Modulation of Second Messenger Signaling in the Brain Through PDE4 and PDE5 Inhibition: Therapeutic Implications for Neurological Disorders.

Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca) and other metal ions, such as zinc (Zn) and magnesium (Mg), into the cytosol. This Ca influx at the presynaptic terminal triggers the release of Zn and glutamate to the postsynaptic terminal.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP).

The effectiveness of acupuncture as an adjunctive therapy to oral pharmacological medication in patient with knee osteoarthritis: A systematic review and meta-analysis.

Background: We aimed to find out whether the combined treatment of acupuncture and oral medication is more effective than sole oral medication in reducing pain and improving knee function at the end of treatment and after short-term period (4-6 weeks after treatment). Second, if it is effective, we investigated whether the effect surpasses the minimal clinically important difference.

Methods: Articles published between January 1, 1992, and August 31, 2022, were searched in PubMed, Cochrane, and Embase.

CPR quality with rotation of every 1 versus 2 minutes as characteristics of rescuers: A randomized crossover simulation study.

Background: Fatigue and rotation time are key factors affecting the quality of cardiopulmonary resuscitation (CPR). This study aimed to investigate the effects of rotation time on CPR duration, and sex on chest compression quality.

Methods: In this randomized crossover simulation study, we enrolled 100 paramedic students stratified by sex and randomly grouped into 28 male and 22 female pairs.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes.

Acid Sphingomyelinase Inhibitor, Imipramine, Reduces Hippocampal Neuronal Death after Traumatic Brain Injury.

Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells.

Unintentional fatal toxicity due to nicotine chewing gum: A case report.

Rationale: Since tobacco contains numerous harmful substances, besides nicotine, which is addictive, smoking cessation products and tobacco alternatives, such as electronic (e-) cigarettes, nicotine chewing gums, and patches, are being widely used. Nicotine gums are consumed orally. The nicotine from the gum is absorbed at a slower rate than that from e-cigarettes, and the former remains in the bloodstream for a longer period.

Low-voltage Activating K Channels in Cochlear Afferent Nerve Fiber Dendrites.

Cochlear afferent nerve fibers (ANF) are the first neurons in the ascending auditory pathway. We investigated the low-voltage activating K channels expressed in ANF dendrites using isolated rat cochlear segments. Whole cell patch clamp recordings were made from the dendritic terminals of ANFs.

Effects of dynamic response to coronavirus disease outbreak in a regional emergency medical center: A retrospective study.

Emergency departments (EDs) are on the frontline of the coronavirus disease (COVID-19) outbreak. To resolve the abrupt overloading of COVID-19-suspected patients in a community, each ED needs to respond in various ways. In our hospital, we increased the isolation beds through temporary remodeling and by performing in-hospital COVID-19 polymerase chain reaction testing rather than outsourcing them.

Comparison of the effects of shortening rest intervals on the quality of cardiopulmonary resuscitation, physiological parameters, and hemodynamic parameters in well-trained rescuers: Randomized simulation study.

Background: Cardiopulmonary resuscitation (CPR) performance depends on individual ability and training. Well-trained or professional rescuers can maintain high-quality CPR for longer than laypeople. This study aimed to examine the effects of reducing resting intervals on CPR performance, physiological parameters, and hemodynamic parameters during prolonged CPR in well-trained providers.

Impact of the coronavirus disease 2019 outbreak on the transportation of patients requiring emergency care.

The first confirmed community transmission of coronavirus disease 2019 in Daegu Metropolitan City, South Korea, occurred on February 18, 2020. In the following 70-day period, approximately 6000 new cases occurred, severely impacting the medical service system. This study investigated the crisis-impact on the local emergency transport system.

Involvement of peroxiredoxin 2 in cumulus expansion and oocyte maturation in mice.

Peroxiredoxin 2 (Prdx2), an antioxidant enzyme, is expressed in the ovary during the ovulatory process. The aim of the present study was to examine the physiological role of Prdx2 during ovulation using Prdx2-knockout mice and mouse cumulus-oocyte complex (COC) from WT mice. Two days of treatment of immature mice (21-23 days old) with equine chorionic gonadotrophin and followed by treatment with human chorionic gonadotrophin greatly impaired cumulus expansion and oocyte maturation in Prdx2-knockout but not wild-type mice.

MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.

The cell surface receptor tyrosine kinase (RTK) exists in a dynamic state, however, it remains unknown how single membrane-spanning RTK proteins are retained in the plasma membrane before their activation. This study was undertaken to investigate how RTK proteins are anchored in the plasma membrane before they bind with their respective extracellular ligands for activation through protein-protein interaction, co-localization, and functional phenotype studies. Here we show that unconventional myosin-I MYO1D functions to hold members of the EGFR family (except ErbB3) at the plasma membrane.

Noxa mitochondrial targeting domain induces necrosis via VDAC2 and mitochondrial catastrophe.

Noxa, a Bcl-2 homology 3 (BH3)-only protein of the Bcl-2 family, is responsive to cell stresses and triggers apoptosis by binding the prosurvival Bcl-2-like proteins Mcl1, Bcl, and Bcl2A1. Although the Noxa BH3 domain is necessary to induce apoptosis, the mitochondrial targeting domain (MTD) of Noxa functions as a pronecrotic domain, an inducer of mitochondrial fragmentation, and delivery to mitochondria. In this study, we demonstrate that the extended MTD (eMTD) peptide induces necrotic cell death by interaction with the VDAC2 protein.

Acute dystonic reaction induced by a single dose of clebopride: A case report.

Rationale: Clebopride is known as a dopamine antagonist used for alleviating emetic symptoms with minimal side effects. Herein, we report a case of acute dystonic reaction possibly caused by administration of clebopride in a young male.

Patient Concerns: A 19-year-old with no special medical conditions, visited a local clinic complaining of abdominal discomfort, associated with nausea and vomiting.

Improved memory and reduced anxiety in δ-catenin transgenic mice.

δ-Catenin is abundant in the brain and affects its synaptic plasticity. Furthermore, loss of δ-catenin is related to the deficits of learning and memory, mental retardation (cri-du-chat syndrome), and autism. A few studies about δ-catenin deficiency mice were performed.

p300/CBP-associated factor promotes autophagic degradation of δ-catenin through acetylation and decreases prostate cancer tumorigenicity.

δ-Catenin shares common binding partners with β-catenin. As acetylation and deacetylation regulate β-catenin stability, we searched for histone acetyltransferases (HATs) or histone deacetylases (HDACs) affecting δ-catenin acetylation status and protein levels. We showed that p300/CBP-associated factor (PCAF) directly bound to and acetylated δ-catenin, whereas several class I and class II HDACs reversed this effect.

Differential Expression of Ca-buffering Protein Calretinin in Cochlear Afferent Fibers: A Possible Link to Vulnerability to Traumatic Noise.

The synaptic contacts of cochlear afferent fibers (CAFs) with inner hair cells (IHCs) are spatially segregated according to their firing properties. CAFs also exhibit spatially segregated vulnerabilities to noise. The CAF fibers contacting the modiolar side of IHCs tend to be more vulnerable.