Retraction of "Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2".

[This retracts the article DOI: 10.1021/acsomega.3c01296.

Corrigendum: TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis after experimental subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fncel.2022.

Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2.

Extracellular signal-regulated kinase 1 and 2 (Erk1/2) signaling has been shown to be involved in brain injury after subarachnoid hemorrhage (SAH). A first-in-human phase I study reported that ravoxertinib hydrochloride (RAH), a novel Erk1/2 inhibitor, has an acceptable safety profile and pharmacodynamic effects. Here, we showed that the level of Erk1/2 phosphorylation (p-Erk1/2) was significantly increased in the cerebrospinal fluid (CSF) of aneurysmal subarachnoid hemorrhage (aSAH) patients who developed poor outcomes.

TAT-HSP27 Peptide Improves Neurologic Deficits Reducing Apoptosis After Experimental Subarachnoid Hemorrhage.

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified.

LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway.

Chemoresistance is the primary cause of the poor outcome of glioblastoma multiforme (GBM) therapy. Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) is involved in the growth and proliferation of several types of cancer, including gastric cancer and ovarian cancer. Therefore, the aim of the present study was to investigate the role of LGR6 in GBM malignancy and chemoresistance.

Treatment of primary cardiac angiosarcoma in a 35 weeks pregnant woman.

Background: Cardiac angiosarcoma is a rare but highly malignant cardiac tumor. It is characterized by poor prognosis, and current treatment approaches are not effective.

Case Presentation: A 37-year-old female with 35 weeks pregnancy experienced chest tightness and shortness of breath for 1 month.

Ifenprodil Improves Long-Term Neurologic Deficits Through Antagonizing Glutamate-Induced Excitotoxicity After Experimental Subarachnoid Hemorrhage.

Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome.

Negative Allosteric Modulator of mGluR1 Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model.

CCT128930 induces G1-phase arrest and apoptosis and synergistically enhances the anticancer efficiency of VS5584 in human osteosarcoma cells.

Osteosarcoma is a highly invasive primary malignant bone tumor. PI3K/mTOR pathway plays a key role in tumor progression, and inhibition of PI3K/mTOR pathway represents a novel strategy in therapy of osteosarcoma. CCT128930 and VS5584 are both inhibitors of PI3K/mTOR, but the anticancer mechanism of CCT128930 or/and VS5584 against human osteosarcoma cells remains unclear.

Early High Cerebrospinal Fluid Glutamate: A Potential Predictor for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Early identification of cerebrospinal fluid (CSF) markers is helpful for warning of impending DCI. This study assessed whether early high CSF glutamate levels can be observed in aSAH patients who later developed DCI.

VS-5584 Inhibits Human Osteosarcoma Cells Growth by Induction of G1- phase Arrest through Regulating PI3K/mTOR and MAPK Pathways.

Background: Activation of the PI3K/mTOR signaling pathway plays a key role in the progression of human osteosarcoma. Studies have confirmed that VS-5584 was a novel inhibitor of the PI3K/mTOR pathway, and displayed potential anticancer activity.

Objective: To explore the anticancer effect and underlying mechanism of VS-5584 against the growth of human osteosarcoma cells.

Selective mGluR1 Negative Allosteric Modulator Reduces Blood-Brain Barrier Permeability and Cerebral Edema After Experimental Subarachnoid Hemorrhage.

The blood-brain barrier (BBB) disruption leads to the vasogenic brain edema and contributes to the early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the BBB damage following SAH are poorly understood. Here we reported that the neurotransmitter glutamate of cerebrospinal fluid (CSF) was dramatically increased in SAH patients with symptoms of cerebral edema.

Selenium-Containing Protein From Selenium-Enriched Attenuates Cisplatin-Induced Apoptosis in MC3T3-E1 Mouse Preosteoblast by Inhibiting Mitochondrial Dysfunction and ROS-Mediated Oxidative Damage.

Accumulated evidences have verified that cancer chemotherapy may increase the risk of osteoporosis and severely affected the life quality. Osteoclasts hyperactivation was commonly accepted as the major pathogenesis of osteoporosis. However, the role of osteoblasts dysfunction in osteoporosis was little investigated.

Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.

Background: Temozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention.

Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity and by Inhibiting Mitochondrial Dysfunction and Oxidative Damage.

Homocysteine (Hcy) as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD). Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX) as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction.

GLRB variants regulate nearby gene expression in human brain tissues.

A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis.

Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes.

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk.

Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet.

The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice.

Rationale: Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic.

EXOC3L2 rs597668 variant contributes to Alzheimer's disease susceptibility in Asian population.

Recent genome-wide association studies have established the association between EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population. However, recent studies reported inconsistent results in Asian population. Here, we performed a systematic review and meta-analysis to evaluate the impact of rs597668 on AD risk in Asian population using a total of 8686 samples including 2855 cases and 5831 controls.

Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral Hemorrhage in Rats.

Carnosine, an endogenous dipeptide (β-alanyl-L-histidine), exerts multiple neuroprotective properties, but its role in intracerebral hemorrhage (ICH) remains unclear. This study investigates the effect of Carnosine on brain injury using the rat ICH model, which is established by type IV collagenase caudatum infusion. The results indicate that intraperitoneal administration of Carnosine (1000 mg/kg) significantly attenuates brain edema, blood-brain barrier (BBB) disruption, oxidative stress, microglia activation and neuronal apoptosis of perihematoma at 72 h following ICH in rats models, as convinced by preventing the disruption of tight junction protein ZO-1, occludin and claudin-5, followed by the decrease of ROS, MDA, 3-NT, 8-OHDG level and the increase of GSH-Px and SOD activity, then followed by the decline of Iba-1, ED-1, active caspase-3 and TUNEL positive cells and the decrease of IL-1β, IL-6, TNF-α, active caspase-3 and cytochrome c level.

Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage.

The CD4CD25 regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model.

Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells.

Autophagy modulation has been considered as a potential therapeutic strategy for lung diseases. The PI3K-Akt-mTOR pathway may be one of the main targets for regulation of autophagy. We previously reported that a PI3K/mTOR dual inhibitor PF-04691502 suppressed hepatoma cells growth in vitro.