Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research.

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy.

Elevated STMN1 Expression Correlates with Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

STMN1 is a cytosolic phosphoprotein that not only participates in cell division, but also plays an important role in other microtubule-dependent processes, such as cell motility. Furthermore, STMN1 acts as a "relay protein" in several intracellular signaling pathways that influence cell growth and differentiation. Thus, STMN1 is likely to support cellular processes essential for tumor progression: survival and migration. Indeed, elevated STMN1 expression has been reported in various types of human malignancies and is correlated with poor prognosis in these human malignancies. However, the clinical and prognostic significance of STMN1 in pancreatic ductal adenocarcinoma (PDAC) remains unknown. Thus, we assessed STMN1 in PDAC in this retrospective study. We first examined STMN1 expression in PDAC tissues from 27 cases and matched adjacent non-cancerous tissues by quantitative polymerase chain reaction (PCR) and western blot analyses. Next, immunohistochemistry was used to evaluate STMN1 expression in 87 archived paraffin-embedded PDAC specimens. STMN1 mRNA and protein expression levels were to a large extent up-regulated in PDAC tissue compared with their adjacent non-cancerous tissues. Moreover, STMN1 expression was closely correlated with histological differentiation, lymphatic metastasis, and TNM stage (P = 0.023, 0.047, and 0.014, respectively). In addition, PDAC patients with higher STMN1 expression died sooner than those with lower STMN1 expression (P < 0.01). Multivariate analysis demonstrated that STMN1 expression was an independent prognostic factor for PDAC patients (P < 0.01). Herein, we provide the first evidence that up-regulated STMN1 may contribute to tumor progression and poor prognosis in PDAC patients and may serve as a novel prognostic marker.

miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer.

Pancreatic cancer has the poorest prognosis among all cancer types, due to its late diagnosis and the lack of effective therapies. Therefore, identification of novel gene targets, which are differentially expressed in pancreatic cancer and functionally involved in the malignant phenotype, is critical to achieve early diagnosis and develop effective therapeutic strategies. microRNAs (miRNAs) are small non-coding RNAs, which negatively regulate the expression of their targets. Due to their various targets, miRNAs play a key role in a number of physiological processes and in oncogenesis. Therefore, investigating the role of miRNAs in tumor may contribute to the development of new diagnostic and therapeutic tools for various types of cancer, including pancreatic cancer. Here, we investigated the role of miR-193b in pancreatic cancer. Our data showed that the expression of miR-193b is markedly decreased in pancreatic cancer tissues compared to adjacent healthy tissues. The Panc-1 cell line transfected with the miR­193b exhibited significantly decreased proliferative, migratory, and invasive ability compared to untransfected cells. Moreover, miR-193b inhibited the expression of stathmin 1 (STMN1) and urokinase-type plasminogen activator (uPA) in Panc-1 cells. These data suggest that miR-193b acts as a tumor suppressor in pancreatic cancer. Therefore, miR-193b may constitute a promising therapeutic agent for the suppression of pancreatic cancer cell growth and metastasis.