Brainstem Circuits Triggering Saccades and Fixation.

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades.SIGNIFICANCE STATEMENT Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.

An infant case with hydrocephalus as the initial manifestation of Mycoplasma hominis-associated meningitis.

We report an infant with hydrocephalus as the initial manifestation of Mycoplasma hominis-associated meningitis, who recovered without appropriate antimicrobial treatment. The analysis of the 16S rRNA gene by polymerase chain reaction amplification using universal primers and pathogen-specific primers was useful for the diagnosis and the investigation of serial detection status of the pathogen. This method may be helpful for the assessment of the frequency and the prediction of severity in M. hominis-associated central nervous system infection in infants, and investigating the association between M. hominis and the development of hydrocephalus.

Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

Pilocytic astrocytoma presenting with atypical features on magnetic resonance imaging.

Pilocytic astrocytoma, which is classified as a grade I astrocytic tumor by the World Health Organization, is the most common type of glioma in children and young adults. Pilocytic astrocytoma generally appears as a well-circumscribed, contrast-enhancing lesion, frequently with cystic components on magnetic resonance imaging (MRI). However, it has been reported that the MRI appearance of pilocytic astrocytoma may be similar to that of high-grade gliomas in some cases. We here report on 6 cases of pilocytic astrocytoma with atypical MRI findings, including small cyst formation, heterogeneously enhancing tumor nodules, irregularly enhancing tumor nodules, and enhancing tumor nodules with internal hemorrhage. All tumors were successfully resected, and the histological diagnoses were pilocytic astrocytoma. When the tumor is located near a cerebral cistern or ventricle, the risk of leptomeningeal dissemination is increased. Furthermore, partial resection has also been associated with a higher risk of recurrence and leptomeningeal dissemination. To date, all but one patient are alive and recurrence-free. Because the preoperative diagnosis influences the decision on the extent of resection and because of the high risk of leptomeningeal dissemination associated with these tumors, careful and correct diagnosis by MRI is important.

Convergent synaptic inputs from the caudal fastigial nucleus and the superior colliculus onto pontine and pontomedullary reticulospinal neurons.

The caudal fastigial nucleus (FN) is known to be related to the control of eye movements and projects mainly to the contralateral reticular nuclei where excitatory and inhibitory burst neurons for saccades exist [the caudal portion of the nucleus reticularis pontis caudalis (NRPc), and the rostral portion of the nucleus reticularis gigantocellularis (NRG) respectively]. However, the exact reticular neurons targeted by caudal fastigioreticular cells remain unknown. We tried to determine the target reticular neurons of the caudal FN and superior colliculus (SC) by recording intracellular potentials from neurons in the NRPc and NRG of anesthetized cats. Neurons in the rostral NRG received bilateral, monosynaptic excitation from the caudal FNs, with contralateral predominance. They also received strong monosynaptic excitation from the rostral and caudal contralateral SC, and disynaptic excitation from the rostral ipsilateral SC. These reticular neurons with caudal fastigial monosynaptic excitation were not activated antidromically from the contralateral abducens nucleus, but most of them were reticulospinal neurons (RSNs) that were activated antidromically from the cervical cord. RSNs in the caudal NRPc received very weak monosynaptic excitation from only the contralateral caudal FN, and received either monosynaptic excitation only from the contralateral caudal SC, or monosynaptic and disynaptic excitation from the contralateral caudal and ipsilateral rostral SC, respectively. These results suggest that the caudal FN helps to control also head movements via RSNs targeted by the SC, and these RSNs with SC topographic input play different functional roles in head movements.

Pathways for Naturalistic Looking Behavior in Primate II. Superior Colliculus Integrates Parallel Top-down and Bottom-up Inputs.

Volitional signals for gaze control are provided by multiple parallel pathways converging on the midbrain superior colliculus (SC), whose deeper layers output to the brainstem gaze circuits. In the first of two papers (Takahashi and Veale, 2023), we described the properties of gaze behavior of several species under both laboratory and natural conditions, as well as the current understanding of the brainstem and spinal cord circuits implementing gaze control in primate. In this paper, we review the parallel pathways by which sensory and task information reaches SC and how these sensory and task signals interact within SC's multilayered structure. This includes both bottom-up (world statistics) signals mediated by sensory cortex, association cortex, and subcortical structures, as well as top-down (goal and task) influences which arrive via either direct excitatory pathways from cerebral cortex, or via indirect basal ganglia relays resulting in inhibition or dis-inhibition as appropriate for alternative behaviors. Models of attention such as saliency maps serve as convenient frameworks to organize our understanding of both the separate computations of each neural pathway, as well as the interaction between the multiple parallel pathways influencing gaze. While the spatial interactions between gaze's neural pathways are relatively well understood, the temporal interactions between and within pathways will be an important area of future study, requiring both improved technical methods for measurement and improvement of our understanding of how temporal dynamics results in the observed spatiotemporal allocation of gaze.

Severe subarachnoid hemorrhage associated with cerebral venous thrombosis in early pregnancy: a case report.

BACKGROUND: Cerebral venous thrombosis (CVT) rarely induces subarachnoid hemorrhage (SAH). During late pregnancy and puerperium, CVT is an uncommon but important cause of stroke. However, severe SAH resulting from CVT is extremely rare during early pregnancy. OBJECTIVE: We report on a rare case of severe SAH due to CVT, and discuss the potential pitfalls of CVT diagnosis in early pregnancy. CASE REPORT: A 32-year-old pregnant woman (9th week of pregnancy) presented with slight head dullness. Initial magnetic resonance imaging (MRI) revealed focal, abnormal signal intensity in the left thalamus. Nine days later, the patient developed a generalized seizure and severe SAH was detected with computed tomography (CT) scan. MRI and cerebral angiography revealed a completely thrombosed superior sagittal sinus, vein of Galen, straight sinus, and right transverse sinus. Transvaginal sonography indicated a missed abortion. The day after admission, the patient presented again with a progressive loss of consciousness and signs of herniation. The patient underwent emergency decompressive craniotomy, followed by intrauterine curettage. Two months later, she made an excellent recovery except for a slight visual field defect. CONCLUSIONS: A rare case of severe SAH due to CVT is reported, with emphasis on the potential pitfalls of CVT diagnosis in early pregnancy.

[Evaluation of the efforts of pharmaceutical care services before medical examination at an outpatient cancer chemotherapy clinic].

In the outpatient cancer chemotherapy clinic of Gifu University Hospital, pharmacists contributed to the provision of safe and efficacious cancer chemotherapy as full-time staff, together with doctors, nurses and other medical staff. Since April 2010, three pharmacists have been in charge of the provision of pharmaceutical care services(PCS)to all patients. Furthermore, pharmaceutical intervention before medical examination(pre-PCS)was initiated in May 2011. As a consequence, the time spent for patient education and monitoring significantly(p<0. 001)increased from 39. 7±3. 2min/patient in 2010 to 48. 0±2. 6min/patient in 2011. The number of proposals on prescriptions also significantly increased, 2. 5 times, compared to 2010. The percentage of the acceptance of proposals was 94% in fiscal year 2011. Importantly, pre-PCS improved the control of chemotherapy-induced nausea and vomiting, peripheral neuropathy and skin rash. These results suggest that pre-PCS by pharmacists would be beneficial to progress the quality of outpatient cancer chemotherapy.

Pathways for Naturalistic Looking Behavior in Primate I: Behavioral Characteristics and Brainstem Circuits.

Organisms control their visual worlds by moving their eyes, heads, and bodies. This control of "gaze" or "looking" is key to survival and intelligence, but our investigation of the underlying neural mechanisms in natural conditions is hindered by technical limitations. Recent advances have enabled measurement of both brain and behavior in freely moving animals in complex environments, expanding on historical head-fixed laboratory investigations. We juxtapose looking behavior as traditionally measured in the laboratory against looking behavior in naturalistic conditions, finding that behavior changes when animals are free to move or when stimuli have depth or sound. We specifically focus on the brainstem circuits driving gaze shifts and gaze stabilization. The overarching goal of this review is to reconcile historical understanding of the differential neural circuits for different "classes" of gaze shift with two inconvenient truths. (1) "classes" of gaze behavior are artificial. (2) The neural circuits historically identified to control each "class" of behavior do not operate in isolation during natural behavior. Instead, multiple pathways combine adaptively and non-linearly depending on individual experience. While the neural circuits for reflexive and voluntary gaze behaviors traverse somewhat independent brainstem and spinal cord circuits, both can be modulated by feedback, meaning that most gaze behaviors are learned rather than hardcoded. Despite this flexibility, there are broadly enumerable neural pathways commonly adopted among primate gaze systems. Parallel pathways which carry simultaneous evolutionary and homeostatic drives converge in superior colliculus, a layered midbrain structure which integrates and relays these volitional signals to brainstem gaze-control circuits.

Majority rule can help solve difficult tasks even when confident members opt out to serve individual interests.

When sharing a common goal, confident and competent members are often motivated to contribute to the group, boosting its decision performance. However, it is unclear whether this process remains effective when members can opt in or out of group decisions and prioritize individual interests. Our laboratory experiment (n = 63) and cognitive modeling showed that at the individual level, confidence, competence, and a preference for risk motivated participants' opt-out decisions. We then analyzed the group-level accuracy of majority decisions by creating many virtual groups of 25 members resampled from the 63 participants in the experiment. Whereas the majority decisions by voters who preferred to participate in group decision making were inferior to individual decisions by loners who opted out in an easy task, this was reversed in a difficult task. Bootstrap-simulation analyses decomposed these outcomes into the effects of a decrease in group size and a decrease in voters' accuracy accruing from the opt-in/out mechanism, demonstrating how these effects interacted with task difficulty. Our results suggest that the majority rule still works to tackle challenging problems even when individual interests are emphasized over collective performance, playing a functional as well as a democratic role in consensus decision making under uncertainty.

Quercetin and resveratrol inhibit ferroptosis independently of Nrf2-ARE activation in mouse hippocampal HT22 cells.

Oxidative stress is the central pathomechanism in multiple cell death pathways, including ferroptosis, a form of iron-dependent programmed cell death. Various phytochemicals, which include the inducers of the nuclear factor erythroid-2-related factor 2-antioxidant response element (Nrf2-ARE) transcription pathway, prevent ferroptosis. We recently reported that several compounds, such as the potent Nrf2-ARE inducer curcumin, protect mouse hippocampus-derived HT22 cells against ferroptosis independently of Nrf2-ARE activity. The present study characterized the anti-ferroptotic mechanisms of two additional Nrf2-ARE inducers, quercetin and resveratrol. Both compounds prevented erastin- and RSL3-induced ferroptosis of wild-type HT22 cells, and also blocked the exacerbated erastin- and RSL3-induced ferroptosis of Nrf2-knockdown HT22 cells. In both HT22 cells, quercetin and resveratrol blocked erastin- and RSL3-induced elevation in reactive oxygen species. These results suggest that the Nrf2-ARE pathway does protect against ferroptosis, but quercetin and resveratrol act by reducing oxidative stress independently of Nrf2-ARE induction. Quercetin and resveratrol also reduced Fe2+ concentrations in HT22 cells and in cell-free reactions. Thus, quercetin and resveratrol likely protect against erastin- and RSL3-induced ferroptosis by inhibiting the iron-catalyzed generation of hydroxyl radicals. Unlike quercetin, resveratrol cannot form a chelate structure with Fe2+ but the density functional theory computation demonstrates that resveratrol can form stable monodentate complexes with the alkene moiety and the electron-rich A ring.

Antiferroptotic Activities of Oxindole GIF-0726-r Derivatives: Involvement of Ferrous Iron Coordination and Free-Radical Scavenging Capacities.

Ferroptosis and oxytosis are iron- and oxidative stress-dependent cell death pathways strongly implicated in neurodegenerative diseases, cancers, and metabolic disorders. Therefore, specific inhibitors may have broad clinical applications. We previously reported that 3-[4-(dimethylamino)benzyl]-2-oxindole (GIF-0726-r) and derivatives protected the mouse hippocampal cell line HT22 against oxytosis/ferroptosis by suppressing reactive oxygen species (ROS) accumulation. In this study, we evaluated the biological activities of GIF-0726-r derivatives with modifications at the oxindole skeleton and other positions. The addition of a methyl, nitro, or bromo group to C-5 of the oxindole skeleton enhanced antiferroptotic efficacy on HT22 cells during membrane cystine-glutamate antiporter inhibition and ensued intracellular glutathione depletion. In contrast, the substitution of the dimethylamino group on the side chain phenyl ring with a methyl, nitro, or amine group dramatically suppressed antiferroptotic activity regardless of other modifications. Compounds with antiferroptotic activity also directly scavenged ROS and decreased free ferrous ions in both HT22 cells and cell-free reactions while those compounds without antiferroptotic activity had little effect on either ROS or ferrous-ion concentration. Unlike oxindole compounds, which we have previously reported, the antiferroptotic compounds had little effect on the nuclear factor erythroid-2-related factor 2-antioxidant response element pathway. Oxindole GIF-0726-r derivatives with a 4-(dimethylamino)benzyl moiety at C-3 and some types of bulky group at C-5 (whether electron-donating or electron-withdrawing) can suppress ferroptosis, warranting safety and efficacy evaluations in animal models of disease.

The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors.

Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.

Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells.

Cancer cells show constitutive upregulation of glycolysis, and the concentration of lactate thus produced correlates with prognosis. Here, we examined whether lactate concentration and lactate transporter expression are related to migration and invasion activity. We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness. To clarify the effects of MCT1 and MCT4 expression on invasion, we performed migration and invasion assays after transfection with siRNA specific for MCT1 or MCT4. Knockdown of MCT1 or MCT4 did not influence cell migration but reduced invasion; this was also observed for knockdown of the lactate transporter-associated protein basigin. We also demonstrated that both expression and activity of MMP9 and MMP2 were not correlated with invasion activity and not regulated by MCT1, MCT4 and basigin. Furthermore, the addition of lactate did not increase migration and invasion activity, but low concentration of 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), a general anion channel blocker, as well as other MCT inhibitors quercetin and simvastatin, inhibited cell invasion without influencing migration activity and the cellular expression of MCT1 and MCT4. This is the first report suggesting that lactate transporters are involved in human cancer cell invasiveness. As such, these proteins may be promising targets for the prevention of cancer invasion and metastasis.

Dural attachment of intracranial meningiomas: evaluation with contrast-enhanced three-dimensional fast imaging with steady-state acquisition (FIESTA) at 3 T.

INTRODUCTION: The purpose of this study was to evaluate the role of contrast-enhanced fast imaging with steady-state acquisition (CE-FIESTA) for assessing whether dural attachment in intracranial meningiomas is adhesive or not by correlation with intraoperative findings. METHODS: Fourteen consecutive patients who were candidates for surgical treatment of meningiomas were prospectively analyzed with preoperative magnetic resonance imaging, including CE-FIESTA at 3 T. First, two neuroradiologists assessed several characteristics of the attachment of the meningioma to the dura mater or skull base on CE-FIESTA images. Second, the surgical findings of adhesion at the dural attachment of meningiomas were evaluated by two neurosurgeons. Finally, the CE-FIESTA findings were correlated with the surgical findings by one neurosurgeon and one neuroradiologist by consensus. RESULTS: CE-FIESTA clearly depicted a hypointense marginal line at the attachment site of the meningioma. When CE-FIESTA revealed smooth marginal lines or hyperintense zones along the marginal lines, tumors were detached easily from the dura mater. On the contrary, when CE-FIESTA showed an irregularity, such as partial disruption of the marginal lines, vessels, or bony hyperostosis, the tumors tended to adhere firmly to the dura mater, which was found to contain small vessels and fine fibrous tissues. CONCLUSIONS: There seems to be an excellent correlation between the characteristics of dural attachment of meningiomas on CE-FIESTA images and intraoperative findings. Therefore, for operative planning, CE-FIESTA may provide useful information regarding the adhesiveness of dural attachment.

Preoperative radiological evaluation and surgical strategy for the preservation of visual acuity in patients with skull base meningiomas--two case reports.

Two women aged 48 and 73 years, respectively, presented with unilateral visual disturbance. On admission, magnetic resonance imaging (MRI) showed an extraaxial mass in the parasellar region. Contrast-enhanced fast imaging with steady-state acquisition (CE-FIESTA) showed that the optic nerves were compressed and encased by the tumors. At an early stage of surgery, we performed decompression of the optic nerves to avoid optic nerve injury. Both the patients were relieved of visual disturbances without any postoperative neurological deficit. In conclusion, CE-FIESTA is a useful diagnostic tool for preoperative evaluation of the optic nerves in patients with skull base meningiomas. Decompression of the optic nerves should be performed at an early stage of surgery in meningioma patients presenting with visual disturbance.

Surgical treatment for a ruptured true posterior communicating artery aneurysm arising on the fetal-type posterior communicating artery--two case reports and review of the literature.

Only a small number of aneurysms arising on the posterior communicating artery itself (true Pcom aneurysm) have been reported. We report two cases of ruptured true Pcom aneurysms with some characteristic features of true Pcom aneurysm. A 43 year old man suffering from subarachnoid hemorrhage (SAH) had an aneurysm arising on the fetal-type Pcom artery itself, and underwent surgery for clipping. Most of the aneurysm was buried in the temporal lobe, so retraction of the temporal lobe was mandatory. During the retraction, premature rupture was encountered. After tentative dome clipping and the control of bleeding, complete clipping was achieved. Another patient, a 71 year old woman presenting with consciousness disturbance due to SAH, had an aneurysm on the fetal-type Pcom artery itself, and underwent surgery for clipping. It has been generally considered that hemodynamic factor plays an important role in the formation, the growth, and the rupture of the cerebral aneurysm. This factor is especially significant in true Pcom aneurysm formation and rupture. According to the literature, a combination of fetal type Pcom and formation of the true Pcom aneurysm has been reported in most cases (81.8%). Most of the aneurysm can be buried in the temporal lobe, and the retraction of the temporal lobe during the dissection of the neck would be necessary, which causes premature rupture of the true Pcom aneurysm. In the surgery for a true Pcom aneurysm, we should be aware of possible premature rupture when temporal lobe retraction is necessary.

Neural Circuits of Inputs and Outputs of the Cerebellar Cortex and Nuclei.

This article is dedicated to the memory of Masao Ito. Masao Ito made numerous important contributions revealing the function of the cerebellum in motor control. His pioneering contributions to cerebellar physiology began with his discovery of inhibition and disinhibition of target neurons by cerebellar Purkinje cells, and his discovery of the presence of long-term depression in parallel fiber-Purkinje cell synapses. Purkinje cells formed the nodal point of Masao Ito's landmark model of motor control by the cerebellum. These discoveries became the basis for his ideas regarding the flocculus hypothesis, the adaptive motor control system, and motor learning by the cerebellum, inspiring many new experiments to test his hypotheses. This article will trace the achievements of Ito and colleagues in analyzing the neural circuits of the input-output organization of the cerebellar cortex and nuclei, particularly with respect to motor control. The article will discuss some of the important issues that have been solved and also those that remain to be solved for our understanding of motor control by the cerebellum.

Identification of novel neuroprotective N,N-dimethylaniline derivatives that prevent oxytosis/ferroptosis and localize to late endosomes and lysosomes.

Oxidative stress has been implicated in the aging process and the progression of many neurodegenerative disorders. We previously reported that a novel oxindole compound, GIF-0726-r, effectively prevents endogenous oxidative stress, such as oxytosis/ferroptosis, an iron-dependent form of non-apoptotic cell death, in mouse hippocampal cells. In this study, using two hundred compounds that were developed based on the structure-activity relationship of GIF-0726-r, we screened for the most potent compounds that prevent glutamate- and erastin-induced oxytosis and ferroptosis. Using submicromolar concentrations, we identified nine neuroprotective compounds that have N,N-dimethylaniline as a common structure but no longer contain an oxindole ring. The most potent derivatives, GIF-2114 and GIF-2197-r (the racemate of GIF-2115 and GIF-2196), did not affect glutathione levels, had no antioxidant activity in vitro, or ability to activate the Nrf2 pathway, but prevented oxytosis/ferroptosis via reducing reactive oxygen production and decreasing ferrous ions. Furthermore, we developed fluorescent probes of GIF-2114 and GIF-2197-r to image their distribution in live cells and found that they preferentially accumulated in late endosomes/lysosomes, which play a central role in iron metabolism. These results suggest that GIF-2114 and GIF-2197-r protect hippocampal cells from oxytosis/ferroptosis by targeting late endosomes and lysosomes, as well as decreasing ferrous ions.

Y-box binding protein-1 is a novel molecular target for tumor vessels.

Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many reports indicate that YB-1 is highly expressed in tumor cells and is a marker for tumor aggressiveness and clinical prognosis. Here, we show clear evidence that YB-1 is expressed in the angiogenic endothelial cells of various tumors, such as glioblastoma, esophageal cancer, gastric cancer, colon cancer, and lung cancer, as well as in tumor cells. YB-1 was highly expressed in glomeruloid microvascular endothelial cells of brain tumors and microvessels in the desmoplastic region around multiple solid tumors. On the other hand, no or low YB-1 expression was observed in normal angiogenic endothelial cells from fetal kidney, newborn lung, and placenta. The endothelial cells in inflammatory regions of granulomas were also weakly labeled. Knockdown of YB-1 expression by small-interfering RNA induced G1 cell cycle arrest and inhibited the growth of human umbilical vein endothelial cells stimulated by growth factors. Taken together, YB-1 plays an important role in the growth of not only tumor cells but also tumor-associated endothelial cells, suggesting that YB-1 is a promising target for cancer therapy.