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BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.
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Fixação Interna de Fraturas , Vértebras Lombares , Procedimentos Cirúrgicos Robóticos , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Vértebras Torácicas , Humanos , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Espondilite Anquilosante/cirurgia , Espondilite Anquilosante/complicações , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Resultado do Tratamento , Idoso , Duração da Cirurgia , Tempo de Internação , Parafusos Pediculares , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , SeguimentosRESUMO
BACKGROUND: We evaluated the treatment response and predictive factors for overall survival (OS) in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT), who underwent stereotactic body radiotherapy (SBRT). Additionally, we developed and validated a personalised prediction model for patient survival. METHODS: Clinical information was retrospectively collected for 80 patients with HCC and PVTT, who were treated with SBRT at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) between December 2015 and June 2019. A multivariate Cox proportional hazard regression model was used to identify the independent predictive factors for survival. Clinical factors were subsequently presented in a nomogram. The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to evaluate the accuracy of the model and the net clinical benefit. RESULTS: All patients completed the planned radiotherapy treatment, and the median follow-up duration was 10 months (range, 1-35.3 months). The median survival duration was 11.5 months, with 3-, 6-, and 12-month survival rates of 92.5, 74.5, and 47.5%, respectively. The multivariable Cox regression model indicated that the following were significant independent predictors of OS: clinical T stage (p = 0.001, hazard ratio [HR] = 3.085, 95% confidence interval [CI]: 1.514-6.286), cirrhosis (p = 0.014, HR = 2.988, 95% CI: 1.246-7.168), age (p = 0.005, HR = 1.043, 95% CI: 1.013-1.075), alpha-fetoprotein level (p = 0.022, HR = 1.000, 95% CI: 1.000-1.000), and haemoglobin level (p = 0.008, HR = 0.979, 95% CI: 0.963-0.994). A nomogram based on five independent risk factors and DCA demonstrated a favourable predictive accuracy of patient survival (AUC = 0.74, 95% CI: 0.63-0.85) and the clinical usefulness of the model. CONCLUSIONS: SBRT is an effective treatment for patients with HCC with PVTT. Notably, clinical T stage, presence of cirrhosis, age, alpha-fetoprotein levels, and haemoglobin levels are independent prognostic factors for survival. The presented nomogram can be used to predict the survival of patients with HCC and PVTT, who underwent SBRT.
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Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/radioterapia , Veia Porta/patologia , Radiocirurgia/métodos , Trombose Venosa/radioterapia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Nomogramas , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Trombose Venosa/mortalidadeRESUMO
VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore critical to have a better understanding of VEGF-B function and the underlying mechanisms. Here, using comprehensive methods and models, we have identified VEGF-B as a potent antioxidant. Loss of Vegf-b by gene deletion leads to retinal degeneration in mice, and treatment with VEGF-B rescues retinal cells from death in a retinitis pigmentosa model. Mechanistically, we demonstrate that VEGF-B up-regulates numerous key antioxidative genes, particularly, Gpx1 Loss of Gpx1 activity largely diminished the antioxidative effect of VEGF-B, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B. In addition, we found that the antioxidant function of VEGF-B is mediated mainly by VEGFR1. Given that oxidative stress is a crucial factor in numerous human diseases, VEGF-B may have therapeutic value for the treatment of such diseases.
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Antioxidantes/metabolismo , Degeneração Retiniana/genética , Fator B de Crescimento do Endotélio Vascular/metabolismo , Animais , Anticorpos Neutralizantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Estresse Oxidativo , Retina/efeitos dos fármacos , Retina/patologia , Degeneração Retiniana/tratamento farmacológico , Retinose Pigmentar/genética , Fator B de Crescimento do Endotélio Vascular/genética , Fator B de Crescimento do Endotélio Vascular/farmacologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Glutationa Peroxidase GPX1RESUMO
Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti-VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases.
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Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Caveolina 1/fisiologia , Neovascularização de Coroide/prevenção & controle , MAP Quinase Quinase 4/metabolismo , Fragmentos de Peptídeos/farmacologia , Neovascularização Retiniana/prevenção & controle , Animais , Caveolina 1/farmacologia , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Quimioterapia Combinada , Humanos , Camundongos Knockout , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
Neovascular diseases, such as many cancers and ocular disorders, are life threatening and devastating. Although anti-vascular endothelial growth factor A (VEGF-A) therapy is available, many patients are not responsive and drug resistance can develop. To try to overcome these problems, combination therapy targeting VEGF-A and platelet-derived growth factor B (PDGF-B) was tested. However, one obvious drawback was that the other VEGF and PDGF family members were not inhibited and therefore could compensate. Indeed, this was, at least to some extent, demonstrated by the disappointing outcomes. To this end, we designed novel multi-targeted inhibitors that can block most of the VEGF and PDGF family members simultaneously by making a fusion protein containing the ligand-binding domains of vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor beta (PDGFRß), which can therefore act as a decoy blocker for most of the VEGF and PDGF family members. Indeed, in cultured cells, the novel inhibitors suppressed the migration and proliferation of both vascular endothelial cells and smooth muscle cells, and abolished VEGFR2 and PDGFRß activation. Importantly, in a choroidal neovascularization model in vivo, the novel inhibitor inhibited ocular neovascularization more efficiently than the mono-inhibitors against VEGFR or PDGFR alone respectively. Mechanistically, a genome-wide microarray analysis unveiled that the novel inhibitor regulated unique sets of genes that were not regulated by the mono-inhibitors, further demonstrating the functional uniqueness and superiority of the novel inhibitor. Together, we show that the multi-targeted inhibitors that can block VEGFR1, VEGFR2 and PDGFRß simultaneously suppress pathological angiogenesis more efficiently than monotherapy, and may therefore have promising therapeutic value for the treatment of neovascular diseases.
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Inibidores da Angiogênese/uso terapêutico , Olho/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Proteínas Recombinantes de Fusão/uso terapêutico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Olho/irrigação sanguínea , Olho/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Transcriptoma/efeitos dos fármacos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is rare, but a certain amount of mortality remains in NPC patients. Our study aimed to identify candidate genes as biomarkers for NPC screening, diagnosis, and therapy. METHODS: We investigated two microarray profile datasets GSE64634 and GSE12452 to screen the potential differentially expressed genes (DEGs) in NPC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were also performed. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. The associated transcriptional factor regulatory network of the DEGs was also constructed. RESULTS: A total of 152 DEGs were identified from the GSE64634 and GSE12452 datasets, including 10 upregulated and 142 downregulated genes. Gene functional enrichment analysis indicated that these DEGs were enriched in the cilium movement, antimicrobial humoral response, O-glycan processing, mucosal immune response, carbohydrate transmembrane transporter activity, hormone biosynthetic process, neurotransmitter biosynthetic process, and drug metabolism-cytochrome P450 pathway. Five hub genes (DNALI1, RSPH4A, RSPH9, DNAI2, and ALDH3A1) and one significant module (score = 5.6) were obtained from the PPI network. Key transcriptional factors, such as SPI1, SIN3B, and GATA2, were identified with close interactions with these five hub DEGs from the gene-transcriptional factor network. CONCLUSIONS: With the integrated bioinformatic analysis, numerous DEGs related to NPC were screened, and the hub DEGs we identified may be potential biomarkers for NPC.
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Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Carcinoma Nasofaríngeo/genética , Fatores de Transcrição/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Prognóstico , Mapas de Interação de Proteínas , Software , Fatores de Transcrição/metabolismoRESUMO
There is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin-loaded poly(ε-caprolactone) (PCL)-Pluronic micelles and miR-34a to better combat esophageal cancer. Doxorubicin was loaded into PCL-Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL-Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL-Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin-loaded PCL-Pluronic micelles and miR-34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin-loaded PCL-Pluronic micelle and miR-34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.
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Doxorrubicina/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Poliésteres/química , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Feminino , Camundongos , Camundongos Nus , MicelasRESUMO
Undersized fraction from aged municipal solid waste (UFAMSW), as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants. The characteristics and effectiveness of heavy metal pollution removal in UFAMSW attracted tremendous research interest from scientists recently. In this study, the heavy metal removal efficiencies and bioavailability of washing on contaminated UFAMSW were evaluated with three washing reagents including ethylene diamine tetra acetic acid (EDTA), citric acid (CA), and humic acid (HA). The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and response surface methodology (RSM) was employed to optimize the washing conditions. The results indicated that the removal efficiencies of Cu, Zn, and Mn could be 53.68%, 52.12%, and 30.63% by EDTA/HA washing and 42.36%, 39.67% and 28.49% by CA/HA washing, respectively. The European Community Bureau of Reference (BCR) sequential extraction was applied to analyze the fraction change of heavy metals in UFAMSW before and after washing, and it was found that chelating agent combined with HA could contribute to the removal of the exchangeable fraction. Physical and chemical properties of UFAMSW were improved to some extent after washing with mixed HA and chelating agent and could achieve the quality standard of landscape gardening soil. Accordingly, the mixture of HA and other chelating agents could be a promising washing process for preparation of landscape gardening soil using UFAMSW.Implications: Our manuscript studies the removal of heavy metals from the contaminated undersized fraction from aged municipal solid waste (UFAMSW). UFAMSW, as a kind of soil-like material, has been proved effective in providing a large amount of organic matter and nutrients for soil and plants however often limited by heavy metal pollution. The UFAMSW used in this experiment was collected after the excavation and screening-sorting of aged refuse from Changshankou Domestic Waste Sanitary Landfill in Wuhan City, Hubei Province, Southern China. This study investigated the effects of EDTA, CA, HA, mixed EDTA/HA, and mixed CA/HA washing on heavy metal removal (Cu, Zn, and Mn), bioavailability of residual heavy metal and properties. The effects of chelating agent concentration, pH, and washing time on metal removal were investigated and then response surface methodology was employed to optimize the washing conditions. The results showed that washing by CA/HA and EDTA/HA, had a higher removal efficiency of heavy metals (Cu, Zn, and Mn) in UFAMSW compared to single HA. Meanwhile, HA has a higher removal for exchangeable fraction of heavy metals, the exchangeable concentration of Cu, Zn, and Mn in CA/HA and EDTA/HA washed UFAMSW were lower compared with UFAMSW washed by single CA and EDTA. Thus, mixing HA with EDTA or CA makes a less risk to environmental and the removal efficiency is acceptable. Additionally, CA/HA and EDTA/HA washing tend to improve soil physicochemical properties and soil fertility. Thus, mixing HA with different washing agent are potential methods for preparation of landscape gardening soil using UFAMSW.
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Metais Pesados , Poluentes do Solo , Ácido Edético/química , Substâncias Húmicas , Solo/química , Ácido Acético , Ácido Cítrico/química , Jardinagem , Resíduos Sólidos , Poluentes do Solo/análise , Quelantes/química , Metais Pesados/análiseRESUMO
Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract (NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive (Calb1+) NTS neurons that are molecularly distinct from Tac1+ neurons. These Calb1+ neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+ NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.
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PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.
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Estadiamento de Neoplasias , Neoplasias da Língua , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/mortalidade , Idoso , Estudos Retrospectivos , Prognóstico , Radioterapia Adjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapiaRESUMO
Intervertebral disc degeneration (IDD)-induced low back pain significantly influences the quality of life, placing a burden on public health systems worldwide. Currently available therapeutic strategies, such as conservative or operative treatment, cannot effectively restore intervertebral disc (IVD) function. Decellularized matrix (DCM) is a tissue-engineered biomaterial fabricated using physical, chemical, and enzymatic technologies to eliminate cells and antigens. By contrast, the extracellular matrix (ECM), including collagen and glycosaminoglycans, which are well retained, have been extensively studied in IVD regeneration. DCM inherits the native architecture and specific-differentiation induction ability of IVD and has demonstrated effectiveness in IVD regeneration in vitro and in vivo. Moreover, significant improvements have been achieved in the preparation process, mechanistic insights, and application of DCM for IDD repair. Herein, we comprehensively summarize and provide an overview of the roles and applications of DCM for IDD repair based on the existing evidence to shed a novel light on the clinical treatment of IDD.
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Water kefir, a natural and stable functional microbiota system consisting of a symbiotic mixture of probiotics, shows multiple bioactivities but little is known about the effect of water kefir microbiota on the prevention of inflammatory bowel disease (IBD), which is one of the most common intestinal problems and has become a worldwide public health concern. Here, the main objectives of the present study were to investigate the preventative effects of water kefir microbiota, a probiotic consortium mainly consisting of bacteria belonging to Acetobacter, Lactobacillus, and Komagataeibacter and fungi belonging to Saccharomyces and Talaromyces, in a dextran sodium sulfate (DSS)-induced colitis mouse model and unveil the underlying mechanism of the action. Water kefir microbiota effectively improved the disease severity of DSS-induced colitis, including decreased body weight and colon length, increased spleen index and DAI score, and colonic tissue damage. Moreover, water kefir microbiota restored the abnormal expression of tight junction proteins (such as occludin, ZO-1, and claudin-1) and pro-inflammatory and anti-inflammatory cytokines (such as IL-1ß, IL-6, TNF-α, COX-2, iNOS, and IL-10) and inactivated TLR4-MyD88-NF-κB pathway induced by DSS. Water kefir microbiota also improved the composition and metabolism of intestinal microbiota. These findings demonstrated that water kefir microbiota could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis, which will be helpful for the development of water kefir microbiota-based microbial products as an alternative preventative strategy for IBD.
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Colite , Doenças Inflamatórias Intestinais , Kefir , Microbiota , Camundongos , Animais , Colite/metabolismo , Colo/metabolismo , Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Cognitive impairment (CI) is a common neurological disease resulting from traumatic brain injury (TBI). Trigeminal nerve stimulation (TNS) is an emerging, non-invasive, and effective neuromodulation therapy especially for patients suffering from brain function disorders. However, the treatment and recovery mechanisms of TNS remain poorly understood. By using combined advanced technologies, we revealed here that the neuroprotective potential of TNS to improve CI caused by TBI. The study results found that 40 Hz TNS treatment has the ability to improve CI in TBI mice and communicates with central nervous system via the trigeminal ganglion (TG). Transsynaptic virus experiments revealed that TG is connected to the hippocampus (HPC) through the corticotropin-releasing hormone (CRH) neurons of paraventricular hypothalamic nucleus (PVN) and the dopamine transporter (DAT) neurons of substantia nigra pars compacta/ventral tegmental area (SNc/VTA). Mechanistically, the data showed that TNS can increase the release of dopamine in the HPC by activating the following neural circuit: TGâCRH+ PVNâDAT+ SNc/VTA â HPC. Bulk RNA sequencing confirmed changes in the expression of dopamine-related genes in the HPC. This work preliminarily explains the efficacy and mechanism of TNS and adds to the increasing evidence demonstrating that nerve stimulation is an effective method to treat neurological diseases.
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Lesões Encefálicas Traumáticas , Dopamina , Camundongos , Animais , Dopamina/metabolismo , Substância Negra/metabolismo , Neurônios Dopaminérgicos/metabolismo , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/metabolismo , Nervo Trigêmeo/metabolismo , Hipocampo/metabolismo , CogniçãoRESUMO
OBJECTIVE: Because of rapid alterations in lifestyle and the incidence of metabolic syndrome (MetS), the prevalence of carotid atherosclerosis (CA) and carotid plaque (CP) may increase in China. We aimed to evaluate the prevalence of CA and CP as well as its relation to MetS in an East Chinese population. METHODS: The study included 6142 subjects who underwent general health screening including carotid ultrasonography in 2009. Diagnoses of MetS were made according to the revised Adult Treatment Panel III criteria. RESULTS: The prevalence of CA and CP increased gradually with age. These conditions were more prevalent in men than in women (CA: 22.1%vs 12.0%, P < 0.001; CP: 12.6%vs 7.2%, P < 0.001). Multivariate logistic regression analysis showed that male gender, age, blood pressure, fasting blood glucose (FBG) and low-density lipoprotein cholesterol were risk factors for CA and CP, while high-density lipoprotein cholesterol was protective for CA. Age ≥ 50 years has the largest impact on CA and CP, followed by elevated blood pressure and elevated blood glucose. Individuals with MetS had a higher prevalence of CA (27.7%vs 20.0% in men, 24.0%vs 10.3% in women; P < 0.001 in both) and CP (16.6%vs 11.2% in men, P < 0.001; 11.8%vs 6.5% in women, P < 0.005) than those without MetS. The prevalence and odds ratios of CA and CP aggregated with an increasing number of MetS components, even in individuals exhibiting only one component. CONCLUSIONS: These results indicate that CA and CP have become a major public health problem in China. MetS and its components were associated with an increased prevalence of CA and CP.
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Doenças das Artérias Carótidas/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Adulto JovemRESUMO
Bacterial infections can compromise the physical and biological functionalities of humans and pose a huge economical and psychological burden on infected patients. Nitric oxide (NO) is a broad-spectrum antimicrobial agent, whose mechanism of action is not affected by bacterial resistance. S-nitrosoglutathione (GSNO), an endogenous donor and carrier of NO, has gained increasing attention because of its potent antibacterial activity and efficient biocompatibility. Significant breakthroughs have been made in the application of GSNO in biomaterials. This review is based on the existing evidence that comprehensively summarizes the progress of antimicrobial GSNO applications focusing on their anti-infective performance, underlying antibacterial mechanisms, and application in anti-infective biomaterials. We provide an accurate overview of the roles and applications of GSNO in antibacterial biomaterials and shed new light on the avenues for future studies.
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Silicosis is one of the most serious occupational diseases with the main feature of inflammatory cell infiltration, fibroblasts activation, and large deposition of extracellular matrix in the lung. Increasing evidence indicates that macrophage-derived exosomes may play an important role in the development of silicosis by transferring their loaded microRNAs (miRNAs). Hence we carried out high-throughput sequencing to identify the expression of exosomal miRNA from macrophages exposed to silica or not in the previous study. Then we verified that miR-7219-3p was significantly up-regulated in macrophages and their exosomes after silica-exposure, as well as in the silicotic mice model by qRT-PCR, subsequent experiments confirmed that the increase of miR-7219-3p facilitated fibroblast to myofibroblast trans-differentiation (FMT), as well as cell proliferation and migration. Spouty1 (SPRY1), which served as a negative modulator of the Ras/ERK/MAPK signaling pathway, was verified as the target gene of miR-7219-3p, the knockdown or over-expression of SPRY1 apparently promoted or inhibited FMT via the Ras/ERK/MAPK signaling pathway. Furthermore, the inhibition of exosomal miR-7219-3p partially suppressed FMT and silica-induced pulmonary fibrosis in vitro and in vivo. In brief, our results demonstrated that exosomal miR-7219-3p played an important role in FMT and might be a novel therapeutic target of silicosis.
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Exossomos , MicroRNAs , Silicose , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Transdiferenciação Celular , Exossomos/genética , Fibroblastos/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Silicose/genéticaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a worldwide disease characterized by the chronic and irreversible decline of lung function. Currently, there is no drug to successfully treat the disease except for lung transplantation. Numerous studies have been devoted to the study of the fibrotic process of IPF and findings showed that transforming growth factorß1 (TGFß1) plays a central role in the development of IPF. TGFß1 promotes the fibrotic process of IPF through various signaling pathways, including the Smad, MAPK, and ERK signaling pathways. There are intersections between these signaling pathways, which provide new targets for researchers to study new drugs. In addition, TGFß1 can affect the fibrosis process of IPF by affecting oxidative stress, epigenetics and other aspects. Most of the processes involved in TGFß1 promote IPF, but TGFß1 can also inhibit it. This review discusses the role of TGFß1 in IPF.
Assuntos
Fibrose Pulmonar Idiopática/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Humanos , Fibrose Pulmonar Idiopática/terapia , Sistema de Sinalização das MAP Quinases , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
BACKGROUND: Breast cancer (BRCA) is the most common tumor in women, and lipid metabolism involvement has been demonstrated in its tumorigenesis and development. However, the role of lipid metabolism-associated genes (LMAGs) in the immune microenvironment and prognosis of BRCA remains unclear. METHODS: A total of 1076 patients with BRCA were extracted from The Cancer Genome Atlas database and randomly assigned to the training cohort (n = 760) or validation cohort (n = 316). Kaplan-Meier analysis was used to assess differences in survival. Consensus clustering was performed to categorize the patients with BRCA into subtypes. Using multivariate Cox regression analysis, an LMAG-based prognostic risk model was constructed from the training cohort and validated using the validation cohort. The immune microenvironment was evaluated using the ESTIMATE and tumor immune estimation resource algorithms, CIBERSORT, and single sample gene set enrichment analyses. RESULTS: Consensus clustering classified the patients with BRCA into two subgroups with significantly different overall survival rates and immune microenvironments. Better prognosis was associated with high immune infiltration. The prognostic risk model, based on four LMAGs (MED10, PLA2G2D, CYP4F11, and GPS2), successfully stratified the patients into high- and low-risk groups in both the training and validation sets. High risk scores predicted poor prognosis and indicated low immune status. Subgroup analysis suggested that the risk model was an independent predictor of prognosis in BRCA. CONCLUSION: This study demonstrated, for the first time, that LMAG expression plays a crucial role in BRCA. The LMAG-based risk model successfully predicted the prognosis and indicated the immune microenvironment of patients with BRCA. Our study may provide inspiration for further research on BRCA pathomechanisms.
RESUMO
BACKGROUND: Whether there is any clinical superiority for the two-incision total hip arthroplasty (THA) over the mini-posterior THA remains controversial. The present meta-analysis aimed to comprehensively compare the clinical outcomes between the two mini-invasive THAs. METHODS: Two authors searched the database of Web of Science, PubMed, EMBASE and Cochrane Library to screen eligible studies individually. The quality evaluation of included studies was performed according to the principle of risk-of-bias of the Cochrane Library. The pooled results were analysed by Review Manager 5.3 software. RESULTS: A total of seven prospective studies (including five randomized controlled trials) with 423 hips were finally included for meta-analysis. The pooled results revealed that the mini-posterior THA outperformed the two-incision THA in shortening operative times, reducing blood loss and postoperative fracture risks, while no significant difference was found between the two surgery methods with respect to HSS scoring, SF-12 scoring, postoperative function recovery and other postoperative complications. CONCLUSION: Based on the pooled results, we suggested the mini-posterior THA as a preferable choice for patients suffering from severe advanced hip diseases.
Assuntos
Artroplastia de Quadril , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do TratamentoRESUMO
ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65âyears and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, Pâ=â.002), while no significant difference was observed in CSS (61.8% vs 51.7%, Pâ=â.074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65âyears and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.