RESUMEN

Neuron apoptosis is a feature of secondary injury after traumatic brain injury (TBI). Evidence implies that excess calcium (Ca2+) ions and reactive oxidative species (ROS) play critical roles in apoptosis. In reaction to increased ROS, the anti-oxidative master transcription factor, Transient receptor potential Ankyrin 1 (TRPA1) allows Ca2+ ions to enter cells. However, the effect of TBI on the expression of TRPA1 and the role of TRPA1 in TBI are unclear. In the present study, TBI in the mouse brain was simulated using the weight-drop model. The process of neuronal oxidative stress was simulated in HT22 neuronal cells by treatment with hydrogen peroxide. We found that TRPA1 was significantly upregulated in neurons at 24 h after TBI. Neuronal apoptosis was increased in the in vivo and in vitro models; however, this increase was reduced by the functional inhibition of TRPA1 in both models. After TBI, TRPA1 was upregulated via nuclear factor, erythroid 2 like 2 (Nrf2) in neurons. TRPA1-mediated neuronal apoptosis after TBI might be achieved in part through the CaMKII/AKT/ERK signaling pathway. To sum up, TBI-triggered TRPA1 upregulation in neurons is mediated by Nrf2 and the functional blockade of TRPA1 attenuates neuronal apoptosis and improves neuronal dysfunction, partially mediated through the activation of the calcium/calmodulin dependent protein kinase II (CaMKII) extracellular regulated kinase (ERK)/protein kinase B (AKT) signaling pathway. Our results suggest that functional blockade of TRPA1 might be a promising therapeutic intervention related to ROS and Nrf2 in TBI.

Asunto(s)

RESUMEN

OBJECTIVE: Solitary fibrous tumors (SFTs) and haemangiopericytomas (HPCs) are rare mesenchymal tumors in central nervous system (CNS). Although progressed recognition to the diagnosis and treatment of SFT/HPCs, it still remains many confusions regarding on its occurrence, aggressive evolution, malignant transformation, dedifferentiation phenomenon, distant metastasis and unpredictable propensity. PATIENTS AND METHODS: Seventeen cases of CNS SFT/HPCs who underwent surgical treatment from January 2010 to December 2020 were collected in the authors' institute. Clinical, radiological, pathological data and followup details were reviewed in all cases. RESULTS: The age of this series was 41-73 years old. Seven cases located subtentorially, five cases originated from middle skull base and four in supratentorial. MRI shows iso-signal intensity on T1WI, and heterogeneous slightly long/short signal on T2WI. There is significant contrast after gadolinium-enhancement. It is easy to be misdiagnosed before surgery. The positive rate of nuclear STAT6 is 94.12%, higher than CD34 (87.5%). Eight patients were grade I, eight grade II and one in grade III. Five cases developed tumor relapse, in which two cases had local intracranial recurrence combined with dissemination and metastasis of cerebrospinal fluid in the spinal canal, accompanied by pathological malignant transformation, and another one occurred blood metastasis. CONCLUSIONS: CNS SFT/HPCs are rare intracranial tumors with unpredictable propensity. Gross total resection is critical to its overall clinical prognosis. Given its potential recurrence and malignant transition, adjuvant radiotherapies are recommended when necessary, and long-term follow-up is indispensable. The underlying molecular biological mechanisms are still needed to be further exploration.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate the safety profiles of Motherwort injection (MI). METHODS: A multi-center, prospective and drug- derived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications. This study was based on a very large population after the injection was approved and marketed in China. All patients using the injection in participating hospitals were monitored to determine the incidence, pattern, severity and outcome of associated adverse events. RESULTS: The post-marketing surveillance was performed in 10 094 female patients from April to December, 2015. The incidence of adverse drug reactions (ADRs) was 0.79¡ë(8/10 094). Among the 8 patients, the reported adverse events mainly included systemic abnormalities, such as fever, chills and eyelid edema; skin and appendages disorders, such as pruritus and rash; gastrointestinal disorders, such as nausea, abdominal distension and pain; heart rate and rhythm disorders, such as palpitation and increased heart rate. All of these ADRs were mild in severity. CONCLUSION: In this study the ADRs incidence rate of MI is very low, which supports that it is generally safe for use in obstetric and gynecological diseases. However, the total number of 8 ADRs recorded over a relatively short time span seems limited, and the low number of reports could not represent an absolute guarantee of safety.