single-segment lumbar fusion surgery in elderly patients.
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Sarcopenia , Fusão Vertebral , Idoso , Humanos , Estudos Retrospectivos , Sarcopenia/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Imageamento por Ressonância Magnética , Hemoglobinas , Fusão Vertebral/efeitos adversos , Resultado do TratamentoRESUMO
Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E.
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Antioxidantes , Tocotrienóis , Antioxidantes/química , Vitamina E , alfa-Tocoferol , TocoferóisRESUMO
Spinal cord injury (SCI) causes neuroinflammation, neuronal death, and severe axonal connections. Alleviating neuroinflammation, protecting residual cells and promoting neuronal regeneration via endogenous neural stem cells (eNSCs) represent potential strategies for SCI treatment. Extracellular vesicles (EVs) released by mesenchymal stem cells have emerged as pathological mediators and alternatives to cell-based therapies following SCI. In the present study, EVs isolated from untreated (control, C-EVs) and TGF-ß1-treated (T-EVs) mesenchymal stem cells were injected into SCI mice to compare the therapeutic effects and explore the underlying mechanisms. Our study demonstrated for the first time that the application of T-EVs markedly enhanced the proliferation and antiapoptotic ability of NSCs in vitro. The infusion of T-EVs into SCI mice increased the shift from the M1 to M2 polarization of reactive microglia, alleviated neuroinflammation, and enhanced the neuroprotection of residual cells during the acute phase. Moreover, T-EVs increased the number of eNSCs around the epicenter. Consequently, T-EVs further promoted neurite outgrowth, increased axonal regrowth and remyelination, and facilitated locomotor recovery in the chronic stage. Furthermore, the use of T-EVs in Rictor-/- SCI mice (conditional knockout of Rictor in NSCs) showed that T-EVs failed to increase the activation of eNSCs and improve neurogenesis sufficiently, which suggested that T-EVs might induce the activation of eNSCs by targeting the mTORC2/Rictor pathway. Taken together, our findings indicate the prominent role of T-EVs in the treatment of SCI, and the therapeutic efficacy of T-EVs for SCI treatment might be optimized by enhancing the activation of eNSCs via the mTORC2/Rictor signaling pathway.
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The wound healing process was often accompanied by bacterial infection and inflammation. The combination of electrically conductive nanomaterials and wound dressings could accelerate cell proliferation through endogenous electrical signaling, effectively promoting wound healing. In this study, polypyrrole was modified with dopamine hydrochloride by an in situ polymerization to form dopamine-polypyrrole (DA-Ppy) conductive nanofibers which successfully enhanced the water dispersibility and biocompatibility of polypyrrole. The DA-Ppy nanofibers were dispersed in an aqueous solution for >48â¯h and still maintained good stability. In addition, the DA-Ppy nanofibers showed good photothermal properties, and the temperature could reach 59.7⯰C by 1.5â¯W/cm2 near-infrared light irradiation (NIR) for 10â¯min. DA-Ppy conductive nanofibres could be well dispersed in 3,4-dihydroxyphenylpropionic acid modified chitosan-carboxymethylated ß-cyclodextrin modified gelatin (CG) hydrogel due to the presence of DA, which endowed CG/DA-Ppy hydrogel with good adhesion properties, and the hydrogel adhered to the pigskin would not be dislodged by washing with running water. Under NIR, the CG/DA-Ppy hydrogel showed significant antimicrobial properties. Moreover, the CG/DA-Ppy hydrogel had excellent biocompatibility. In addition, CG/DA-Ppy hydrogel was effective in scavenging ROS, inducing macrophage polarization towards the M2 phenotype, and modulating the level of wound inflammation in vitro. Finally, it was confirmed in rat-infected wounds that the tissue regeneration effect and collagen deposition in the CG/DA-Ppyâ¯+â¯NIR group were significantly better than the other groups in the repair of infected wounds, indicating better repair of infected wounds. The results suggested that the photothermal, antioxidant DA-Ppy conductive nanofiber had great potential for application in infected wound healing.
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Sports-related damage is a prevalent issue, which a combination therapy including photothermal irradiation, self-healing dressing and antibacterial treatment is an effective way to rehabilitate it. In the study, a multifunctional hydrogel was developed to meet the requirement. Firstly, mesoporous polydopamine (MPDA) was prepared, where gold nanoparticles (Au NPs) were formed in its mesoporous structure, to construct Au@MPDA NPs with nanosize about 200 nm. Synergetic and efficient photothermal effect was achieved by the combination of the two photothermal agents. The Au@MPDA NPs were then added to modify polyvinyl alcohol-carboxymethyl chitosan-borax (PCB) hydrogel. Via rheological property characterization, cell experiments and antibacterial evaluation, high photothermal efficiency and effective antibacterial activity of Au@MPDA@PCB hydrogel was obtained with the aid of Au@MPDA NPs, together with self-healing property. When treated in motion-related tissue, the modified hydrogel showed excellent adaptive property and photothermal effect in situ. This study is beneficial for developing a novel rehabilitation treatment strategy for sports-related injuries.
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Nanopartículas Metálicas , Nanopartículas , Prunella , Ouro/farmacologia , Hidrogéis , Antibacterianos/farmacologiaRESUMO
Purpose: The COVID-19 pandemic has adversely impacted the mental health of the population. The current study aimed to determine the prevalence of depressive symptoms and sleep disturbances among Chinese college students during the COVID-19 pandemic and investigate the correlations between chronotypes, sleep quality, and depressive symptoms. Participants and Methods: In the current study, 2526 college students responded anonymously to an online questionnaire survey from 26 May 2020 to 20 July 2020. The participants' chronotypes, sleep quality, and depressive symptoms were evaluated using the Chinese version of the Morning and Evening Questionnaire-5 (MEQ-5), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire-9 (PHQ-9). Sociodemographic information of the participants was also acquired. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) 19.0 software, with the mediating effect assessed by Hayes' PROCESS Macro. Results: During the COVID-19 pandemic, the prevalence of depressive symptoms and sleep disturbances among Chinese college students surveyed was 54.95% and 48.18%, respectively. From absolute evening chronotype to absolute morning chronotype, the surveyed college students' chronotypes were negatively correlated with their depressive symptoms. Moreover, the mediation analysis showed that the correlation between chronotypes and depressive symptoms was fully mediated by sleep quality. Eveningness college students with poorer sleep quality were more likely to report higher levels of depressive symptoms. Conclusion: Our findings suggest that during the COVID-19 pandemic, delayed circadian preference (ie, eveningness) may be linked to worse depressive symptoms among Chinese college students, and call for more attention to the sleep quality of Chinese college students as sleep quality fully mediated the correlation between chronotypes and depressive symptoms among them. Reasonable adjustment in bedtime/circadian preference and improvement in sleep quality may help to reduce the prevalence and severity of depressive symptoms among Chinese college students.
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BACKGROUND: Spinal infection with sparganosis is rarely seen, and multiple spinal infections with sparganosis in the thoracic spine have not been reported. CASE SUMMARY: In this case report, a 56-year old male patient suffered from back pain for 3 mo. Computed tomography examination of the thoracic spine showed bone destruction of the T4-5 vertebral body, as well as the right pedicle and lamina of T5. Magnetic resonance imaging showed high signals on T2W1 images and fat-suppressed images in the right vertebral body of T4-5 and the right pedicle and lamina of T5, a high signal in the vertebral canal, and similar high signals in the paravertebral and subcutaneous regions of the whole spine. Puncture biopsy showed sparganosis. Following definite diagnosis, the patient was treated with debridement of T4-5 infected lesions under a microscope, bone grafting and internal fixation. Postoperatively, the patient's back pain symptoms were significantly relieved; the incision healed after one-stage treatment, and albendazole antiparasitic treatment was administered. CONCLUSION: Puncture biopsy is the most reliable method to diagnose infection by sparganum. Removal of infected lesions under the microscope and albendazole for antiparasitic treatment are safe and effective.
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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual loss of midbrain dopaminergic neurons in association with aggregation of α-synuclein. Oxidative damage has been widely implicated in this disease, though the mechanisms involved remain elusive. Here, we demonstrated that preferential accumulation of peroxidized phospholipids and loss of the antioxidant enzyme glutathione peroxidase 4 (GPX4) were responsible for vulnerability of midbrain dopaminergic neurons and progressive motor dysfunctions in a mouse model of PD. We also established a mechanism wherein iron-induced dopamine oxidation modified GPX4, thereby rendering it amenable to degradation via the ubiquitin-proteasome pathway. In conclusion, this study unraveled what we believe to be a novel pathway for dopaminergic neuron degeneration during PD pathogenesis, driven by dopamine-induced loss of antioxidant GPX4 activity.
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Ferroptose , Doença de Parkinson , Camundongos , Animais , Dopamina/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Neurônios Dopaminérgicos/metabolismo , Antioxidantes , Ferroptose/genética , Doença de Parkinson/metabolismo , Mesencéfalo/metabolismo , alfa-Sinucleína/metabolismo , UbiquitinaçãoRESUMO
In this work, the interaction of chlortetracycline with bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking. Results indicated that chlortetracycline quenches BSA fluorescence mainly by a static quenching mechanism. The quenching constants (K(SV) ) were obtained as 5.64 × 10(4) , 4.49 × 10(4) , and 3.44 × 10(4/) M(-1) at 283, 295, and 307 K, respectively. The thermodynamic parameters of enthalpy change Δ H°, entropy change Δ S°, and free energy change Δ G° were -5.12 × 10(4/) J mol(-1), -97.6 J mol(-1) K(-1), and -2.24 × 10(4/) J mol(-1) (295 K), respectively. The association constant (K(A) ) and the number of binding sites (n) were 9.41 × 10(3) M(-1) and 0.86, respectively. The analysis results suggested that the interaction was spontaneous, and van der Waals force and hydrogen-bonding interactions played key roles in the reaction process. In addition, CD spectra proved secondary structure alteration of BSA in the presence of chlortetracycline.
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Antibacterianos/química , Clortetraciclina/química , Simulação de Acoplamento Molecular , Soroalbumina Bovina/química , Algoritmos , Animais , Sítios de Ligação , Bovinos , Dicroísmo Circular , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica , Estabilidade Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Espectrometria de Fluorescência , TermodinâmicaRESUMO
OBJECTIVE: This study was performed to examine the clinical outcomes of epidural and intradural decompression for degenerative cervical myelopathy. METHODS: The data for 13 patients who underwent epidural and intradural decompression for treatment of degenerative cervical myelopathy (study group) and 20 patients who underwent only cervical laminoplasty, fusion, and epidural decompression (historical control group) were retrospectively reviewed. The preoperative and postoperative neurological status was evaluated using the Japanese Orthopaedic Association (JOA) score. RESULTS: All patients' neurological symptoms were significantly improved at the final follow-up. In the study group, the patients' mean preoperative JOA score was 8.07 ± 1.80, and the final score improved by 70.88% ± 21.18%. The blood loss and operation time were significantly greater in the study group than control group. The recovery time was shorter in the study group than control group. The improvement rate was not significantly different between the two groups. CONCLUSIONS: A pia mater incision with separation of the arachnoid adhesion can significantly improve the cerebrospinal fluid flow and spinal blood flow in degenerative cervical myelopathy. Arachnoid adhesion can lead to intradural spinal scar compression. The surgical intervention described herein can achieve satisfactory neurological outcomes and shorten the recovery time.
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Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos , Laminoplastia , Doenças da Medula Espinal/cirurgia , Fusão Vertebral , Adulto , Idoso , Aracnoide-Máter/cirurgia , Terapia Combinada/métodos , Espaço Epidural/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pia-Máter/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the capacity and efficiency of human umbilical cord mesenchymal stem cells (HUCMSCs) to differentiate into neuron- like cells after induction with B27- supplemented serum- free medium. METHODS: HUCMSCs at passage 4 were cultured for 14 days with serum-containing medium (SCM) (group A), SCM supplemented with 20 ng/mL nerve growth factor (NGF) and 10 ng/mL basic fibroblast growth factor (bFGF) (group B), serum-free medium (SFM) (group C), or SFM supplemented with 20 ng/mL NGF and 10 ng/mL bFGF. The culture medium were changed every 3 days and the growth of the neurospheres was observed using an inverted microscope. The cell markers were analyzed with flow cytometry and the expressions of nestin, neuron- specific enolase (NSE), neurofilament heavy polypeptide (NEFH), and glial fibrillary acidic protein (GFAP) were quantified by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Before induction, HUCMSCs expressed abundant mesenchymal stem cell surface markers including CD29 (99.5%), CD44 (49.6%) and CD105 (77.7%). Neuron-like cells were observed in the cultures on days 7, 10, and 14, and the cell differentiation was the best in group D, followed by groups C, B and A. In all the 4 groups, the cellular expressions of nestin and GFAP gradually lowered while those of NEFH and NSE increased progressively. The expressions of GFAP, NEFH, nestin and NSE were significantly different between group A and the other 3 groups (P < 0.001 or 0.05). CONCLUSIONS: B27-supplemented SFM effectively induces the differentiation of HUCMSCs into neuron- like cells, and the supplementation with cytokines (NGF and bFGF) strongly promotes the cell differentiation.
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Células-Tronco Mesenquimais , Células Cultivadas , Suplementos Nutricionais , Humanos , Neurônios , Cordão UmbilicalRESUMO
Estrogen deficiency, which mainly occurs in postmenopausal women, is a primary reason for osteoporosis in clinical diagnosis. However, the molecular regulation of osteoporosis in menopausal females is still not adequately explained in the literature, with the diagnosis and treatment for osteoporosis being limited. Herein, exosomal microRNAs (miRNAs) were used to evaluate their diagnosis and prediction effects in menopausal females with osteoporosis. In this study, 6 menopausal females without osteoporosis and 12 menopausal females with osteoporosis were enrolled. The serum exosomes were isolated, and the miRNA expression was detected by miRNA high-throughput sequencing. Exosomal miRNA effects were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The miRNA-targeted genes were evaluated by Targetscan 7.2 and the protein-protein interactions (PPI) by STRING. Hub genes were analyzed by the CytoHubba app of Cytoscape. The results showed that 191 aberrant miRNAs were found in the group of menopausal females with osteoporosis, including 72 upregulated miRNAs and 121 downregulated miRNAs. Aberrant miRNAs were involved in many signaling pathways, such as the Wnt, MAPK, and Hippo pathways. Based on PPI network analysis, FBXL3, FBXL13, COPS2, UBE2D3, DCUN1D1, DCUN1D4, CUL3, FBXO22, ASB6, and COMMD2 were the 10 most notable genes in the PPI network. In conclusion, aberrant serum exosomal miRNAs were associated with an altered risk of osteoporosis in menopausal females and may act as potential biomarkers for the prediction of risk of osteoporosis in menopausal females.
Assuntos
Biomarcadores/sangue , Exossomos/genética , Perfilação da Expressão Gênica/métodos , Menopausa/genética , MicroRNAs/genética , Osteoporose/diagnóstico , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Menopausa/sangue , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/genética , Mapas de Interação de Proteínas , Análise de Sequência de RNARESUMO
OBJECTIVE: To investigate the compensatory mechanism of maintaining the sagittal balance in degenerative lumbar scoliosis patients with different pelvic incidence (PI). METHODS: This was a retrospective imaging observation study. Patients in our department with degenerative lumbar scoliosis between 2017 and 2019 were reviewed. A total of 36 patients were eligible and included in the present study. The average age of those patients was 64.22 years, including 8 men and 28 women. The coronal and sagittal parameters were measured on full-length spine X-ray film, including globe kyphosis (GK), lumber lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), sagittal vertical axis (SVA), sagittal shift angle, Cobb angle, coronal shift angle, and vertebra. The anterior pelvic plane angle (APPA) and pelvic parameters were also measured, including the pelvic tilt (PT), the PI, and the sacral slope (SS). PI-LL, LL-SS, and GK-SS were calculated. Traditional pelvic tilt was also calculated using the following formula: cPT = PI × 0.37-7. These patients were divided into two groups according to their PI values. The patients' PI value in Group 1 was smaller than 50°. The patients' PI value in Group 2 was equal to or larger than 50°. RESULTS: These patients' SS, PT, PI, LL, TLK, TK, and GK were 28.70° ± 11.36°, 23.28° ± 6.55°, 52.00° ± 11.03°, 31.66° ± 14.12°, 12.12° ± 14.9°, 17.81° ± 13.53°, and -13.17° ± 16.27°. The sagittal shift angle, the APPA, the Cobb angle, the coronal shift angle, vertebra, PI-LL, cPT, APPA-4, LL-SS, and GK-SS were 4.38° ± 5.75°, -12.55° ± 8.83°, 30.03° ± 12.59°, 2.40° ± 2.13°, 4.08 ± 0.93, 19.86° ± 10.97°, 12.35° ± 4.55°, -8.30° ± 9.07°, 3.30° ± 8.82°, and 15.53° ± 9.83°, respectively. There was no significant difference between PT and cPT + APPA-4 or between cPT and PT-APPA+4. There was significant difference between PT and cPT + APPA or between cPT and PT-APPA. This demonstrated that the APPA-4 is reliable as degree of the pelvic sagittal retroversion. There were significant differences in SS, PI, LL, TLK, GK, APPA, PT-APPA, PT-APPA+4, cPT, and APPA-4 between Group 1 and Group 2. There were no significant differences in PT, TK, sagittal shift angle, SVA, Cobb angle, coronal shift angle, vertebra number, PI-LL, cPT + APPA, cPT + APPA-4, LL-SS, and GK-SS between Group 1 and Group 2. The Pearson tests showed that PI-LL had significant correlations with TK, LL, sagittal shift angle, SVA, and LL-SS. There was no significant correlation between PI-LL and Cobb angle, GK, TLK, APPA, vertebra, Coronal Shift Angle, or GK-SS. CONCLUSION: The APPA-4 is reliable as degree of the pelvic sagittal retroversion. In degenerative lumbar scoliosis, patients with smaller PI tended to rely more on the pelvic retroversion to maintain the sagittal balance than patients with larger PI, or patients with smaller PI were likely to start up the pelvic retroversion compensatory mechanism earlier than the patients with larger PI.