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Background: High-intensity chemotherapy can cause life-threatening complications in pediatric patients. Therefore, this study investigated safety and efficacy of long-acting pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF; Jinyouli®) in children undergoing high-intensity chemotherapy. Methods: Treatment-naive patients received post-chemotherapy PEG-rhG-CSF as primary prophylaxis for two cycles. The primary endpoints were drug-related adverse events (AEs) and bone pain scores. Secondary endpoints included grade 3-4 neutropenia, duration of neutropenia recovery, absolute neutrophil count changes, febrile neutropenia (FN), reduced chemotherapy intensity, antibiotic usage, and AE severity. The cost-effectiveness of PEG-rhG-CSF was compared with that of rhG-CSF (Ruibai®). Results: Here, 307 and 288 patients underwent one and two PEG-rhG-CSF cycles, respectively. Ninety-one patients experienced drug-related AEs, primarily bone pain (12.7%). Moreover, Grade 3-4 neutropenia and FN were observed. Median FN durations were 3.0 days in both cycles. No drug-related delays were observed during chemotherapy. One patient experienced grade 4 neutropenia-induced reduction in chemotherapy intensity during cycle 2. In total, 138 patients received antibiotics. PEG-rhG-CSF exhibited superior cost-effectiveness compared to rhG-CSF. Conclusion: Our findings indicate that PEG-rhG-CSF is safe, efficient, and cost-effective in pediatric patients undergoing high-intensity chemotherapy, providing preliminary evidence warranting further randomized controlled trials.
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The recovery of valuable metals from used lithium batteries is essential from an environmental and resource management standpoint. However, the most widely used acid leaching method causes significant ecological harm. Here, we proposed a method of recovering Li and Fe selectively from used lithium iron phosphate batteries by using low-concentration organic acid and completing the closed-loop regeneration. Low-concentration oxalic acid is used to carry out PO43-, which is significantly less soluble in aqueous solution than Li, two-stage selective leaching Li, where the leaching rate of Li reaches 99 %, and the leaching rate of Fe is only 2.4 %. The leach solution is then decontaminated. The solubility of Li3PO4 in aqueous solution is much smaller than that of Li2C2O4, which was required to recover Li to change the pH and Li can be recovered as Li3PO4; Fe can be retrieved as FeC2O4·2H2O, and re-prepared into lithium iron phosphate.
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Compuestos Férricos , Litio , Ácido Oxálico , Fosfatos , Reciclaje , Ácido Oxálico/química , Fosfatos/química , Litio/química , Reciclaje/métodos , Hierro/química , Suministros de Energía EléctricaRESUMEN
The sleep-breathing condition obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, which can exacerbate oxidative stress and free radical generation, thereby detrimentally impacting both motor and sensory nerve function and inducing muscular damage. OSA development is promoted by increasing proportions of fast-twitch muscle fibers in the genioglossus. Orientin, a water-soluble dietary C-glycosyl flavonoid with antioxidant properties, increased the expression of slow myosin heavy chain (MyHC) and signaling factors associated with AMP-activated protein kinase (AMPK) activation both in vivo and in vitro. Inhibiting AMPK signaling diminished the effects of orientin on slow MyHC, fast MyHC, and Sirt1 expression. Overall, orientin enhanced type I muscle fibers in the genioglossus, enhanced antioxidant capacity, increased mitochondrial biogenesis through AMPK signaling, and ultimately improved fatigue resistance in C2C12 myotubes and mouse genioglossus. These findings suggest that orientin may contribute to upper airway stability in patients with OSA, potentially preventing airway collapse.
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Proteínas Quinasas Activadas por AMP , Glucósidos , Apnea Obstructiva del Sueño , Humanos , Ratones , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Antioxidantes/metabolismo , Biogénesis de Organelos , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Flavonoides/metabolismo , Apnea Obstructiva del Sueño/metabolismoRESUMEN
Background and Objective: Neuroblastoma (NB) is a common malignant tumor in children, and its treatment remains challenging. Precision medicine, as an individualized treatment strategy, aims to improve efficacy and reduce toxicity by combining unique patient- and tumor-related factors, bringing new hope for NB treatment. In this article, we review the evidence related to precision medicine in NB, with a focus on potential clinically actionable targets and a series of targeted drugs associated with NB. Methods: We conducted an extensive search in PubMed, EMBASE, and Web of Science using key terms and database-specific strategies, filtered for time and language, to ensure a comprehensive collection of literature related to precision medicine in NB. The main search terms consisted of "neuroblastoma", "precision medicine", "pediatrics", and "targeting". The articles included in this study encompass those published from 1985 to the present, without restrictions on the type of articles. Key Content and Findings: ALK inhibitors and MYCN inhibitors have been developed to interfere with tumor cell growth and dissemination, thereby improving treatment outcomes. Additionally, systematic testing to identify relevant driver mutations is crucial and can be used for diagnosis and prognostic assessment through the detection of many associated molecular markers. Furthermore, liquid biopsy, a non-invasive tumor detection method, can complement tissue biopsy and play a role in NB by analyzing circulating tumor DNA and circulating tumor cells to provide genetic information and molecular characteristics of the tumor. Recently, trials conducted by many pediatric oncology groups have shown the urgent need for new approaches to cure relapsed and refractory patients. Conclusions: The purpose of this review is to summarize the latest advances in clinical treatment of NB, to better understand and focus on the development of promising treatment approaches, and to expedite the transition to the precision medicine clinical relevance in NB patients.
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BACKGROUND: Depression is closely linked to an imbalance in the autonomic nervous system (ANS). However, the role of this imbalance in mediating the effects of sleep deprivation (SD) and vagus nerve stimulation (VNS) on emotional well-being is not fully understood. METHODS: A population-based analysis was conducted to explore the relationship between sleep duration, depression scores, and heart rate variability (HRV). Additionally, the chronic SD mouse model was established to assess the impact of preventive transcutaneous auricular VNS (taVNS) on pathological and behavioral changes. RESULTS: Our study found a significant link between sleep duration, depression severity, and HRV. Shorter sleep duration was associated with higher depression scores and lower RMSSD (a measure of HRV). In our rat model, insufficient sleep consistently impaired HRV. This effect was mitigated by taVNS, accompanied by corresponding changes in levels of IL-1ß and IL-6, astrocyte and microglia activation, and tail suspension times. CONCLUSIONS: Using VNS as a preventive treatment for depression-risk individuals with insufficient sleep shows promise. It not only broadens the potential applications of VNS but also sheds light on its mechanism-particularly its role in enhancing vagal nerve function and balancing the ANS, as evidenced by HRV measurements.
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Privación de Sueño , Estimulación del Nervio Vago , Ratones , Ratas , Animales , Depresión/prevención & control , Sistema Nervioso Autónomo , Factores de TiempoRESUMEN
Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), may increase the risk of cancer development and a poor cancer prognosis. TAMs of the M2 phenotype, together with the intermittent hypoxic environment within the tumor, drive tumor aggressiveness. However, the mechanism of TAMs in IH remains unclear. In our study, IH induced the recruitment of macrophages, and IH-induced M2-like TAMs promoted glycolysis in laryngeal cancer cells through hexokinase 1. The hexokinase inhibitor 2-deoxy-D-glucose and HK1 shRNA were applied to verify this finding, confirming that M2-like TAMs enhanced glycolysis in laryngeal cancer cells through HK1 under intermittent hypoxic conditions. Comprehensive RNA-seq analysis disclosed a marked elevation in the expression levels of the transcription factor ZBTB10, while evaluation of a laryngeal cancer patient tissue microarray demonstrated a positive correlation between ZBTB10 and HK1 expression in laryngeal carcinoma. Knockdown of ZBTB10 decreased HK1 expression, and overexpression of ZBTB10 increased HK1 expression in both laryngeal cancer cells and 293T cells. The luciferase reporter assay and Chromatin immunoprecipitation assay confirmed that ZBTB10 directly bound to the promoter region of HK1 and regulated the transcriptional activity of HK1. Finally, the CLEC3B level of the M2 supernatant is significantly higher in the IH group and showed a protumor effect on Hep2 cells. As ZBTB10-mediated regulation of HK1 affects glycolysis in laryngeal cancer, our findings may provide new potential therapeutic targets for laryngeal cancer.
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Glucólisis , Hexoquinasa , Neoplasias Laríngeas , Proteínas Represoras , Apnea Obstructiva del Sueño , Humanos , Hexoquinasa/genética , Hexoquinasa/metabolismo , Hipoxia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Proteínas Represoras/metabolismo , ARN Interferente Pequeño/metabolismo , Apnea Obstructiva del Sueño/complicacionesRESUMEN
Purpose: Endometrial carcinoma (EC) is one of the three most common female genital tract cancers, and it contributes to the leading deaths of gynecologic cancer. MTHFD2 was reported up-regulated and associated with poor prognosis in many malignancies. However, its biological functions and mechanisms in EC are unclear. The present study aimed to identify the biological functions and potential molecular mechanisms of MTHFD2 in EC. Methods: The gene expression and information of patients used in this study were derived from TCGA, GEO and HPA databases. KM survival analysis was used to explore the clinical outcomes of EC patients and correlation analysis was applied to find the correction between MTHFD2 expression level and immune infiltration in EC. We used GO and GSEA analysis to explore the biological functions and mechanisms of MTHFD2. The CCK8 assay, the colony formation assay and the transwell migration assay were conducted to validate the function of MTHFD2 in EC cells. We applied STRING to find the protein that interacted with MTHFD2. Finally, ENCORI was used to explore the potential upstream regulation of MTHFD2 in EC and it was validated in EC cells. Results: In the present study, we found that MTHFD2 was up-regulated in EC and its high expression level was associated with patients' poor prognosis and adverse clinical parameters. MTHFD2 level was shown to be correlated with immune infiltration. Knockdown of MTHFD2 inhibited the malignant phenotype of HEC-1A and Ishikawa cells, including proliferation, colony formation and migration. Furthermore, we found the SNHG3/hsa-miR-455-5p axis as the potential upstream of MTHFD2. Conclusion: SNHG3/hsa-miR-455-5p axis-mediated high expression of MTHFD2, and the MTHFD2 expression level was associated with tumor immune infiltration and endometrial carcinoma progression. Knockdown of MTHFD2 significantly inhibited the malignant phenotype of EC cells. MTHFD2 may be a valuable predictive biomarker, and targeting MTHFD2 may be an effective way to improve the therapeutic effect in EC.
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Neoplasias Endometriales , MicroARNs , Femenino , Humanos , Línea Celular Tumoral , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
Both obesity and obstructive sleep apnea (OSA) can lead to metabolic dysregulation and systemic inflammation. Similar to obesity, increasing evidence has revealed that immune infiltration in the visceral adipose tissue (VAT) is associated with obstructive sleep apnea-related morbidity. However, the pathological changes and potential molecular mechanisms in visceral adipose tissue of obstructive sleep apnea patients need to be further studied. Herein, by bioinformatics analysis and clinical validation methods, including the immune-related differentially expressed genes (IRDEGs) analysis, protein-protein interaction network (PPI), functional enrichment analysis, a devolution algorithm (CIBERSORT), spearman's correlation analysis, polymerase chain reaction (PCR), Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), we identified and validated 10 hub IRDEGs, the relative mRNA expression of four hub genes (CRP, CD40LG, CCL20, and GZMB), and the protein expression level of two hub genes (CD40LG and GZMB) were consistent with the bioinformatics analysis results. Immune infiltration results further revealed that obstructive sleep apnea patients contained a higher proportion of pro-inflammatory M1 macrophages and a lower proportion of M2 macrophages. Spearman's correlation analysis showed that CD40LG was positively correlated with M1 macrophages and GZMB was negatively correlated with M2 macrophages. CD40LG and GZMB might play a vital role in the visceral adipose tissue homeostasis of obstructive sleep apnea patients. Their interaction with macrophages and involved pathways not only provides new insights for understanding molecular mechanisms but also be of great significance in discovering novel small molecules or other promising candidates as immunotherapies of OSA-associated metabolic complications.
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Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder. Half of these cases occur in children with neuroblastoma. Neuroblastoma patients with OMS usually have better oncological outcomes than those without OMS even after stratification by tumor stage and age, indicating that factors mediating OMS may also inhibit tumor cell proliferation. Although the mechanisms underlying OMS remain undefined, the cytokines and lymphocytes alterations in the cerebrospinal fluid support the concept that it is a pattern of neuroinflammation due to an autoimmune effect. The presence of lymphoid follicles consisting of follicular dendritic cells, CD20+ B lymphocytes, CD3+ T lymphocytes, and CD68+ macrophages in the tumor microenvironment in OMS-associated neuroblastoma support the autoimmune nature of this disorder. This review focuses on the clinical and genetic features of OMS-associated neuroblastoma, and we update readers on immune features of neuroblastoma with or without OMS to gain insights into antitumor immunity as it relates to tumor biology and prognosis.
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Neuroblastoma , Síndrome de Opsoclonía-Mioclonía , Niño , Citocinas , Humanos , Linfocitos , Neuroblastoma/patología , Pronóstico , Microambiente TumoralRESUMEN
PURPOSE: Hypoxia is a common feature of laryngocarcinoma. Alterations in lipid metabolism are an important metabolic rewiring phenomenon for malignant cells to maintain their rapid proliferation in the hypoxic microenvironment, which makes most cancers, including laryngocarcinoma, difficult to cure. However, the mechanisms involved in lipid metabolism in laryngocarcinoma is still unclear. This study aimed to clarify the changes in lipid metabolism of laryngocarcinoma cells under hypoxic conditions and explore the related mechanisms. METHODS: Hep2 cells were incubated in a normoxic or hypoxic environment (5% CO2 and 1% O2) at 37 °C for 24 h. CCK-8 cell viability assay and colony formation assay were performed to detect cells proliferation. And lipid metabolic indices including TG and NEFA were determined by kits. The mechanism involved in the regulation of lipid metabolism was explored by RNA-seq and bioinformatic analysis. The MIF inhibitor ISO-1 and JAK inhibitor XL019 were used to verify the mechanism. Finally, a tumour xenograft model was applied to further verify these results in vivo. RESULTS: Hypoxia promoted cell proliferation and increased the levels of TG and NEFA in Hep2 cells. Three genes, MIF, ENO2, and LDHA, that were screened by the intersection of hypoxia gene sets and fatty gene sets and were verified by qPCR. The MIF levels were elevated when cells were exposed to hypoxia. Through GSEA and RNA-seq analysis, the JAK/STAT pathway was screened. Hypoxia increased MIF levels and activated the IL-6/JAK/STAT pathway. The MIF inhibitor ISO-1inhibited cell proliferation under hypoxia and reversed the change in TG levels and IL-6 levels. And ISO-1 reversed the expression pattern of the screened genes in the JAK/STAT pathway. Finally, a tumour xenograft model further verified these results in vivo. CONCLUSION: Hypoxia induced reprogramming of lipid metabolism in laryngocarcinoma cells through the MIF/IL-6/JAK-STAT pathway. This study revealed one mechanism that allows laryngocarcinoma cells to adapt to the hypoxic tumour microenvironment. Therefore, a drug targeting the MIF/IL-6/JAK-STAT pathway might be a promising therapeutic option for the treatment of laryngocarcinoma.
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Quinasas Janus , Factores Inhibidores de la Migración de Macrófagos , Transducción de Señal , Animales , Hipoxia de la Célula , Línea Celular Tumoral , Ácidos Grasos no Esterificados , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Oxidorreductasas Intramoleculares , Quinasas Janus/genética , Metabolismo de los Lípidos/genética , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Factores de Transcripción STAT/genéticaRESUMEN
PURPOSE: Folate-mediated one-carbon metabolism (FOCM) plays a vital role in supporting cancer cells hyperproliferation. Malignant cells, including nasopharyngeal carcinoma (NPC) cells, are characterized by rapid proliferation and thus need large numbers of nucleotides and nutrients generated from FOCM. However, the mechanism and key genes involved in FOCM playing a vital role in NPC progression are still unclear. This study aimed to find out the key gene, and its functions in NPC and explore the potential mechanism. METHODS: Bioinformatics analysis based on TCGA and GSEA database were performed to screen the key FOCM related gene in HNSCC. The effects of MTHFD2 on cell proliferation, apoptosis and migration were conducted through MTHFD2 knockdown cell lines in vitro experiments. Cell proliferation was explored by CCK8 assay and colony formation assay. Cell apoptosis was tested through flow cytometry. Transwell migration assay was performed to study the cell migration. The potential pathway was explored by RNA-seq and the ERK inhibitor SCH772984 and the ERK activator tBHQ were applied to verify the effect of MTHFD2 in NPC via the ERK pathway. Finally, xenograft tumor model was used to explore the tumorigenicity of NPC cells in vivo and IHC was performed to study the expression of related proteins. RESULTS: MTHFD2 was highly expressed in NPC and associated with a poor prognosis. MTHFD2 knockdown inhibited the proliferation, migration and induced apoptosis of NPC cells in vitro. In consistent with cellular results, knockdown of MTHFD2 suppressed the tumorigenicity of NPC cells in vivo. MAPK pathway was enriched among DEGs between MTHFD2 knockdown cells and control cells. And the level of p-ERK1/2 and p-p38 MAPK was decreased in MTHFD2 knockdown cells and xenograft tumors of MTHFD2 knockdown cells. Furthermore, the application of the selective ERK inhibitor SCH772984 and the ERK activator tBHQ confirmed that MTHFD2-knockdown inhibited the proliferation and migration of NPC cells via the ERK signaling pathway. CONCLUSION: MTHFD2 was up-regulated in NPC tissues and its high expression was linked to a poor prognosis. Knockdown of MTHFD2 inhibited proliferation and migration of NPC cells through the ERK signaling pathway, which may provide new clues and targets for the treatment of NPC.
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Sistema de Señalización de MAP Quinasas , Neoplasias Nasofaríngeas , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Transducción de SeñalRESUMEN
INTRODUCTION: Dysregulation of iron metabolism is closely associated with the development of obesity and obstructive sleep apnea (OSA), but little is known about the relationship between serum transferrin (TF) level and OSA severity. We aimed to verify this relationship and fit into account for obesity-related confounders among bariatric candidates. METHODS: We compared data retrospectively collected in 270 bariatric candidates. A propensity score-matched (PSM) analysis was used to determine the impact of iron metabolism on OSA severity independently of obesity. Univariate analysis was used to evaluate the relationship between serum TF level and the severity of OSA reflected by hypoxia and night awakenings parameters. Serum TF level to predict the severity of OSA was assessed by using univariate and multiple logistic regression model. RESULTS: The preliminary analysis showed that serum ferritin (113 ng/mL [50-203] vs. 79 ng/mL [40-130], p = 0.009) and TF (2.72 g/L [2.46-3.09] vs. 2.65 g/L [2.34-2.93], p = 0.039) level was significantly higher in the moderate/severe OSA group than the no/mild OSA group. After PSM analysis, there were 75 patients in each group and only serum TF level remained significant (p = 0.014). The proportion of patients with combined T2D and hyperlipidemia also remained higher in moderate/severe OSA groups. Univariate analysis showed that the group with higher degree of hypoxia had higher serum TF levels no matter the severity of OSA was grouped by oxygen desaturation index (ODI; 2.79 g/L [2.56-3.06] vs. 2.55 g/L [2.22-2.84], p < 0.001) or minimum oxygen saturation (SpO2nadir; 2.75 g/L [2.50-3.03] vs. 2.56 g/L [2.24-2.92], p = 0.009). Univariate and multiple logistic regression analysis further showed that serum TF level emerged as a significant and independent factor associated with OSA severity especially grouped by ODI (odds ratio: 2.91, 95% CI: 1.36-6.23, p = 0.006). CONCLUSION: The existence of OSA exacerbates obesity comorbidities, particularly type 2 diabetes and hyperlipidemia. Serum TF level is associated with the severity of OSA independently of obesity and might be a potential identification and therapeutic targets.
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Diabetes Mellitus Tipo 2 , Apnea Obstructiva del Sueño , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hipoxia , Hierro , Obesidad/complicaciones , Puntaje de Propensión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , TransferrinasRESUMEN
Following the publication of the above article (and a Corrigendum that has already been published with the intention of showing the corrected version of Fig. 6 (DOI:10.3892/ijmm.2020.4786; published online on November 11, 2020), an interested reader drew to the authors' attention that, in Fig. 5B on p. 1233, the 'OA' and 'OA+IGF1+PNS' data panels appeared to show overlapping data. The authors have reexamined their original data, and realize that Fig. 5 was assembled incorrectly; essentially, the 'OA+IGF1+PNS' data panel for Fig. 5B was selected in error. The corrected version of Fig. 5 is shown on the next page. Note that this inadvertent error did not affect the main conclusions reported in this study. The authors are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published on International Journal of Molecular Medicine 45: 12251236, 2020; DOI: 10.3892/ijmm.2020.4491].
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Osteoarthritis (OA) is a degenerative disease characterized by matrix degradation and cell death leading to a gradual loss of articular cartilage integrity. As a bacterial synthesis of quinine, pyrroloquinoline quinone (PQQ) is a strong redox cofactor with a variety of biological benefits, including antioxidant, anti-inflammation-induced mitochondrial metabolism regulation. This study was designed to investigate the effect of PQQ on TNF-α-induced mitochondrial damage in chondrocytes. Chondrocytes isolated from C57BL/6 mice were exposed to TNF-α 50 ng/mL, TNF-α 50 ng/mL + PQQ 10 µmol/L for 24 h. Then, morphological study, functional study and mechanism study were taken. The results revealed TNF-α-induced chondrocyte mitochondrion damage could be reduced by application of PQQ, evidenced by elevated number of mitochondria, well-kept mtDNA integrity, preserved ATP level, reestablished mitochondrial membrane potential, and prevented mitochondrial function. The present work strongly suggests that the mitochondrion is an important target for OA chondrocyte damage induced by TNF-α and the PQQ protection from this damage ameliorates mitochondrial dysfunction induced by TNF-α. PQQ might be a potential chemical for OA intervention.
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Antiinflamatorios/farmacología , Condrocitos/efectos de los fármacos , Mitocondrias/metabolismo , Osteoartritis/metabolismo , Cofactor PQQ/farmacología , Adenosina Trifosfato/metabolismo , Animales , Células Cultivadas , Condrocitos/metabolismo , Daño del ADN , Potencial de la Membrana Mitocondrial , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: Even though many studies have proven the risk factors for cancer in children, studies focusing exclusively on second children are absent. This study is designed to examine the association between maternal exposure during pregnancy and the risk of developing solid tumors (STs) in second children. METHODS: This retrospective matched case-control study included 80 s children with STs and 160 s children without STs matched in terms of birth weight, gestational age, pregnancy body mass index (BMI), and residence from a medical center. Exposure during pregnancy and birth characteristics of these children were investigated through structured questionnaires. RESULTS: A univariate analysis suggested that birth spacing (OR, 12.70; CI, 4.44-36.34), maternal smoking (OR, 6.00; CI, 1.62-22.16), paternal smoking (OR, 2.20; CI, 1.23-3.93), and common cold (OR,1.94; CI, 1.02-3.69) were associated with an increased risk of second children STs. A multivariate analysis demonstrated that birth spacing (OR, 12.45; CI, 4.00-38.78) and paternal smoking (OR, 2.04; CI, 1.04-3.99) were the main risk factors for STs in second-born children. CONCLUSION: Long birth spacing (>10 years) and paternal smoking could significantly increase the risk of developing STs in second-born children. Despite the fact that the effects of maternal smoking and the common cold were not significant, it is still recommended to quit smoking, take necessary self-protective measures to reduce the risk of infection.
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Neoplasias , Efectos Tardíos de la Exposición Prenatal , Peso al Nacer , Estudios de Casos y Controles , Niño , China/epidemiología , Femenino , Humanos , Neoplasias/epidemiología , Neoplasias/etiología , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Following the publication of the above article, the authors have realized that the first author, who analyzed the data, inadvertently made a mistake by overestimating the background of the blots in calculating the intensity of the histograms for the western blots shown in Fig. 6A and E. This error led to subsequent differences in the actual quantification and statistics from the originally submitted results. Accordingly, to further verify the conclusions reported in the study, the authors repeated these experiments independently, and the results were found to be consistent with the same changes in trends as originally observed. The revised version of Fig. 6, containing the new western blot data for Fig. 6A and E and new histograms showing the quantification of these data, is shown on the next page. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 45: 1225-1236, 2020; DOI: 10.3892/ijmm.2020.4491].
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Colorectal cancer is a rare pediatric tumor. Pediatric patients with colorectal cancer present with more aggressive tumor biology and at later stages of the disease, higher proportions of signet ring and mucinous histology, and less differentiation. The effective treatment is same as that received by adults. The overall prognosis of pediatric colorectal cancer is generally poor. Genetic mutations have been identiï¬ed as the cause of inherited cancer risk in some colorectal cancers. Here, we presented a case of a pediatric patient carrying a maternally derived, heterozygous MYH germline mutation (c.934-2A>G,intron), the mutation was not reported in pediatric patients before. Also, the patient carried somatic mutations of proto-oncogene SMAD4 (R361C) and TP53 (Y234H). The patient underwent surgical resection, chemotherapy and targeted therapy, but the prognosis was not good. We also review the literature to summarize clinical features, gene mutations, management, and outcomes of pediatric colorectal cancer patient. Our results suggest that the genetic mutation of MYH together with somatic mutations of proto-oncogene SMAD4 and TP53 may lead to the early onset colorectal cancer of the patient. Although the overall prognosis of pediatric colorectal cancer is generally poor, the pathogenesis may be related to hereditary genetic mutations as was found with the MYH gene mutation in our case. Genetic screening can provide early diagnosis and improve prognosis.
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Hypoxia/reoxygenation (H/R) may play an important role via senescence in the mechanism of osteoarthritis (OA) development. The synovial membrane is highly sensitive to H/R due to its oxygen consumption feature. Excessive mechanical loads and oxidative stress caused by H/R induce a senescenceassociated secretory phenotype (SASP), which is related to the development of OA. The aim of the present study was to investigate the differences of SASP manifestation in synovial tissue masses between tissues from healthy controls and patients with OA. The present study used tumor necrosis factorα (TNFα) to pretreat synovial tissue and fibroblastlike synoviocytes (FLS) to observe the effect of inflammatory cytokines on the synovial membrane before H/R. It was determined that H/R increased interleukin (IL)1ß and IL6 expression levels in TNFαinduced cell culture supernatants, increased the proportion of SAßgal staining, and increased the expression levels of high mobility group box 1, caspase8, p16, p21, matrix metalloproteinase (MMP)3 and MMP13 in the synovium. Furthermore, H/R opened the mitochondrial permeability transition pore, caused the loss of mitochondrial membrane potential (ΔΨm) and increased the release of reactive oxygen species (ROS). Moreover, H/R caused the expansion of the mitochondrial matrix and rupture of the mitochondrial extracorporeal membrane, with a decrease in the number of cristae. In addition, H/R induced activation of the JNK signaling pathway in FLS to induce cell senescence. Thus, the present results indicated that H/R may cause inflammation and escalate synovial inflammation induced by TNFα, which may lead to the pathogenesis of OA by increasing changes in synovial SASP and activating the JNK signaling pathway. Therefore, further studies expanding on the understanding of the pathogenesis of H/R etiology in OA are required.
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Hipoxia/patología , Sistema de Señalización de MAP Quinasas , Osteoartritis de la Rodilla/patología , Oxígeno/metabolismo , Sinoviocitos/patología , Adulto , Anciano , Células Cultivadas , Senescencia Celular , Femenino , Humanos , Hipoxia/metabolismo , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/metabolismo , Estrés Oxidativo , Membrana Sinovial , Sinoviocitos/citología , Sinoviocitos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Panax notoginseng saponins (PNS) are active extracts obtained from the P. notoginseng plant. PNS exhibit various antiinflammatory, antioxidant and antiaging pharmacological properties in some cells. However, the effects of PNS on senescence and apoptosis in chondrocytes have not been studied to date. In the present study, whether PNS could limit tumor necrosis factor (TNF)αinduced senescence and apoptosis in chondrocytes and whether they could slow down cartilage degeneration in a surgeryinduced rat osteoarthritis (OA) model by regulating the phosphatidyl inositol 3 kinase (PI3K)protein kinase B (AKT)mammalian target of rapamycin (mTOR) signaling pathway was examined. A potential mechanism underlying these effects was further elucidated. The present in vitro experiments showed that PNS significantly inhibited senescence and apoptosis in OA chondrocytes and prevented a decrease in the mitochondrial membrane potential and excessive mitochondrial permeability. In addition, the expression levels of autophagyrelated proteins and the antiapoptotic protein Bcl2 were significantly increased in PNStreated OA chondrocytes, but the expression levels of Bax and caspase3 were decreased; these effects were concentrationdependent. TNFα significantly increased the expression of pPI3K/pAKT/pmTOR in OA chondrocytes, whereas PNS reduced PI3K, AKT and mTOR phosphorylation. The results of the in vivo experiments demonstrated that PNS significantly inhibited the PI3KAKTmTOR signaling pathway and collagen II degradation, as well as reduced matrix metalloproteinase (MMP)3 and MMP13 expression in chondrocytes in a rat OA model, thus attenuating cartilage destruction in OA. The results obtained in the rat model were consistent with the in vitro experimental results. Furthermore, histological analyses and ultrastructural observations confirmed these results. Taken together, the results of the present study demonstrated that PNS may protect osteoarthritic chondrocytes from senescence and apoptosis by inhibiting the PI3KAKT pathway, thus delaying the degradation of articular cartilage.
Asunto(s)
Apoptosis/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Condrocitos/metabolismo , Osteoartritis/metabolismo , Panax notoginseng/química , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Saponinas/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Condrocitos/patología , Modelos Animales de Enfermedad , Humanos , Masculino , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Ratas , Ratas Sprague-Dawley , Saponinas/químicaRESUMEN
BACKGROUND: Osteoarthritis (OA) is the most common chronic degenerative joint disease and is mainly characterized by cartilage degeneration, subcartilage bone hyperplasia, osteophyte formation and joint space stenosis. Recent studies showed that synovitis might also be an important pathological change of OA. However, the molecular mechanisms of synovitis in OA are still not well understood. OBJECTIVE: This study was designed to identify key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis. MATERIALS AND METHODS: The gene expression profiles of GSE12021, GSE55235 and GSE55457 were downloaded from the GEO database. The differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional enrichment analyses were performed. A protein-protein interaction network (PPI) was constructed, and module analysis was performed using STRING and Cytoscape. The CIBERSORT algorithm was used to analyze the immune infiltration of synovial tissue between OA and normal controls. RESULTS: A total of 106 differentially expressed genes, including 68 downregulated genes and 38 upregulated genes, were detected. The PPI network was assessed, and the most significant module containing 14 hub genes was identified. Gene Ontology analysis revealed that the hub genes were significantly enriched in immune cell chemotaxis and cytokine activity. KEGG pathway analysis showed that the hub genes were significantly enriched in the rheumatoid arthritis signaling pathway, IL-17 signaling pathway and cytokine-cytokine receptor interaction signaling pathway. The immune infiltration profiles varied significantly between osteoarthritis and normal controls. Compared with normal tissue, OA synovial tissue contained a higher proportion of memory B cells, naive CD4+ T cells, regulatory T cells, resting dendritic cells and resting mast cells, while naive CD4+ T cells, activated NK cells, activated mast cells and eosinophils contributed to a relatively lower portion (P > 0.05). Finally, the expression levels of 11 hub genes were confirmed by RT-PCR. CONCLUSION: The hub genes and the difference in immune infiltration in synovial tissue between osteoarthritis and normal controls might provide new insight for understanding OA development.