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BACKGROUND: There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures. METHODS: We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient's vertebral body was determined. RESULTS: In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm3, with T12 having the lowest BMD (p < 0.001, T12 vs. L2). Cancellous BMD ranged from 128.5 ± 58.4 to 140.9 ± 58.9 mg/cm3, with L3 having the lowest BMD. OVCF patients had lower cortical BMD of 365.0 ± 78.9 to 429.3 ± 156.7 mg/cm3, with a further decrease in T12 BMD. Cancellous BMD ranged from 71.68 ± 52.07 to 123.9 ± 126.2 mg/cm3, with L3 still having the lowest BMD. Fractured vertebrae in OVCF patients (T12, L1, and L2) had lower cortical bone density compared to their corresponding vertebrae without fractures (p < 0.05). CONCLUSIONS: T12 had the lowest cortical BMD and L3 had the lowest cancellous BMD in OVCF patients, with T12 also having the highest incidence of osteoporotic fractures. These findings suggest that reduction in cortical BMD has a greater impact on OVCF than reduction in cancellous BMD, along with biomechanical factors.
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Densidad Ósea , Hueso Cortical , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Tomografía Computarizada por Rayos X , Humanos , Femenino , Anciano , Masculino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Hueso Cortical/diagnóstico por imagen , Factores de Riesgo , Anciano de 80 o más Años , Cuerpo Vertebral/diagnóstico por imagen , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/etiología , Osteoporosis/diagnóstico por imagenRESUMEN
OBJECTIVE: We aimed to explore the prognostic significance of preoperative magnetic resonance imaging (MRI) variables and novel inflammatory indicators in predicting neurological recovery post-cervical traumatic spinal cord injury (TSCI) in the study. METHODS: We enrolled a total of 244 patients diagnosed with acute cervical TSCI from 2 hospitals and evaluated the prognostic value of MRI variables (intramedullary hemorrhage, intramedullary lesion length [IMLL], maximum spinal cord compression, and maximum canal compromise [MCC]) and novel inflammatory indicators (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune-inflammatory index) in patients with acute cervical TSCI. RESULTS: Among the 244 patients, 140 (57.38%) exhibited improved AIS grade conversion at 1-year follow-up. The results revealed intramedullary hemorrhage, IMLL, MCC, neutrophils, and NLR were significantly different compared with follow-up AIS grade. Furthermore, IMLL, MCC, white blood cells, neutrophils, NLR, and lymphocyte-to-monocyte ratio correlated with the follow-up AIS grade by Spearman's correlation analysis. Multivariate analysis showed IMLL, intramedullary hemorrhage, NLR, and admission AIS grade emerged as independent predictors of AIS grade conversion. The receiver operating characteristic curve analysis showed that the novel model (combination of MRI variables, NLR, and admission AIS grade) produced a larger area under the curve compared with using only intramedullary hemorrhage, IMLL, NLR, or admission AIS grade individually. CONCLUSION: Intramedullary hemorrhage and IMLL and NLR are predictors of AIS grade conversion after cervical TSCI. Therefore, we suggest the combination of MRI variables and NLR for the prognostic prediction of AIS grade conversion in patients with cervical TSCI.
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Degradation and interference of the nucleic acid probes in complex biological environments like cytoplasm or body fluid can cause obvious false-positive signals and inefficient bioregulation in biosensing and biomedicine. To solve this problem, here, we proposed a universal strategy, termed L-DNA assembly mirror-image box-based environment resistance (L-AMBER), to protect nucleic acid probes from degradation and maintain their responsive activity in complex biological environments. Strand displacement reaction (SDR), aptamer, or DNAzyme-based D-DNA probes were encapsulated into an L-DNA box by using an L-D-L block DNA carrier strand to construct different kinds of L-AMBER probes. We proved that the L-DNA box could effectively protect the encapsulated D-DNA probes by shielding the interference of complex biological environments and only allowing small target molecules to enter for recognition. Compared with the D-AMBER probes, the L-AMBER probes can realize DNase I-assisted amplification detection of biological samples, low false-positive bioimaging, and highly efficient miRNA silence in living cells. Therefore, L-AMBER provided a universal and effective strategy for enhancing the resistance to environmental interference of nucleic acid probes in biosensing and biomedicine applications.
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ADN , Humanos , ADN/química , ADN/genética , Técnicas Biosensibles , MicroARNs/genética , MicroARNs/análisis , Desoxirribonucleasa I/metabolismo , ADN Catalítico/química , ADN Catalítico/metabolismo , Sondas de Ácido Nucleico/química , Células HeLa , Sondas de ADN/químicaRESUMEN
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
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PURPOSE: The aim of the study was to evaluate the feasibility of a bioabsorbable cage consisting of magnesium and magnesium phosphate cement (MPC) in a porcine lumbar interbody fusion model. METHODS: Twelve male Ba-Ma mini pigs underwent lumbar discectomy and fusion with an Mg-MPC cage or a PEEK cage at the L3/L4 and L4/L5 level. Computed tomography (CT) scans were made to evaluate the distractive property by comparing average disc space height (DSH) before and at 6, 12, and 24 weeks after the operation. After the lumbar spines were harvested at 6 or 24 weeks after the operation, micro-CT examination was conducted to analyze the fusion rate, and stiffness of motion segments was investigated through mechanical tests. A histological study was performed to evaluate the tissue type, inflammation, and osteolysis in the intervertebral space. RESULTS: CT scans showed no significant difference between the two groups in average DSH at each time point. Micro-CT scans revealed an equal fusion rate in both groups (0% at 6 weeks, 83.3% at 24 weeks). Both groups showed time-dependent increases in stability, the Mg-MPC cages achieved an inferior stiffness at 6 weeks and a comparable stiffness at 24 weeks. Histologic evaluation showed the presence of newly formed bone in both groups. However, empty spaces were observed at the interface or around the Mg-MPC cages. CONCLUSION: Compared with the PEEK cages, the Mg-MPC cages achieved comparable distraction, fusion rate, and spinal stability at 24 weeks after the operation. However, due to inferior stiffness at the early stage and fast degradation, further modification of material composition and design are necessary.
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Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.
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Péptido Relacionado con Gen de Calcitonina , Carcinoma Neuroendocrino , Células Dendríticas , Neoplasias de la Tiroides , Microambiente Tumoral , Microambiente Tumoral/inmunología , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/inmunología , Neoplasias de la Tiroides/patología , Péptido Relacionado con Gen de Calcitonina/metabolismo , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/metabolismo , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/inmunología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , AMP Cíclico/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neurotransmisores/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/farmacología , Análisis de la Célula IndividualRESUMEN
BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) caused by osteoporosis is a common clinical fracture type. There are many surgical treatment options for OVCF, but there is a lack of comparison among different options. Therefore, we counted a total of 104 cases of OVCF operations with different surgical plans, followed up the patients, and compared the surgical outcome indications before, after and during the follow-up. METHOD: 104 patients who underwent posterior osteotomy (Modified PSO, SPO, PSO, VCR) and kyphosis correction surgery at our hospital between April 2006 and August 2021 with a minimum follow-up period of 24 months were included. All cases were injuries induced by a fall incurred while standing or lifting heavy objects without high-energy trauma. The mean CT value was 71 HU, which was below 110 HU, indicating severe osteoporosis. The indications for surgery included gait disturbance due to severe pain with pseudarthrosis, increased kyphotic angle, and progressive neurological symptoms. Pre- and postoperative CL, TLK, TK, PrTK, TKmax, GK, LL, PI, SS, PT, SVA, TPA, were investigated radiologically. Additionally, We evaluated estimated blood loss, surgical time and perioperative symptom. RESULT: The results show, after operation, TLK (37.32 ± 10.61° vs. 11.01 ± 8.06°, P < 0.001), TK (35.42 ± 17.64° vs. 25.62 ± 12.24°, P < 0.001), TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001), SVA (44.91 ± 48.67 vs. 23.52 ± 30.21, P = 0.013), CL (20.23 ± 13.21° vs. 11.45 ± 9.85°, P = 0.024) and TPA (27.44 ± 12.76° vs. 13.91 ± 9.24°, P = 0.009) were improved significantly in modified Pedicle subtraction osteotomy (mPSO) after operation. During follow-up, TLK (37.32 ± 10.61° vs. 13.88 ± 10.02°, P < 0.001) and TKmax (49.71 ± 16.32° vs. 24.12 ± 13.34°, P < 0.001) were improved significantly in Modified PSO group. In additon, estimated blood loss (790.0 ± 552.2 ml vs. 987.0 ± 638.5 ml, P = 0.038), time of operation (244.1 ± 63.0 min vs. 292.4 ± 87.6 min, P = 0.025) were favorable in Modified PSO group compared to control group. CONCLUSION: To conclude, mPSO could acquire a favorable degree of kyphosis correction as well as fewer follow-up complications. Compared with other surgical methods, it also has the advantages of less surgical trauma and shorter operation time. It can be an effective solution for the treatment of OVCF.
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Fracturas por Compresión , Fracturas Osteoporóticas , Osteotomía , Fracturas de la Columna Vertebral , Humanos , Fracturas por Compresión/cirugía , Femenino , Masculino , Osteotomía/métodos , Anciano , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Cifosis/cirugía , Cifosis/etiologíaRESUMEN
BACKGROUND: The fusion rate, clinical efficacy, and complications of minimally invasive fusion surgery and open fusion surgery in the treatment of lumbar degenerative disease are still unclear. METHODS: We conducted a literature search using PubMed, Embase, Cochrane Library, CNKI, and WANFANG databases. RESULTS: This study included 38 retrospective studies involving 3097 patients. Five intervention modalities were considered: unilateral biportal endoscopic-lumbar interbody fusion (UBE-LIF), percutaneous endoscopic-lumbar interbody fusion (PE-LIF), minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF). Quality assessment indicated that each study met acceptable quality standards. PE-LIF demonstrated reduced low back pain (Odds Ratio = 0.50, Confidence Interval: 0.38-0.65) and lower complication rate (Odds Ratio = 0.46, Confidence Interval: 0.25-0.87) compared to PLIF. However, in indirect comparisons, PE-LIF showed the lowest fusion rates, with the ranking as follows: UBE-LIF (83.2%) > MIS-TLIF (59.6%) > TLIF (44.3%) > PLIF (39.8%) > PE-LIF (23.1%). With respect to low back pain relief, PE-LIF yielded the best results, with the order of relief as follows: PE-LIF (96.4%) > MIS-TLIF (64.8%) > UBE-LIF (62.6%) > TLIF (23.0%) > PLIF (3.2%). Global and local consistency tests showed satisfactory results, and heterogeneity tests indicated good stability. CONCLUSIONS: Compared to conventional open surgery, minimally invasive fusion surgery offered better scores for low back pain and Oswestry Disability Index, lower complication rates, reduced bleeding, and shorter hospital stays. However, minimally invasive fusion surgery did not show a significant advantage in terms of fusion rate and had a longer operative time.
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PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.
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Calcitonina , Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Calcitonina/sangre , Persona de Mediana Edad , Carcinoma Neuroendocrino/sangre , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/diagnóstico , Adulto , Pronóstico , Anciano , Cuidados Preoperatorios/métodosRESUMEN
INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.
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Recurrencia Local de Neoplasia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Adolescente , Masculino , Femenino , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Niño , Pronóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Adulto Joven , Metástasis Linfática/patología , Estudios de Seguimiento , Tiroidectomía , Adulto , PreescolarRESUMEN
Background: Anxiety symptoms are widely observed among the youth, and engagement in sports has been demonstrated to mitigate these symptoms. Nonetheless, the effectiveness of specific sports and the potential moderating role of psychological factors, such as self-esteem and self-efficacy, on the influence of sports on anxiety, remains to be elucidated. This study was designed to longitudinally assess the impact of sports participation on anxiety symptoms among young individuals. Methods: The study encompassed 163 university students, with a male predominance of 81.6%, and explored the influence of sport-related factors (such as mastery of table tennis skills, level and engagement) and psychological aspects (including self-efficacy, self-esteem and resilience) on anxiety symptoms, employing an 8-month longitudinal approach. Physical activity, sedentary and sleep behaviour, along with age, body mass index (BMI), and sex, were accounted for as confounding variables. Results: The study found that high table tennis performance score was found to buffer the development of anxiety symptoms in students with decreased self-esteem in an exploratory moderation model. Self-esteem and self-efficacy were negatively associated with the development of anxiety symptoms, whereas physical activity factors did not have a direct effect. Conclusion: This study highlights the potential of table tennis as a form of sport to alleviate anxiety symptoms in university students, particularly among those with decreased self-esteem. Future research should address the study's limitations and explore the potential moderating effects of other psychological factors. Overall, these findings suggest a potential new approach to treating anxiety symptoms among university students.
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OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.
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Sensibilidad y Especificidad , Neoplasias de la Tiroides , Ultrasonografía , Humanos , Masculino , Femenino , Neoplasias de la Tiroides/diagnóstico por imagen , Adulto , Estudios Retrospectivos , Ultrasonografía/métodos , Diagnóstico Diferencial , Persona de Mediana Edad , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/irrigación sanguíneaRESUMEN
Bioproduction of diverse N-acetyl chitooligosaccharides from chitin is of great value. In the study, a novel GH family 18 bifunctional chitinase gene (PsChi82) from Paenibacillus shirakamiensis was identified, expressed and biochemically characterized. PsChi82 was most active at pH 5.0, and 55 °C, and displayed remarkable pH stability with the broad pH range of 3.0-12.0. It showed high chitosanase activity of 10.6 U mg-1 and diverse hydrolysis products of GlcNAc, (GlcNAc)2, GlcN-GlcNAc and (GlcN)2-GlcNAc, which may facilitate comprehensively understanding of structure-function relationships of N-acetyl COSs. Three engineered variants were then expressed and characterized. Among them, PsChi82-CBM26 possessed specific activity of 25.1 U mg-1 against colloidal chitin, which was 2.1 folds higher than that of PsChi82. The diverse N-acetyl COSs were subsequently produced by PsChi82-CBM26 with a sugar content of 23.2 g L-1. These excellent properties may make PsChi82-CBM26 potentially useful for N-acetyl COSs production in the food and chemical industries.
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Proteínas Bacterianas , Quitina , Quitinasas , Quitosano , Oligosacáridos , Paenibacillus , Quitinasas/química , Quitinasas/genética , Quitinasas/metabolismo , Oligosacáridos/química , Oligosacáridos/metabolismo , Quitina/química , Quitina/análogos & derivados , Quitina/metabolismo , Quitosano/química , Quitosano/metabolismo , Paenibacillus/enzimología , Paenibacillus/genética , Paenibacillus/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Concentración de Iones de Hidrógeno , Estabilidad de Enzimas , Hidrólisis , Ingeniería de ProteínasRESUMEN
BACKGROUND: LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. METHODS: The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. RESULTS: We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. CONCLUSIONS: Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.
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Glioblastoma , MicroARNs , ARN Largo no Codificante , Animales , Femenino , Humanos , Masculino , Ratones , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/genética , Apoptosis , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismoRESUMEN
Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal-organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.
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Inflamación , Estructuras Metalorgánicas , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Superóxido Dismutasa/metabolismo , Porosidad , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Masculino , Ferroptosis/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Diabetes Mellitus Experimental , Nanopartículas/química , Humanos , Antioxidantes/farmacología , Nanocompuestos/química , Proteínas de la MembranaRESUMEN
The dried Mume fructus (MF) is a special food and herbal medicine with a long history of processing and application. The browning index (BI) of Prunus mume (PM) is pivotal in determining the medicinal value and edible quality of MF. Exploring the BI of PM holds significant importance for both the selection of PM varieties and understanding the formation mechanism of high-quality MF. This study systematically analyzed the physicochemical properties, BI, and quality indicators of four PM varieties (Qingzhu Mei, Yesheng Mei, Nangao Mei, and Zhaoshui Mei) after processing into MF. The results showed significant differences in eight physicochemical indicators among the four PM varieties (p < 0.05). Notably, Qingzhu Mei exhibited the highest titratable acid content, Nangao Mei had the most prominent soluble solid and soluble sugar content, and Zhaoshui Mei showed outstanding performance in reducing sugar, soluble protein, and free amino acids. Regarding drying characteristics, Yesheng Mei and Nangao Mei required a shorter drying time. In terms of BI, Nangao Mei exhibited the greatest degree of browning and its color appearance was darker. When considering quality evaluation, Nangao Mei excelled in rehydration ability and extract content, while Zhaoshui Mei demonstrated outstanding levels of total phenols, total flavonoids, and total antioxidant capacity. Overall, the evaluation suggested that the Nangao Mei variety was more suitable for MF processing. These research results provide a valuable theoretical foundation for understanding the BI of PM varieties and serve as a reference for the selection of PM varieties as raw materials for processing MF.
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BACKGROUND: The optimal treatment modality for upper lumbar disc herniation remains unclear. Herein, we compared the clinical efficacy and application value of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and transforaminal lumbar interbody fusion (TLIF) for upper lumbar disc herniation. We aimed to provide new evidence to guide surgical decisions for treating this condition. METHODS: We retrospectively analyzed the clinical data of 81 patients with upper lumbar disc herniation admitted between January 2017 and July 2018, including 41 and 40 patients who underwent MIS-TLIF and TLIF, respectively. Demographic characteristics, preoperative functional scores, perioperative indicators, and postoperative complications were compared. We performed consecutive comparisons of visual analog scale (VAS) scores of the lumbar and leg regions, Oswestry disability index (ODI), Japanese Orthopaedic Association scores (JOA), and MacNab scores at the final follow-up, to assess clinical outcomes 5 years postoperatively. RESULTS: VAS scores of the back and legs were significantly lower in the MIS-TLIF than the TLIF group at 3 months and 1 year postoperatively (P < 0.05). Intraoperative bleeding and postoperative hospitalization time were significantly lower, and the time to return to work/normal life was shorter in the MIS-TLIF than in the TLIF group (P < 0.05). The differences in JOA scores and ODI scores between the two groups at 3 months, 1 year, and 3 years postoperatively were statistically significant (P < 0.05). CONCLUSION: The early clinical efficacy of MIS-TLIF was superior to that of TLIF, but no differences were found in mid-term clinical efficacy. Further, MIS-TLIF has the advantages of fewer medical injuries, shorter hospitalization times, and faster postoperative functional recovery.
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Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Procedimientos Quirúrgicos Mínimamente Invasivos , Complicaciones Posoperatorias , Fusión Vertebral , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Fusión Vertebral/métodos , Masculino , Femenino , Vértebras Lumbares/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Complicaciones Posoperatorias/etiología , Estudios de SeguimientoRESUMEN
Tendinopathy is a prevalent condition in orthopedics patients, exerting a profound impact on tendon functionality. However, its underlying mechanism remains elusive and the efficacy of pharmacological interventions continues to be suboptimal. Verapamil is a clinically used medicine with anti-inflammation and antioxidant functions. This investigation aimed to elucidate the impact of verapamil in tendinopathy and the underlying mechanisms through which verapamil ameliorates the severity of tendinopathy. In in vitro experiments, primary tenocytes were exposed to interleukin-1 beta (IL-1ß) along with verapamil at a concentration of 5 µM. In addition, an in vivo rat tendinopathy model was induced through the localized injection of collagenase into the Achilles tendons of rats, and verapamil was injected into these tendons at a concentration of 5 µM. The in vitro findings highlighted the remarkable ability of verapamil to attenuate extracellular matrix degradation and apoptosis triggered by inflammation in tenocytes stimulated by IL-1ß. Furthermore, verapamil was observed to significantly suppress the inflammation-related MAPK/NFκB pathway. Subsequent investigations revealed that verapamil exerts a remediating effect on mitochondrial dysfunction, which was achieved through activation of the Nrf2/HO-1 pathway. Nevertheless, the protective effect of verapamil was nullified with the utilization of the Nrf2 inhibitor ML385. In summary, the in vivo and in vitro results indicate that the administration of verapamil profoundly mitigates the severity of tendinopathy through suppression of inflammation and activation of the Nrf2/HO-1 pathway. These findings suggest that verapamil is a promising therapeutic agent for the treatment of tendinopathy, deserving further and expanded research.
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Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5ß1. FBN1-Integrin α5ß1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5ß1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.
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Soy sauce is a traditional fermented food produced from soybean and wheat under the action of microorganisms. The soy sauce brewing process mainly involves two steps, namely koji fermentation and moromi fermentation. In the koji fermentation process, enzymes from starter molds, such as protease, aminopeptidase, carboxypeptidase, l-glutaminase, amylase, and cellulase, hydrolyze the protein and starch in the raw ingredients to produce short-chain substances. However, the enzymatic reactions may be diminished after being subjected to moromi fermentation due to its high NaCl concentration. These enzymatically hydrolyzed products are further metabolized by lactic acid bacteria and yeasts during the moromi fermentation process into organic acids and aromatic compounds, giving soy sauce a unique flavor. Thus, the starter molds, such as Aspergillus oryzae, Aspergillus sojae, and Aspergillus niger, and their secreted enzymes play crucial roles in soy sauce brewing. This review comprehensively covers the characteristics of the starter molds mainly used in soy sauce brewing, the enzymes produced by starter molds, and the roles of enzymes in the degradation of raw material. We also enumerate current problems in the production of soy sauce, aiming to offer some directions for the improvement of soy sauce taste.