Alterations in HCN1 expression and distribution during epileptogenesis in rats.

Background: The hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN1) is predominantly located in key regions associated with epilepsy, such as the neocortex and hippocampus. Under normal physiological conditions, HCN1 plays a crucial role in the excitatory and inhibitory regulation of neuronal networks. In temporal lobe epilepsy, the expression of HCN1 is decreased in the hippocampi of both animal models and patients.

Identification of mIDH1 R132C/S280F Inhibitors from Natural Products by Integrated Molecular Docking, Pharmacophore Modeling and Molecular Dynamics Simulations.

Mutant isocitrate dehydrogenase 1 (mIDH1) is a common driving factor in acute myeloid leukemia (AML), with the R132 mutation accounting for a high proportion. The U.S.

Harnessing natural product polysaccharides against lung cancer and revisit its novel mechanism.

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world.

Scalp ripple rates for rapid epilepsy differentiation and seizure activity assessment: Applicability and influential factors.

Objective: We aim to determine whether automatically detected ripple rate (ADRR) of 10-min scalp electroencephalography (EEG) during slow-wave sleep can be a useful tool for rapid epilepsy differentiation and seizure activity assessment, and we analyze the clinical factors that may affect the scalp ripple rates.

Methods: We retrospectively included 336 patients who underwent long-term video-EEG with a sampling rate ≥1000 Hz, and three groups were established based on their final clinical diagnosis (non-epilepsy; non-active epilepsy [epilepsy being seizure-free for at least 1 year]; and active epilepsy [epilepsy with one or more seizures in the past year]). ADRRs between groups were compared and diagnostic thresholds set according to the maximum of Youden index with the receiver-operating characteristic curve.

Imbalance between the function of Na-K-2Cl and K-Cl impairs Cl homeostasis in human focal cortical dysplasia.

Objective: Altered expression patterns of Na-K-2Cl (NKCC1) and K-Cl (KCC2) co-transporters have been implicated in the pathogenesis of epilepsy. Here, we assessed the effects of imbalanced NKCC1 and KCC2 on γ-aminobutyric acidergic (GABAergic) neurotransmission in certain brain regions involved in human focal cortical dysplasia (FCD).

Materials And Methods: We sought to map a micro-macro neuronal network to better understand the epileptogenesis mechanism.

High-Frequency Oscillations and Epileptogenic Network.

Epilepsy is a network disease caused by aberrant neocortical large-scale connectivity spanning regions on the scale of several centimeters. High-frequency oscillations, characterized by the 80-600 Hz signals in electroencephalography, have been proven to be a promising biomarker of epilepsy that can be used in assessing the severity and susceptibility of epilepsy as well as the location of the epileptogenic zone. However, the presence of a high-frequency oscillation network remains a topic of debate as high-frequency oscillations have been previously thought to be incapable of propagation, and the relationship between high-frequency oscillations and the epileptogenic network has rarely been discussed.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

Objective: We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms.

Methods: Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period.

Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy.

Objective: Programmed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota.

Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening.

IDH1 mutations occur in about 20-30% of gliomas and are a promising target for the treatment of cancer. In the present study, the performance of aIDH1 was verified glide-docking-based virtual screening. On the basis of the two crystal structures (5TQH and 6B0Z) with the best discriminating ability to identify IDH1 inhibitors from a decoy set, a docking-based virtual screening strategy was employed for identifying new IDH1 inhibitors.

Evodiamine suppresses non-small cell lung cancer by elevating CD8 T cells and downregulating the MUC1-C/PD-L1 axis.

Background: Accumulating evidence showed that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Programmed Death Ligand 1 (PD-L1) is expressed in many cancer cell types, while its binding partner Programmed Death 1 (PD1) is expressed in activated T cells and antigen-presenting cells. Whereas, its dysregulation in the microenvironment is poorly understood.

Roles of Ion Fluxes, Metabolism, and Redox Balance in Cancer Therapy.

The 2019 Nobel Prize awarded to the mechanisms for oxygen sensing and adaptation according to oxygen availability, highlighting the fundamental importance of gaseous molecules. Gaseous molecules, including reactive oxygen species (ROS), can interact with different cations generated during metabolic and redox dysregulation in cancer cells. Cross talk between calcium signaling and metabolic/redox pathways leads to network-based dyregulation in cancer.

Dolutegravir derivative inhibits proliferation and induces apoptosis of non-small cell lung cancer cells via calcium signaling pathway.

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer. However, there has been little improvement in its cure rate in the last 30 years, due to its intricate heterogeneity and drug resistance. Accumulating evidences have demonstrated that dysregulation of calcium (Ca) homeostasis contributes to oncogenesis and promotes tumor development.

Prognostic significance of tumor poliovirus receptor and CTLA4 expression in patients with surgically resected non-small-cell lung cancer.

Introduction: Poliovirus receptor (PVR) is a tumor promoter and a regulatory checkpoint that enhances immunosuppression. We investigated PVR expression by applying immunohistochemistry (IHC) staining. A positive association existed between PVR expression and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expression in patients with surgically resected non-small-cell lung cancer (NSCLC).

MicroRNA-421 confers paclitaxel resistance by binding to the KEAP1 3'UTR and predicts poor survival in non-small cell lung cancer.

MicroRNAs regulate post-transcriptional gene expression and play important roles in multiple cellular processes. In this study, we found that miR-421 suppresses kelch-like ECH-associated protein 1(KEAP1) expression by targeting its 3'-untranslated region (3'UTR). A Q-PCR assay demonstrated that miR-421 is overexpressed in non-small cell lung cancer (NSCLC), especially in A549 cells.

Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer.

Background: The incidence of non-small cell lung cancer (NSCLC) accounts for approximately 85-90% of lung cancer, which has been shown to be challenging for treatment owing to poorly understanding of pathological mechanisms. Natural products serve as a source of almost all pharmaceutical preparations or offer guidance for those chemicals that have entered clinical trials, especially in NSCLC.

Purpose: We investigated the effect of B10G5, a natural products isolated from the Croton tiglium, in human non-small cell lung canceras as a protein kinase C (PKC) activator.

Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase.

Background: This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase.

Methods: Male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4 weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4 weeks.

Krukovine Suppresses KRAS-Mutated Lung Cancer Cell Growth and Proliferation by Inhibiting the RAF-ERK Pathway and Inactivating AKT Pathway.

Oncogenic activation of the KRAS gene via point mutations occurs in 20-30% of patients with non-small cell lung cancer (NSCLC). The RAS-RAF-ERK and RAS-PI3K-AKT pathways are the major hyper-activated downstream pathways in RAS mutation, which promotes the unlimited lifecycle of cancer cells and their metastasis in humans. However, the success of targeted therapy is restricted by many factors.

Gossypol Inhibits Non-small Cell Lung Cancer Cells Proliferation by Targeting EGFR.

Overexpression of epidermal growth factor receptor (EGFR) has been reported to be implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Several EGFR inhibitors have been used in clinical treatment of NSCLC, but the emergence of EGFR resistant mutation has reduced the efficacy of the clinical used EGFR inhibitors. There is an urgent need to develop novel EGFR inhibitors for better NSCLC treatment.

Effect of SQW on the bladder function of mice lacking TRPV1.

Background: Suo Quan Wan (SQW) is an effective traditional Chinese prescription on treated lower urinary tract symptoms (LUTS), and has been proved have modulation effect on the expression of transient receptor potential vanilloid 1 (TRPV1) in accordance with the recovery of bladder function of overactive bladder rat. This study further investigated the mechanism of SQW modulated TRPV1 signaling and bladder function using TRPV1 knockout (KO) mice.

Methods: Study was conducted using wild type and TRPV1 KO mice.

Effect of the Chinese traditional prescription Suo Quan Wan on TRPV1 expression in the bladder of rats with bladder outlet obstruction.

Background: Suo Quan Wan (SQW) is a Chinese traditional prescription that has been used in clinical treatment of lower urinary tract symptoms for centuries. However, scientific basis of SQW efficacy and mechanism is still needed. This study investigated the effect of SQW on bladder function and transient receptor potential vanilloid 1 (TRPV1) expression in the bladder of rats with bladder outlet obstruction (BOO).