Biophysical mechanisms underlying tefluthrin-induced modulation of gating changes and resurgent current generation in the human Na1.4 channel.

Human skeletal muscle contraction is triggered by activation of Na1.4 channels. Na1.

Targeting GPER1 to suppress autophagy as a male-specific therapeutic strategy for iron-induced striatal injury.

The functional outcome of intracerebral hemorrhage (ICH) in young male patients are poor than in premenopausal women. After ICH, ferrous iron accumulation causes a higher level of oxidative injury associated with autophagic cell death in striatum of male mice than in females. In rodent model of ferrous citrate (FC)-infusion that simulates iron accumulation after ICH, female endogenous estradiol (E) suppresses autophagy via estrogen receptor α (ERα) and contributes to less injury severity.

Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism.

Background: Nasal polyposis is characterised by persistent inflammation of the upper airways. Autophagy has been implicated in many chronic inflammatory diseases. Whether autophagy plays a role in nasal polyp (NP) inflammation is completely unknown and deserves investigation.

Autophagy is deficient in nasal polyps: implications for the pathogenesis of the disease.

Background: Nasal polyposis is characterized by persistent inflammation but the pathogenesis is complex and still debatable. Autophagy has been associated with many human health problems including chronic inflammatory airway diseases. Whether autophagy plays a role in nasal polyps and could be a therapeutic target is completely unknown.

Early inactivation of PKCε associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat.

Background: Sepsis is usually accompanied by cardiomyocyte apoptosis and myocardial depression. Protein kinase C (PKC) has been reported to be important in regulating cardiac function and apoptosis; however, which PKC isoform is involved in sepsis-induced myocardial apoptosis remains unknown.

Materials And Methods: A rat model of sepsis by cecal ligation and puncture was used.

Identification of minuscule inward currents as precursors to membrane electroporation-induced currents: real-time prediction of pore appearance.

Background/aims: The objective of this study is to examine the current signals in response to large hyperpolarizations with the aid of principal component analysis (PCA) to search for or even predict current fluctuations related to membrane electroporation-induced current (I(MEP)).

Methods: The characteristics of principal eigenvalues generated for I(MEP) and the current signals at 10 sec prior to the start of initial I(MEP) (I(Pre)) were examined. As membrane hyperpolarizations were applied at 0.

The inhibition of inwardly rectifying K+ channels by memantine in macrophages and microglial cells.

Background/aims: Memantine (MEM) can block N-methyl-D-aspartate receptors non-competitively and is recognized to exert anti-inflammatory action. Whether MEM and other related compounds produce any effects on K(+) currents in macrophages and in microglial cells is largely unknown. In this study, we investigated the effects of MEM and other related compounds on inwardly rectifying K(+) current (IK(IR)) in RAW 264.

Indomethacin inhibits cancer cell migration via attenuation of cellular calcium mobilization.

Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation.

Functional regulation of Alu element of human angiotensin-converting enzyme gene in neuron cells.

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and its protein activity have been widely implicated to be associated with Alzheimer's disease (AD). However, whether the insertion sequence, Alu element, in intron 16 of the human ACE gene plays a functional role remains uncertain. To investigate the influence of the I/D polymorphism on ACE promoter, we recombined the I and D form fragments with the human ACE promoter sequence before the reporter gene in pSEAP-Basic2 vector.

Inhibition of autophagy as a therapeutic strategy of iron-induced brain injury after hemorrhage.

Premenopausal women have better survival than men after intracerebral hemorrhage, which is associated with iron overproduction and autophagy induction. To examine the participation of neuronal autophagy and estrogen receptor α (ERα) in the E 2-mediated protection, PC12 neurons treated with Atg7 (autophagy-related protein 7) siRNA, rapamycin (an autophagy inducer), or Erα siRNA were applied. To study whether autophagy involves in β-estradiol 3-benzoate (E 2)-mediated neuroprotection against iron-induced striatal injury, castration and E 2 capsule implantation were performed at 2 weeks and 24 h, respectively, before ferrous citrate (FC) infusion into the caudate nucleus (CN) of Sprague Dawley male and female rats.

The decline of autophagy contributes to proximal tubular dysfunction during sepsis.

Severe sepsis associated with overproduction of tumor necrosis factor α and reactive oxygen species leads to energy depletion and cellular damage. Both reactive oxygen species and damaged organelles induce autophagy for recycling nutrients to combat pathological stress. To study whether autophagy plays a beneficial role in the pathogenesis of renal failure during sepsis, rats were subjected to cecal ligation and puncture (CLP) or sham operation.

Association of ORAI1 haplotypes with the risk of HLA-B27 positive ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The aetiology of ankylosing spondylitis is still unclear. Previous studies have indicated that genetics factors such as human leukocyte antigen HLA-B27 associates to AS susceptibility.

Differences in left ventricular cardiomyocyte loss induced by chronic intermittent hypoxia between spontaneously hypertensive and Wistar-Kyoto rats.

Rationale: Chronic intermittent hypoxia (CIH) is thought to induce several cardiovascular effects in patients with obstructive sleep apnoea (OSA). However, the effects of CIH on patients with long-standing hypertension are unknown.

Purpose: This prospective study aimed to investigate the influence of combined OSA and hypertension on cardiomyocyte death.

Sex-specific role of thioredoxin in neuroprotection against iron-induced brain injury conferred by estradiol.

Background And Purpose: Accumulation of iron after intracerebral hemorrhage causes free radical formation and oxidative damage resulting in liquefaction. The aim of this study was the investigation of molecular mechanisms underlying estrogen-mediated neuroprotective effect against iron-induced brain injury in vivo.

Methods: Age-matched male and female Sprague-Dawley rats were stereotaxically infused with either ferrous citrate (FC) or saline (10 muL) into the right caudate nucleus.

The molecular events occur during MK-801-induced cytochrome oxidase subunit II down-regulation in GT1-7 cells.

Previously, we showed that predominant expression of the N-methyl-D-aspartate (NMDA) receptor in the neurons of the sexually dimorphic nucleus of the preoptic area of male rats plays an important role in preventing neurons from apoptosis during sexual development. Blocking of the NMDA receptor by dizocilpine ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-iminemaleate (MK-801) causes down-regulation of some survival-related genes including cytochrome oxidase subunit II (COII), a mitochondria-encoded complex IV subunit, which in turn induces ATP depletion and the occurrence of apoptosis. The aim of this study is to investigate the molecular events during down-regulation of the COII gene expression induced by blocking of the NMDA receptor.

Arachidonic acid inhibits capacitative Ca2+ entry and activates non-capacitative Ca2+ entry in cultured astrocytes.

Arachidonic acid (AA) plays important physiological or pathophysiological roles. Here, we show in cultured rat astrocytes that: (i) endothelin-1 or thapsigargin (Tg) induces store-depleted activated Ca(2+) entry (CCE), which is inhibited by 2-aminoethoxydiphenyl borane (2-APB) or La(3+); (ii) AA (10 microM) and other unsaturated fatty acids (8,11,14-eicosatrienoic acid and gamma-linoleic acid) have an initial inhibitory effect on the CCE, due to AA- or fatty acid-induced internal acid load; (iii) after full activation of CCE, AA induces a further Ca(2+) influx, which is not inhibited by 2-APB or La(3+), indicating that AA activates a second Ca(2+) entry pathway, which coexists with CCE; and (iv) Tg or AA activates two independent and co-existing non-selective cation channels and the Tg-induced currents are initially inhibited by addition of AA or weak acids. A possible pathophysiological effect of the AA-induced [Ca](i) overload is to cause delayed cell death in astrocytes.

Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development.

The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that differential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), alpha-tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor.