RESUMEN
BACKGROUND: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells. METHODS: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation. RESULTS: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions. CONCLUSIONS: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.
Asunto(s)
Neoplasias Óseas , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Osteosarcoma , Humanos , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Metástasis de la Neoplasia , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/metabolismoRESUMEN
Amifostine is a normal cell protection agent, not only used in the adjuvant therapy of lung cancer, ovarian cancer, breast cancer, nasopharyngeal cancer, bone tumor, digestive tract tumor, blood system tumor and other cancers in order to reduce the toxicity of chemotherapy drugs, and recent studies have reported that the drug can also reduce lung tissue damage in patients with pulmonary fibrosis, but its mechanism of action is not yet fully understood. In this study, we explored the potential therapeutic effects and molecular mechanisms of AMI on bleomycin (BLM)-induced pulmonary fibrosis in mice. A mouse model of pulmonary fibrosis was established using BLM. We then assessed histopathological changes, inflammatory factors, oxidative indicators, apoptosis, epithelial-mesenchymal transition, extracellular matrix changes, and levels of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway-related proteins in the BLM-treated mice to determine the effect of AMI treatment on these factors. BLM-treated mice had substantial lung inflammation and abnormal extracellular matrix deposition. Overall, treatment with AMI significantly improved BLM-induced lung injury and pulmonary fibrosis. More specifically, AMI alleviated BLM-induced oxidative stress, inflammation, alveolar cell apoptosis, epithelial-mesenchymal transition, and extracellular matrix deposition by regulating the PI3K/Akt/mTOR signaling pathway. This finding that AMI can alleviate pulmonary fibrosis in a mouse model by inhibiting activation of the PI3K/Akt/mTOR signaling pathway lays a foundation for potential future clinical application of this agent in patients with pulmonary fibrosis.
Asunto(s)
Amifostina , Neoplasias Nasofaríngeas , Fibrosis Pulmonar , Animales , Ratones , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Bleomicina/toxicidad , Modelos Animales de Enfermedad , Transducción de Señal , Serina-Treonina Quinasas TOR , MamíferosRESUMEN
INTRODUCTION: Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature. PATIENT CONCERNS AND DIAGNOSIS: We report a 38-year-old woman with Ph-positive MDS. INTERVENTIONS AND OUTCOMES: She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed. CONCLUSION: Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Humanos , Femenino , Adulto , Cromosoma Filadelfia , Trasplante Homólogo , Enfermedades Raras , Síndromes Mielodisplásicos/terapiaRESUMEN
Mycoplasma pneumoniae is a common pathogen causing respiratory disease in children. We sought to investigate the epidemiology of M. pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the coronavirus disease 2019 (COVID-19) pandemic. Eligible patients were prospectively enrolled from January 2020 to June 2021. Throat swabs were tested for M. pneumoniae RNA. M. pneumoniae IgM was tested by a colloidal gold assay. Macrolide resistance and the effect of the COVID-19 countermeasures on M. pneumoniae prevalence were assessed. Symptom scores, treatments, and outcomes were evaluated. Eight hundred sixty-two eligible children at 15 centers in China were enrolled. M. pneumoniae was detected in 78 (9.0%) patients. Seasonally, M. pneumoniae peaked in the first spring and dropped dramatically to extremely low levels over time until the next summer. Decreases in COVID-19 prevalence were significantly associated with decreases in M. pneumoniae prevalence (r = 0.76, P = 0.001). The macrolide resistance rate was 7.7%. The overall sensitivity and specificity of the colloidal gold assay used in determining M. pneumoniae infection were 32.1% and 77.9%, respectively. No more benefits for improving the severity of symptoms and outcomes were observed in M. pneumoniae-infected patients treated with a macrolide than in those not treated with a macrolide during follow-up. The prevalences of M. pneumoniae and macrolide resistance in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs. IMPORTANCE This is the first and largest prospective, multicenter, active, population-based surveillance study of the epidemiology of Mycoplasma pneumoniae among outpatient children with mild respiratory tract infections (RTIs) during the COVID-19 pandemic. Nationwide measures like strict face mask wearing and restrictions on population movement implemented to prevent the spread of COVID-19 might also effectively prevent the spread of M. pneumoniae. The prevalence of M. pneumoniae and the proportion of drug-resistant M. pneumoniae isolates in outpatient children with mild RTIs were at low levels in the early stage of the COVID-19 pandemic but may have rebounded recently. The colloidal gold assay for M. pneumoniae IgM may be not appropriate for screening and diagnosis of M. pneumoniae infection. Macrolides should be used with caution among outpatients with mild RTIs.
Asunto(s)
Mycoplasma pneumoniae/aislamiento & purificación , Neumonía por Mycoplasma/microbiología , Infecciones del Sistema Respiratorio/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , COVID-19/epidemiología , Niño , Preescolar , China/epidemiología , Farmacorresistencia Bacteriana , Femenino , Humanos , Lactante , Macrólidos/uso terapéutico , Masculino , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/fisiología , Pacientes Ambulatorios/estadística & datos numéricos , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/epidemiología , Estudios Prospectivos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Acute appendicitis is one of the most common emergency requiring operation. As the first discovered coagulation factor, plasma fibrinogen frequently increases with inflammation due to the activation of coagulation. The aim of this retrospective study was to investigate the diagnostic value of hyperfibrinogenemia as a preoperative laboratory marker for appendiceal perforation in patients with acute appendicitis. MATERIALS AND METHODS: We identified 455 patients (202 females, 253 males; mean age, 31.7 years) with histologically confirmed acute appendicitis who underwent laparoscopic or open appendectomy. Results of preoperative laboratory values and post-operative histologic results were analysed retrospectively. A multivariate logistic regression model was performed to determine patient's age and laboratory tests associated with perforated appendicitis. RESULT: Mean plasma fibrinogen level of all patients was 3.99 g/L (1.41 SD; range, 1.73-10.6 g/L; median, 3.69 g/L). Patients with appendiceal perforation had a mean fibrinogen level of 5.72 g/L (1.52 SD; range, 3.38-10.04 g/L; median, 5.28 g/L), which was significantly higher than those with nonperforated groups (P = 0.001). Multivariate analysis showed fibrinogen and D-dimer were associated with perforation (P = 0.001, P = 0.014, respectively). Areas under the receiver operating characteristic curve of fibrinogen for discriminating acute perforated appendicitis from non-perforated groups were larger than white blood cell and D-dimer. CONCLUSIONS: Hyperfibrinogenemia was common in patients with acute appendicitis and fibrinogen may be useful as a predictive factor for appendiceal perforation.
Asunto(s)
Apendicitis/sangre , Apendicitis/cirugía , Fibrinógeno/análisis , Perforación Intestinal/sangre , Perforación Intestinal/diagnóstico , Enfermedad Aguda , Adulto , Apendicectomía/métodos , Apendicitis/complicaciones , Biomarcadores/sangre , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Inflamación/sangre , Inflamación/metabolismo , Perforación Intestinal/complicaciones , Laparoscopía/métodos , Recuento de Leucocitos/métodos , Masculino , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
BACKGROUND: RNA-binding protein LIN28 is involved in maintaining the pluripotency of embryonic stem cells. It has been detected in different types of testicular and ovarian germ cell tumors (GCTs), but its status in pediatric YSTs (yolk sac tumors) is still unknown. The aim of this study was to determine the immunohistochemical profile of LIN28 in pediatric YSTs. METHODS AND RESULTS: Immunohistochemistry detection of LIN28 was performed in 22 cases of pediatric YSTs and 10 mature teratomas. The percentage of tumor cells stained was scored as 0, 1+ (1-30 % cells), 2+ (31-60 %), 3+ (61-90 %), and 4+ (>90 %). To compare its sensitive and specificity with alpha-fetoprotein (AFP), we also stained AFP in 22 cases of pediatric YSTs and 10 mature teratomas in children. LIN28 staining was high in all 22 pediatric yolk sac tumor (2+ in 1, 3+ in 1, and 4+ in 20), and weak staining of LIN28 was seen in 1 of 10 mature teratomas (1+), 9 of 10 mature teratomas were negative expression. However, the expression of AFP in pediatric YST was lower compared with Lin28 (- in 1, 1+ in 8, 2+ in 12, and 3+ in 1), and weak expression of AFP was seen in 2 of 10 mature teratomas (1+), 8 of 10 mature teratomas were negative. LIN28 had higher intensity expression than AFP in pediatric YSTs (P < 0.001). CONCLUSIONS: LIN28 is a sensitive marker for pediatric YSTs and it can be used to distinguish them from mature teratomas. LIN28 is likely to become a new and valuable biomarker for diagnosing of pediatric YST.
Asunto(s)
Tumor del Seno Endodérmico/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas de Unión al ARN/metabolismo , Neoplasias Testiculares/metabolismo , Biomarcadores de Tumor/metabolismo , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Teratoma/metabolismo , alfa-Fetoproteínas/metabolismoRESUMEN
PURPOSE: Intussusception is one of the most common causes of acute abdominal emergencies in infants and preschool children. Loss of intestine viability is the most serious complication of intussusception. This study aimed to investigate the risk factors for loss of intestine viability in pediatric intussusception cases among children. METHODS: Data were collected for operative pediatric intussusception cases (N = 316) from medical records of 5,537 hospitalized children due to intussusception between June 2009 and May 2014 in a pediatric surgery department of an academic teaching hospital in China. Seventy-six patients (24.1 %) of the operated intussusception cases had complication of loss intestine viability. RESULTS: Pediatric intussusception cases with loss of intestine viability and without loss of intestine viability were similar in terms of their age, malformation and season of admission. The median time of the duration from onset of symptoms to operative treatment was 23 h (range 3-90 h). The loss of intestine viability group of the intussusception cases was significantly associated with longer length of history (P = 0.000). Receiver operating characteristic curve analysis for length of history showed that the optimal ratio of sensitivity (0.70) and specificity (0.73) was calculated for the length of history longer than 27.5 h regarding loss of intestine viability of intussusception. In addition, the risk of loss of intestine viability was higher for female (31 %) than for male (20.8 %) (P = 0.049). The loss of intestine viability rate was also significantly higher in ileo-ileal intussusception cases than that of the other types (P = 0.033). However, there is no difference among the other groups. CONCLUSION: The result of our risk factor analysis for loss of intestine viability in pediatric intussusception cases may help develop a predictability index to prevent the complication to happen. Further prospective studies are required to confirm our findings.