Elevated Astrocytic NFAT5 of the hippocampus increases epilepsy susceptibility in hypoxic-ischemic mice.

Objective: Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal mortality, resulting in brain injury and persistent seizures that can last into the late neonatal period and beyond. Effective treatments and interventions for infants affected by hypoxia-ischemia remain lacking. Clinical investigations have indicated an elevation of nuclear factor of activated T cells 5 (NFAT5) in whole blood from umbilical cords of severely affected HIBD infants with epilepsy.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

Background: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain.

Neurotoxic A1 astrocytes promote neuronal ferroptosis via CXCL10/CXCR3 axis in epilepsy.

Epilepsy is a common neurological disorder with a complex etiology. Ferroptosis, a new form of programmed cell death, is characterized by the accumulation of lipid peroxides and associated with seizures. However, the underlying mechanism of ferroptosis in epilepsy remains elusive.

Blockade of Kv1.3 Potassium Channel Inhibits Microglia-Mediated Neuroinflammation in Epilepsy.

Epilepsy is a chronic neurological disorder whose pathophysiology relates to inflammation. The potassium channel Kv1.3 in microglia has been reported as a promising therapeutic target in neurological diseases in which neuroinflammation is involved, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and middle cerebral artery occlusion/reperfusion (MCAO/R).

Transient Receptor Potential Vanilloid 4: a Double-Edged Sword in the Central Nervous System.

Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel that can be activated by diverse stimuli, such as heat, mechanical force, hypo-osmolarity, and arachidonic acid metabolites. TRPV4 is widely expressed in the central nervous system (CNS) and participates in many significant physiological processes. However, accumulative evidence has suggested that deficiency, abnormal expression or distribution, and overactivation of TRPV4 are involved in pathological processes of multiple neurological diseases.

Two new dihydro--agarofuran sesquiterpenes from the roots of .

Two new dihydro--agarofuran sesquiterpenes chiapen T () and chiapen U (), along with chiapen A (), 1-hydroxy-2,6,12-triacetoxy-8-(-nicotinoyloxy)-9-(benzoyloxy)--dihydroagarofuran (), wilforlide B (), 3-hydroxy-2-oxo-3-friedelen-29-oic acid (), epikatonic acid (), 22-epi-maytenfolic acid (), maytenoic acid (), wilforic acid F (), wilforic acid B (), were reported for the first time from the . The structures of all the compounds were elucidated by HR-ESI-MS, 1 D and 2 D NMR spectra, as well as single-crystal X-ray diffraction analyses. Compounds and were examined for anti-inflammatory activity, respectively.

Distinct mechanisms underlying therapeutic potentials of CD20 in neurological and neuromuscular disease.

Cluster of differentiation 20 (CD20) is an integral membrane protein expressed mainly on different developmental stages of B lymphocytes and rarely on T lymphocytes, and it functions as a link to B cell antigen receptor (BCR) and immune microenvironment via regulating calcium ion influx, cell cycle progression and interaction between isotypic BCRs and their co-receptors. Diverse therapeutic monoclonal antibodies (mAbs) targeting CD20 are generated and grouped into two types based on the ability to redistribute CD20 into lipid rafts, which results in huge differences in response. Currently, multiple anti-CD20 mAbs have been approved as drugs for neurological and neuromuscular diseases with promising clinical efficacy.

Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4) Mitigates Seizures.

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism.

TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood.

Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1.

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy.

The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy.

Background: Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown.

Silencing of circIgf1r plays a protective role in neuronal injury via regulating astrocyte polarization during epilepsy.

Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis.

NFAT5 and HIF-1α Coordinate to Regulate NKCC1 Expression in Hippocampal Neurons After Hypoxia-Ischemia.

Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with severe long-term sequelae such as cerebral palsy, epilepsy and cognitive disabilities. Na-K-2Cl cotransporters 1 (NKCC1) is dramatically upregulated after hypoxia-ischemia (HI), which aggravates brain edema and brain damage. Clinically, an NKCC1-specific inhibitor, bumetanide, is used to treat diseases related to aberrant NKCC1 expression, but the underlying mechanism of aberrant NKCC1 expression has rarely been studied in HIE.

TRPV1 translocated to astrocytic membrane to promote migration and inflammatory infiltration thus promotes epilepsy after hypoxic ischemia in immature brain.

Background: Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy.

Hydrogen peroxide is a critical regulator of the hypoxia-induced alterations of store-operated Ca entry into rat pulmonary arterial smooth muscle cells.

To investigate the association between store-operated Ca entry (SOCE) and reactive oxygen species (ROS) during hypoxia, this study determined the changes of transient receptor potential canonical 1 (TRPC1) and Orai1, two candidate proteins for store-operated Ca (SOC) channels and their gate regulator, stromal interaction molecule 1 (STIM1), in a hypoxic environment and their relationship with ROS in pulmonary arterial smooth muscle cells (PASMCs). Exposure to hypoxia caused a transient Ca spike and subsequent Ca plateau of SOCE to be intensified in PASMCs when TRPC1, STIM1, and Orai1 were upregulated. SOCE in cells transfected with specific short hairpin RNA (shRNA) constructs was almost completely eliminated by the knockdown of TRPC1, STIM1, or Orai1 alone and was no longer affected by hypoxia exposure.

Mitochondria depletion abolishes agonist-induced Ca2+ plateau in airway smooth muscle cells: potential role of H2O2.

The mechanisms by which mitochondria regulate the sustained phase of agonist-induced responses in cytosolic Ca(2+) concentration as an independent organelle in whole is not clear. By exposing to ethidium bromide and supplying pyruvate and uridine, we established mitochondrial DNA (mtDNA)-depleted rat airway smooth muscle cells (RASMCs) with maintained cellular energy. Upon an exposure to 2 microM histamine, [Ca(2+)](i) in control RASMCs increased to a peak followed by a plateau above baseline, whereas [Ca(2+)](i) in mtDNA-depleted RASMCs jumped to a peak and then declined to baseline without any plateau.

Ca2+ oscillation frequency regulates agonist-stimulated gene expression in vascular endothelial cells.

A physiological membrane-receptor agonist typically stimulates oscillations, of varying frequencies, in cytosolic Ca2+ concentration ([Ca2+]i). Whether and how [Ca2+]i oscillation frequency regulates agonist-stimulated downstream events, such as gene expression, in non-excitable cells remain unknown. By precisely manipulating [Ca2+]i oscillation frequency in histamine-stimulated vascular endothelial cells (ECs), we demonstrate that the gene expression of vascular cell adhesion molecule 1 (VCAM1) critically depends on [Ca2+]i oscillation frequency in the presence, as well as the absence, of histamine stimulation.

[Relationships among expressions of hTERT, MDR1, MRP mRNA, and C-myc protein in non-small cell lung cancer].

Background & Objective: The latest researches showed that myc protein could up-regulate the expression of human telomerase reverse transcriptase (hTERT), multidrug resistance gene 1(MDR1), multidrug resistance-related protein (MRP) in some kinds of tumors, and hTERT is correlated with efficiency of anti-tumor chemotherapy. This study was to investigate relations among expressions of hTERT, MDR1, MRP mRNA, and C-myc protein in non-small cell lung cancer (NSCLC).

Methods: Expressions of hTERT, MDR1, MRP mRNA in 113 cases of NSCLC tissues were detected by in situ hybridization, expression of C-myc protein was detected by SP immunohistochemistry, their correlations with clinicopathologic features of NSCLC were statistically analyzed.

[Expression and significance of telomerase reverse transcriptase and its regulators in non-small cell lung carcinoma].

Background & Objective: Telomerase is a ribonucleoprotein complex, which is silent in normal human somatic cells but may be reactivated by a series of regulators, and cause tumorigenesis. As a critical factor of telomerase activity, much progression has been achieved in the study of regulation of human telomerase reverse transcriptase, but the detail mechanism is still not clear. This study was designed to investigate the relationship of expression of human telomerase reverse transcriptase mRNA (hTERT mRNA) and its regulators including c-myc, mutant p53, protein kinase C alpha (PKCalpha) with clinicopathological significance of expression of the four markers in non-small cell lung carcinoma (NSCLC).