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To investigate the efficacy of Frankincense-Myrrh in lumbar Intervertebral degenerative diseases (LIDD). The active components of frankincense-myrrh was retrieved with a unique system pharmacology platform for Traditional Chinese Medicine Systems Pharmacology (TCMSP). The LIDD-related target genes were screened with DisGeNET and Genecards databases. Then, STRING & Cytoscape were used for analyzing the Protein-Protein Interaction network. DAVID was used for analyzing Gene Ontology (GO) & Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, molecules of AutoDockVina and Pymol were used for docking the molecules for verifying active ingredients and key targets' binding force. The 105 LIDD-related targets identified in Ruxiang (RX)-Moyao (MY) involve 53 active ingredients. In addition, topological analysis was conducted for identifying the 12 key targets. According to the analysis results of GO & KEGG, RX-MY is significant for treating LIDD through participating in many pathways and biological processes, such as signaling pathways of inflammatory response reactive process, MAP kinase activity, TNF, and MAPK, etc. According to the dock results, the active components oxo-tirucalic, acid, isofouquierone, (7S, 8R, 9S, 10R, 13S, 14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta [a] phenanthrene-3,16-dion in RX-MY binds actively. The basic pharmacological action and RX-MY-related mechanism in the treatment of LIDD was revealed in this study for the first time. It is predicted that the results may provide a treatment plan for RX-MY with replacement of NSAIDs and warrant investigation of new therapeutic alternatives for LIDD. However, these predictions should be validated by relevant pharmacological trials.
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Degeneração do Disco Intervertebral , Simulação de Acoplamento Molecular , Farmacologia em Rede , Degeneração do Disco Intervertebral/tratamento farmacológico , Humanos , Farmacologia em Rede/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Vértebras LombaresRESUMO
PURPOSE: To compare the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion. METHODS: This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023484937). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of cortical bone trajectory (CBT) screw and pedicle screw (PS) internal fixation in the treatment of adjacent segment degeneration (ASD) after lumbar fusion from database establishment to November 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, Oswestry disability index (ODI), Visual analogue scale (VAS), disc height (DH), hospital length stay and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library. RESULTS: A total of 6 cohort studies (CS) and 1 randomized controlled study with a total of 420 patients were included in this study, including 188 patients in the CBT group and 232 patients in the PS group. The CBT group had lower intraoperative blood loss than the PS group [mean difference (MD) = -129.38, 95% CI (-177.22, -81.55), P < 0.00001] and operation time was shorter than that of the PS group [MD = -1.42, 95% CI (-2.63, -0.20), P = 0.02]. Early postoperative back and leg pain improved more significantly in the CBT group [MD = -0.77, 95% CI (-1.35, -0.19), P = 0.01; MD = -0.24, 95% CI (-0.37, -0.10), P = 0.0005]. CONCLUSION: Compared with PS, CBT for adjacent segment degeneration after lumbar fusion has the advantages of less intraoperative blood loss, shorter operation time, and less back and leg pain in the early postoperative period.
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Osso Cortical , Vértebras Lombares , Parafusos Pediculares , Fusão Vertebral , Humanos , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Osso Cortical/cirurgia , Vértebras Lombares/cirurgia , Resultado do Tratamento , Degeneração do Disco Intervertebral/cirurgia , Parafusos Ósseos , Duração da Cirurgia , Masculino , Feminino , Perda Sanguínea CirúrgicaRESUMO
In articular cartilage defect, particularly in arthroscopy, regenerative hydrogels are urgently needed. It should be able to firmly adhere to the cartilage tissue and maintain sufficient mechanical strength to withstand approximately 10 kPa of arthroscopic hydraulic flushing. In this study, we report a carbene-mediated ultra adhesive hybrid hydrogel paints for arthroscopic cartilage repair, which combined the photo initiation of double crosslinking system with the addition of diatomite, as a further reinforcing agent and biological inorganic substances. The double network consisting of ultraviolet initiated polymerization of hyaluronic acid methacrylate (HAMA) and carbene insertion chemistry of diazirine-grafted gelatin (GelDA) formed an ultra-strong adhesive hydrogel paint (H2G5DE). Diatomite helped the H2G5DE hydrogel paint firmly adhere to the cartilage defect, withstanding nearly 100 kPa of hydraulic pressure, almost 10 times that in clinical arthroscopy. Furthermore, the H2G5DE hydrogel supported cell growth, proliferation, and migration, thus successfully repairing cartilage defects. Overall, this study demonstrates a proof-of-concept of ultra-adhesive polysaccharide hydrogel paints, which can firmly adhere to the articular cartilage defects, can resist continuous hydraulic pressure, can promote effective cartilage regeneration, and is very suitable for minimally invasive arthroscopy.
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Artroscopia , Cartilagem Articular , Gelatina , Ácido Hialurônico , Hidrogéis , Metano , Gelatina/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Cartilagem Articular/efeitos dos fármacos , Animais , Metano/química , Metano/análogos & derivados , Metano/farmacologia , Proliferação de Células/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Adesivos/químicaRESUMO
BACKGROUND: Sciatica is a phrase used to describe radiating leg discomfort. The most common cause is lumbar disc herniation (LDH), which is considered to start in the nucleus pulposus. Advancements in lipidomics and metabolomics have unveiled the complex role of fatty acid metabolism (FAM) in both healthy and pathological states. However, the specific roles of fatty acid metabolism-related genes (FAMGs) in shaping therapeutic approaches, especially in LDH, remain largely unexplored and are a subject of ongoing research. METHODS: The junction of the weighted correlation network analysis (WGCNA) test with 6 FAMGs enabled the finding of FAMGs. Gene set variation analysis (GSVA) was used to identify the possible biological activities and pathways of FAMGs. LASSO was used to determine diagnostic effectiveness of the four FAMGs in diagnosing LDH. GSE124272, GSE147383, GSE150408, and GSE153761 were utilized to confirm the levels of expression of four FAMGs. RESULTS: Four FAMGs were discovered [Acyl-CoA Thioesterase 4 (ACOT4), Cytochrome P450 Family 4 Subfamily A Member 11 (CYP4A11), Acyl-CoA Dehydrogenase Long Chain (ACADL), Enoyl-CoA Hydratase and 3-Hydroxyacyl CoA Dehydrogenase (EHHADH)] For biological function analysis, mhc class ib receptor activity, response to thyroxine, response to l phenylalanine derivative were emphasized. CONCLUSIONS: FAMGs can help with prognosis and immunology, and provide evidence for fatty acid metabolism-related targeted therapeutics. In LDH, FAMGs and their interactions with immune cells might be therapeutic targets.
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Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.
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Glucocorticoides , Piroptose , Glucocorticoides/farmacologia , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Microglia/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Estresse Oxidativo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
STUDY DESIGN: Systematic review. OBJECTIVE: To compare the efficacy of the posterior approach and combined anterior-posterior approach in the treatment of ankylosing spondylitis (AS) with cervical spine fracture by meta-analysis. METHODS: The databases PubMed, Web of Science, Embase, and Cochrane Library were searched for studies on the comparison of the posterior approach group and the combined anterior-posterior approach group in the treatment of ankylosing spondylitis combined with cervical spine fracture from database establishment to August 2023. The procedure time, intraoperative blood loss, the rates of neurological improvement, mean change in the postoperative neurological function, complication rates, rates of revised surgery, and mortality were extracted. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library. RESULTS: A total of 11 retrospective cohort studies with a total of 215 patients were included in this study. The posterior approach group had lower intraoperative blood loss than the combined anterior-posterior approach group [Mean difference (MD) = -146.05, 95%CI(-187.40,-104.69), P < .00001]; the operation time was significantly less in the posterior approach group than in the combined anterior-posterior approach group [MD = -95.34, 95%CI(-113.13,-77.55), P < .00001]. There were no statistically significant differences in the neurological improvement rates, mean changes in postoperative neurological function, complication rates, modified surgery rates, and mortality rates. CONCLUSION: Both the posterior approach and combined anterior and posterior approach can achieve good results. Clinicians should develop an individualized approach based on the patient's fracture type, degree of spinal cord injury, fracture stability, fracture dislocation, general condition, and underlying disease.
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OBJECTIVE: To compare the efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in lumbar degenerative diseases. METHODS: This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023432460). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of unilateral BE-TLIF and MIS-TLIF in lumbar degenerative diseases from database establishment to May 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, postoperative drainage, Oswestry disability index, Visual analogue scale, lumbar lordosis, disk height, hospital length stay, fusion rate, and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library. RESULTS: A total of 14 cohort studies with a total of 1007 patients were included in this study, including 472 patients in the BE-TLIF group and 535 patients in the MIS-TLIF group. The BE-TLIF group had lower intraoperative blood loss than the MIS-TLIF group [mean difference (MD) = - 78.72, 95% CI (- 98.47, - 58.97), P < 0.00001] and significantly reduced postoperative drainage than the MIS-TLIF group [MD = - 43.20, 95% CI (- 56.57, - 29.83), P < 0.00001], and the operation time was longer than that of the MIS-TLIF group [MD = 22.68, 95% CI (12.03, 33.33), P < 0.0001]. Hospital length stay in BE-TLIF group was significantly less than that in MIS-TLIF group [MD = - 1.20, 95% CI (- 1.82, - 0.57), P = 0.0002]. CONCLUSION: Compared with MIS-TLIF, BE-TLIF for lumbar degenerative diseases has the advantages of less intraoperative blood loss, less early postoperative low back and leg pain, shorter postoperative hospital length stay, and faster early functional recovery.
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Vértebras Lombares , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Perda Sanguínea Cirúrgica , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Background: Since the poor response to existing anti-tuberculosis drugs and low drug concentration in local bone tissues, the traditional drug therapy does not result in satisfactory treatment of osteoarticular tuberculosis. Thus, we report a rifapentine release system with imparted bone targeting potential using tetracycline (TC) -modified nanoparticles (NPs). Methods: TC was conjugated to PLGA-PEG copolymer via a DCC/NHS technique. Rifapentine-loaded NPs were prepared by premix membrane emulsification technique. The resulting NPs were characterized in terms of physicochemical characterization, hemolytic study, cytotoxicity, bone mineral binding ability, in vitro drug release, stability test and antitubercular activity. The pharmacokinetic and biodistribution studies were also performed in mice. Results: Rifapentine loaded TC-PLGA-PEG NPs were proved to be 48.8 nm in size with encapsulation efficiency and drug loading of 83.3% ± 5.5% and 8.1% ± 0.4%, respectively. The release of rifapentine from NPs could be maintained for more than 60 h. Most (68.0%) TC-PLGA-PEG NPs could bind to HAp powder in vitro. The cellular studies revealed that NPs were safe for intravenous administration. In vivo evaluations also revealed that the drug concentration of bone tissue in TC-PLGA-PEG group was significantly higher than that in other groups at all time (p < 0.05). Both NPs could improve pharmacokinetic parameters without evident organ toxicity. The minimal inhibitory concentration of NPs was 0.094 µg/mL, whereas this of free rifapentine was 0.25 µg/mL. Conclusion: Rifapentine loaded TC-PLGA-PEG NPs could increase the amount of rifapentine in bone tissue, prolong drug release in systemic circulation, enhance anti-tuberculosis activity, and thereby reducing dose and frequency of drug therapy for osteoarticular tuberculosis.
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Hydatid bone disease is a zoonotic parasitic infection that is caused primarily by the tapeworm Echinococcus granulosus, and it continues to be a major public health concern in pastoral regions. The reconstruction of limb function after limb salvage surgery remains a challenge for clinicians. The purpose of this study was to determine the clinical efficacy of palliative treatment of the management of advanced pelvic hydatid bone disease. From March 2005 to December 2018, medical records and images of patients with advanced pelvic hydatid bone disease treated with surgery combined with antiparasitic chemotherapy were evaluated retrospectively. The Enneking classification was applied to determine the location of the lesion, and the Musculoskeletal Tumor Society score system was used for outcome evaluation. Fifteen patients who met the criteria were included in this study, with a mean follow-up of 4.40 ± 1.76 years. All patients received treatment with surgery combined with antiparasitic chemotherapy. The mean number of surgical interventions per patient for pelvic cystic echinococcosis was 5.3 (range, 2-9 interventions per patient). Recurrence of pelvic hydatid bone disease occurred in 5 patients and was managed successfully through repeated debridement procedures. Palliative treatment with limb salvage surgery was an effective and practical approach to the management of advanced pelvic hydatid bone disease. Standard antiparasitic chemotherapy, which included albendazole at a dose of 10 mg/kg/day administered in two daily doses for 3 to 6 months, was also considered an essential part of the overall treatment strategy.
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Doenças Ósseas , Equinococose , Animais , Humanos , Estudos Retrospectivos , Cuidados Paliativos , Equinococose/tratamento farmacológico , Equinococose/cirurgia , Albendazol/uso terapêutico , Antiparasitários/uso terapêutico , Zoonoses/tratamento farmacológico , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/cirurgiaRESUMO
BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).
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Coinfecção , Fraturas Expostas , Staphylococcus aureus Resistente à Meticilina , Osteomielite , Humanos , Estudos Retrospectivos , Escherichia coli , Coinfecção/tratamento farmacológico , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , China/epidemiologia , Osteomielite/epidemiologia , Osteomielite/etiologia , Osteomielite/tratamento farmacológicoRESUMO
OBJECTIVE: The goal in this study was to compare the efficacy and safety outcomes of vertebral column decancellation (VCD) and pedicle subtraction osteotomy (PSO) for patients with ankylosing spondylitis (AS) with thoracolumbar kyphotic deformity. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO). The authors conducted a computer search of PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Wei Pu Database to collect controlled clinical studies on the efficacy and safety of VCD and PSO for patients with AS with thoracolumbar kyphotic deformity. The search covered the period from database establishment to March 2023. Two researchers screened the literature, extracted data, and evaluated the risk of bias of the included studies; these researchers recorded the authors and the sample size, and they extracted data on the intraoperative blood loss, Oswestry Disability Index, spine sagittal parameters, operation time, and complications in each study. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library. RESULTS: A total of 6 cohort studies with a total of 342 patients were included in this study, including 172 patients in the VCD group and 170 patients in the PSO group. The VCD group had lower intraoperative blood loss than the PSO group (mean difference [MD] -274.92, 95% CI -506.63 to -43.20, p = 0.02); significant correction of the sagittal vertical axis compared with the PSO group (MD 7.32, 95% CI -1.24 to 15.87, p = 0.03), and the operation time was shorter than that of the PSO group (MD -80.28, 95% CI -150.07 to -10.48, p = 0.02). CONCLUSIONS: This systematic review and meta-analysis showed that VCD had more advantages than PSO in correcting the sagittal imbalance in the treatment of AS with thoracolumbar kyphotic deformity, and VCD had less intraoperative blood loss, shorter operation time, and satisfactory results in improving the quality of life.
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Cifose , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/cirurgia , Perda Sanguínea Cirúrgica , Qualidade de Vida , Vértebras Lombares/cirurgia , Resultado do Tratamento , Osteotomia/métodos , Cifose/diagnóstico por imagem , Cifose/cirurgia , Cifose/complicaçõesRESUMO
OBJECTIVE: To evaluate the efficacy and safety of tranexamic acid (TXA) in hemostasis in patients undergoing posterior lumbar interbody fusion (PLIF) by meta-analysis. METHODS: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022354812). The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trial (RCT) papers on the use of TXA in patients with PLIF from database establishment to August 2022. Two researchers screened the literature, extracted data, evaluated the risk of bias of the included studies, recorded the authors, sample size, type of study design, and TXA dose of each study, and extracted the intraoperative blood loss, number of blood transfusions, total blood loss, drainage volume, operation time, and incidence of deep venous thrombosis in each study. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library. RESULTS: A total of 14 RCTs with a total of 1681 patients were included in this study, including 836 patients in the TXA group and 845 patients in the control group. The intraoperative blood loss [mean difference (MD) = - 125.97, 95% confidence interval (CI) (- 138.56, - 113.37), P < 0.0001] and less total blood loss [MD = - 204.28, 95% CI (- 227.38, - 181.18), P < 0.00001] in TXA group were lower than the control group. Statistical significance was also observed in postoperative drainage volume [MD = - 115.03, 95% CI (- 123.89, - 106.17), P < 0.00001], operation time [MD = - 8.10, 95% CI (- 14.49, - 1.71), P = 0.01], and blood transfusion rate [odds ratio (OR) = 0.30, 95% CI (0.23, 0.39), P < 0.00001]. However, there was no statistical difference observed in the incidence of deep venous thrombosis [OR = 0.83, 95% CI (0.56, 1.21), P = 0.33]. CONCLUSION: The application of TXA in PLIF can reduce intraoperative blood loss, total blood loss, drainage volume, the incidence of transfusion events, and operation time without increasing the risk of deep venous thrombosis.
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Antifibrinolíticos , Ácido Tranexâmico , Trombose Venosa , Humanos , Ácido Tranexâmico/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Antifibrinolíticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Trombose Venosa/etiologiaRESUMO
Objectives: This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks. Materials and methods: Six-week-old female MRL/lpr mice (n=10) were considered young lupus model mice, and 18-week-old MRL/lpr mice (n=10) were considered old lupus model mice. Additionally, six-week-old (n=10) and 39-week-old (n=10) female Balb/c mice were used as the young and old controls, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of MT-CO1 in nine organs/tissues were detected via quantitative polymerase chain reaction (qPCR) and Western blot. Malondialdehyde (MDA) levels were determined with thiobarbituric acid colorimetry. The correlation coefficient of MT-CO1 mRNA levels and MDA levels in each organ/tissue at different ages was analyzed by Pearson correlation analysis. Results: The results showed that most non-immune organs/tissues (heart, lung, liver, kidneys, and intestines) showed increased MT-CO1 expression levels in younger MRL/lpr mice (p<0.05) and decreased MT-CO1 expression in older mice (p<0.05). Expression of MT-CO1 in the lymph nodes was low in younger mice but high in older mice. In other immune organs (spleen and thymus), MT-CO1 expression was low in older MRL/lpr mice. Lower mRNA expression and higher MDA levels were observed in the brains of MRL/lpr mice. However, all MRL/lpr mice showed higher MDA levels than Balb/c mice in every organ no matter younger or older MRL/lpr mice. Conclusion: Our study results suggest that lymphoid mitochondrial hyperfunction at organ level may be an important intrinsic pathogenesis in systemic lupus erythematosus activity, which may affect mitochondrial dysfunction in non-immune organs.
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Osteosarcoma (OS) is a kind of fatal primary bone tumors in adolescents and young adults. Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs which occupy a part of the latest hot topics. We aimed to investigate the roles of lncRNA LINC00665 in OS in this study. In this study, we found that LINC00665 was highly expressed in OS tissues and cell lines, and its high expression was associated with malignant feature and poor prognosis of OS. In OS cells, LINC00665 could facilitate the proliferation, migration, and invasion to play an oncogenic role. Mechanistically, LINC00665 served as a sponge for miR-708 and miR-142-5p and positively mediated the expression of their target RAP1B. Finally, we confirmed that LINC00665 exercised its biological functions by mediating RAP1B. In conclusion, LINC00665 is overexpressed in OS and facilitates the malignant processes of OS cells by increasing the RAP1B expression via sponging miR-708 and miR-142-5p.
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Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Adolescente , Apoptose/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adulto Jovem , Proteínas rap de Ligação ao GTP/genética , Proteínas rap de Ligação ao GTP/metabolismoRESUMO
PURPOSE: Spinal tuberculosis has been a common clinical extrapulmonary tuberculosis in recent years. The general anti-tuberculosis drug treatment cycle is long, with unsatisfactory efficacy. This study focused on the preparation and evaluation of rifapentine polylactic acid sustained-release microsphere complex for spinal tuberculosis therapy. METHODS: Rifapentine polylactic acid sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method, and RPSMs were combined with hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) composite material to obtain drug-loaded, sustained-release complex. We evaluated the complex for dynamics of drug release and osteogenic ability using in vitro release test, alkaline phosphatase and alizarin red staining, real-time PCR and Western blot. A rabbit model of a spinal tuberculosis defect was established and repaired using HA/ß-TCP or complex. The ability of anti-tuberculosis and tissue repair effects of the complex were evaluated through in vivo experiments. RESULTS: The complex constructed of RPSMs and HA/ß-TCP demonstrated a long drug release time, with no significant inhibition of cell osteogenic differentiation in vitro experiments. Postoperative macroscopic observation, immunohistochemical staining and Nilsson histological scores showed that the complex has good effects on the tissue repair. Moreover, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), important indexes of inflammation, decreased to normal levels in the complex group. CONCLUSION: In vitro and in vivo experiments demonstrated that the complex constructed of RPSMs and HA/ß-TCP effectively treated spinal tuberculosis. Therefore, the complex represents a promising approach for the treatment of spinal tuberculosis.
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Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.
Assuntos
Infecções por Herpesviridae , Herpesvirus Humano 8/metabolismo , Osteossarcoma , Adolescente , Adulto , Antígenos Virais/metabolismo , Criança , Pré-Escolar , China/epidemiologia , China/etnologia , DNA Viral/metabolismo , Feminino , Genoma Viral , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/etnologia , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Osteossarcoma/epidemiologia , Osteossarcoma/etnologia , Osteossarcoma/metabolismo , Osteossarcoma/virologia , Prevalência , Proteínas Virais/metabolismoRESUMO
BACKGROUND: Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The poor response to antitubercular agents necessitates the long-term use of high drug doses, resulting in low patient compliance, which is the main reason for chemotherapy failure and contributes to the development of multidrug-resistant TB. Patient non-compliance has been a major obstacle in the successful management of TB. The aim of this work was to develop and characterise rifapentine (RPT)-loaded PLGA-based nanoparticles (NPs) for reducing dosing frequency. METHODS: RPT-loaded PLGA and PLGA-PEG NPs were prepared using premix membrane homogenisation combined with solvent evaporation method. The resulting NPs were characterised in terms of physicochemical characteristics, toxicity, cellular uptake and antitubercular activity. NPs were further evaluated for pharmacokinetic and biodistribution studies in mice. RESULTS: The resulting NPs showed suitable and safe physicochemical characteristics and could be taken up by macrophages. RPT-loaded NPs were more effective against Mycobacterium tuberculosis than free RPT. In vivo studies revealed that NPs could improve pharmacokinetic parameters, particularly for RPT/PLGA-PEG NPs. Moreover, both formulations had no toxicity to the organs of mice and could reduce hepatotoxicity. CONCLUSION: The application of PLGA-based NPs as sustained-release delivery vehicles for RPT could prolong drug release, modify pharmacokinetics, increase antitubercular activity and diminish toxicity, thereby allowing low dosage and frequency.
Assuntos
Antituberculosos/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Nanopartículas/administração & dosagem , Rifampina/análogos & derivados , Administração Oral , Animais , Antituberculosos/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hemólise/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Prostaglandinas A/química , Rifampina/administração & dosagem , Rifampina/farmacocinética , Distribuição TecidualRESUMO
BACKGROUND: This study aimed to develop and evaluate a sustained drug delivery system for the treatment of osteoarticular tuberculosis (TB) to address the issues surrounding low drug concentration in lesions and bone defects or nonunion after debridement. METHODS: The effects of rifapentine on the proliferation and cell cycle of bone marrow mesenchymal stem cells (BMSCs) were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry. Rifapentine polylactic acid (PLA) sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method and investigated the antibacterial activity in vitro. In this study, two sustained drug delivery systems were prepared by integrating RPSMs and BMSCs into hydroxyapatite/ß-tricalcium phosphate (HA/ß-TCP) or allogeneic bone. We evaluated these drug delivery systems for dynamics of drug release and osteogenic ability by in vitro release test, alkaline phosphatase (ALP) and alizarin red staining, and real-time PCR. RESULTS: The results showed that rifapentine concentrations up to 45.0 µg/mL had no effect on cell proliferation and cell cycle. The encapsulation and drug loading efficiency of the fabricated RPSMs were 78.11%±1.16% and 35.57%±0.85%, respectively. The RPSMs had uniform particle size distribution and a long-term anti-bacterium effect. The HA/ß-TCP-implanted drug delivery system was found to be more effective in reducing the burst release and having a longer duration of sustained release and retention compared to allogeneic bone. The ALP and alizarin red staining and real-time PCR results showed that it had excellent osteoconductive and osteoinductive properties. CONCLUSIONS: In conclusion, the sustained drug delivery system with HA/ß-TCP as scaffold material represents a potential new strategy for TB infections and bone defects.
Assuntos
Antituberculosos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Rifampina/análogos & derivados , Tuberculose Osteoarticular/tratamento farmacológico , Animais , Diferenciação Celular , Proliferação de Células , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Citometria de Fluxo , Osteogênese/efeitos dos fármacos , Coelhos , Rifampina/farmacologiaRESUMO
OBJECTIVE: Spinal hydatid disease is rare and remains a serious health problem associated with high rates of recurrence. We report our experience in treating patients with thoracic spinal hydatidosis through a single-center case-series study. METHODS: Sixteen patients with thoracic spinal hydatidosis were treated in our center between 1995 and 2017. A total en bloc spondylectomy (TES) was performed in three patients. Five patients were treated with posterior decompression and stabilization after removing the involved elements. The remaining patients underwent curettage and resection of the infected bone. The therapy was completed with medical treatment or radiotherapy. RESULTS: Of the 16 patients, seven were men and nine were women; their mean age was 38.5 years (range 28-60 years). The infected area was the upper thoracic level in one patient, mid thoracic level in eight patients, and lower thoracic level in seven patients. Four patients had paraplegia and seven had paraparesis before surgery. At the last follow-up, five patients had successfully recovered from the neurological damage. During a mean follow-up of 4.75 years (range 2-12 years), eight patients had local recurrence; however, no patient who underwent TES had recurrence. CONCLUSIONS: An individualized surgical strategy should be decided carefully for each patient in the first intervention. In the early stages of the disease, TES should be considered as a treatment for suitable cases of primary thoracic spinal hydatidosis.
Assuntos
Equinococose/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Procedimentos de Cirurgia Plástica , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Low drug concentration in the tuberculosis (TB) lesion and bone defects or nonunion after debridement are two major problems that occur in the course of treating osteo-articular TB. Thus, the combination of drug-delivery system and bone tissue repair appears to be the most promising option for osteoarticular TB treatment. MATERIALS AND METHODS: Herein, we report a novel anti-TB dual delivery system based on rifapentine polylactic acid microspheres (RPMs) to treat infections, with the addition of adipose-derived mesenchymal stem cells (ASCs) seeded in hydroxyapatite/tricalcium phosphate (HA/TCP) to promote bone formation. Cell proliferation, osteogenesis, and apoptosis were performed to investigate the effects of rifapentine on ASCs. The RPMs were synthesized by emulsion-solvent evaporation method, and then the monolayer composite (ASC + RPM) and three-dimensional (3D) composite scaffold (ASC + RPM + HA/TCP) were constructed, respectively. The alkaline phosphatase (ALP) activity and real-time PCR were used for determining the osteogenic differentiation. The concentrations of rifapentine resulting from the composites were detected. RESULTS: The results showed that rifapentine has no influence on ASCs proliferation and osteogenesis when the drug concentration was below 20 µg/mL, which was significantly higher than minimal inhibitory concentration. The drug loading and encapsulation efficiency of RPMs were 40.56%±2.63% and 70.24%±2.18%, respectively. The proliferation of the cells in monolayer was higher than that in 3D composite, and the addition of RPMs slightly increased the proliferation. The ALP activity and gene expression of osteocalcin and osteopontin were higher in the 3D composite than those in the monolayer. Good biocompatibility was observed by microscopic image and H&E stain. The release tests revealed that the 3D composite exhibited sustained release profiles of rifapentine for 76 days. The dual delivery systems in 3D composite could moderate the burst release and extend the length of release time when compared to single delivery in monolayers. CONCLUSION: In conclusion, such dual delivery antituberculotic scaffold represents a potential new strategy for TB infections and bone defects.