RARRES2's impact on lipid metabolism in triplenegative breast cancer:a pathway to brain metastasis

Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.

Lactate metabolism in neurodegenerative diseases

Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

We examined a total of 16 children with epileptic encephalopathy using fluorine-18-fluoro-2-deoxy-D-glucose （18F-FDG） positron emission computed tomography （PET）, magnetic resonance imaging （MRI） and electroencephalography. Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with I^F-FDG PET imaging. MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia. In cases with Lennox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis. MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake. In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and ~aF-FDG PET exhibited multifocal glucose hypometabolism. Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity. In addition, ~SF-FDG PET imaging after treatment was consistent with clinical outcomes. These findings indicate that ~SF-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.

Iron metabolism, oxidative stress, and neonatal brain injury

The brain injury associated with neonatal hypoxia ischemia（HI）is a major contributor to neonatal mortality and neurodevelopment retardation.Approximately 30-40%of infants with brain injury will die and 20-40%of survivors will develop significant neurological disorders and lifelong disability.

Effects of microwave radiation on brain energy metabolism and related mechanisms

With the rapid development of electronic technologies, anxiety regarding the potential health hazards induced by microwave radiation(MW) has been growing in recent years. The brain is one of the most sensitive target organs for microwave radiation, where mitochondrial injury occurs earlier and more severely than in other organs. Energy metabolism disorders do play an important role during the process of microwave radiation-induced brain damage. In this paper, we will review the biological effects of microwave radiation, the features of brain energy supply and consumption and the effects of microwave radiation on mitochondrial energy metabolism and potential related mechanisms.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

Monitoring Brain and Spinal Cord Metabolism and Function

Monitoring the metabolism and function of the central nervous system not only is an old idea but also is a topic that is of increasing interest to the technological evolution. Beside the optimization of cerebral and spinal cord perfusion and the preservation of vasoreactivity to ensure the viability of cerebral tissues and structures, we want to know more and more about the real intimate situation of these organs in real time at the patient’s bedside. To this end, several tracks have been explored during the two last decades, leading to the development of numerous concepts and the conception of various monitoring systems. One of the main problems is to characterize the respective strong points and weaknesses of those ones and to conclude regarding their individual relevance and value in current clinical practice. It is more and more clear that the combination of different categories of monitoring is a way to try to find the most valuable technological compromise, to increase the chance of prediction or of early detection of intercurrent deleterious events corresponding to the concept of multimodality. The intraoperative period and the intensive care goals and targets are appreciably different. This is the reason for the attempt to define different and distinct sets of goals and targets for the intraoperative anesthetic setting and for the intensive care unit.

Evaluation of brain tumor metabolism with [^(11)C] choline PET and ~1H-MRS.

BACKGROUND:The signal of choline containing compounds（Cho）in proton magnetic resonance spectroscopy（1H-MRS）is elevated in brain tumors.[11C]choline uptake as assessed using positron emission tomography（PET）has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[11C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and1H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as

Effects of mild hypothermia on cerebral oxygen metabolism and brain injury in patients with severe craniocerebral injury

Objective: To investigate the effects of mild hypothermia on cerebral oxygen metabolism and brain injury in patients with severe craniocerebral injury. Methods: A total of 78 patients with severe craniocerebral injury who underwent emergency treatment in Huanggang Central Hospital between September 2015 and May 2017 were selected as the research subjects and divided into control group (n=39) and mild hypothermia group (n=39) by random number table. Control group received clinical standard large trauma craniotomy for severe craniocerebral injury, and mild hypothermia group received routine surgery and postoperative mild hypothermia therapy. The cerebral oxygen metabolism and brain injury in two groups of patients were detected immediately after admission (T0), 1 week after treatment (T1) and 4 weeks after treatment (T2). Results: At T0, there was no statistically significant difference in the levels of cerebral oxygen metabolism indexes, cerebral blood flow parameters and brain injury markers between the two groups. At T1 and T2, PO2 levels in mild hypothermia group were higher than those in control group while Da-jvO2 levels were lower than those in control group;cerebral blood flow parameters Vs and Wv levels were higher than those in control group while PI levels were lower than those in control group;brain injury markers MBP, AQP-4 and S-100B contents were lower than those in control group while BDNF contents were higher than those in control group. Conclusion: Adjuvant mild hypothermia therapy after routine surgery may further reduce the cerebral oxygen metabolism and relieve the brain injury in patients with severe craniocerebral injury.

Diffusion tensor imaging and proton magnetic resonance spectroscopy in brain tumor Correlation between structure and metabolism

Proton magnetic resonance spectroscopy and diffusion tensor imaging are non-invasive techniques used to detect metabolites and water diffusion in vivo. Previous studies have confirmed a positive correlation of individual fractional anisotropy values with N-acetylaspartate/creatine and N-acetylaspartate/choline ratios in tumors, edema, and normal white matter. This study divided the brain parenchyma into tumor, pedtumoral edema, and normal-appearing white matter according to MRI data, and analyzed the correlation of metabolites with water molecular diffusion. Results demonstrated that in normal-appearing white matter, N-acetylaspartate/creatine ratios were positively correlated with fractional anisotropy values, negatively correlated with radial diffusivities, and positively correlated with maximum eigenvalues. Maximum eigenvalues and radial diffusivities in peritumoral edema showed a negative correlation with choline, N-acetylaspartate, and creatine. Radial diffusivities in tumor demonstrated a negative correlation with choline. These data suggest that the relationship between metabolism and structure is markedly changed from normal white matter to peritumoral edema and tumor. Neural metabolism in the peritumoral edema area decreased with expanding extracellular space. The normal relationship of neural function and microstructure disappeared in the tumor region.

Quiet rest ameliorates biochemical metabolism in the brain in a simple concussion rabbit model Evaluation of hydrogen proton magnetic resonance spectroscopy

The present study analyzed changes in the biochemical metabolites N-acetyl aspartate, choline, and creatine in a simple concussion rabbit model following quiet rest, hyperbaric oxygen therapy, or interference stimulation through the use of hydrogen proton magnetic resonance spectroscopy detection. Experimental findings showed that brain N-acetyl aspartate and choline peak values significantly decreased, while creatine peak values significantly increased following simple concussion. Following treatments, N-acetyl aspartate and choline peaks returned to normal levels in the quiet rest and hyperbaric oxygen therapy groups, but no changes were observed in the interference stimulation group. Results demonstrated abnormal changes in the brain biochemical metabolism environment following simple concussion. Quiet rest was shown to play an important role in restoration of biochemical metabolism following simple concussion.

Reproducibility of perfusion CT derived CBV and rCBV measurements with different slice thickness in patients with brain neoplasms

Objective:To assess inter-and intraobserver reproducibility for measuring perfusion CT derived cerebral blood volume (CBV) and relative cerebral blood volume (rCBV) with different slice thickness in patients with brain neoplasms. Meth- ods: Three independent observers who were blinded to the histopathologic diagnosis performed perfusion derived CBV and rCBV measurements with 5 mm and 10 mm slice thickness in 52 patients with various cerebral neoplasms. The results of the measurements with different slice thickness were compared. Calculation of coefficient of variation (CV), and relative paired difference of the measurements were used to determine the levels of inter- and intraobserver reproducibility. Results: The differences of CBV and rCBV measurements between different slice thickness groups were statistically significant (P < 0.05) respectively in observer 2, and were not significant in the other two observers (P > 0.05). For the same slice thickness, both the difference of CBV and rCBV measurements among the three observers were not statistically significant. Interobserver CV and relative paired difference of the measurements with 10 mm slice thickness group were slightly lower than those of 5 mm slice thickness group. Interobserver CV and relative paired difference of CBV group were slightly lower than those of rCBV group. The intraobserver differences of CBV and rCBV in 10 mm slice thickness group were statistically significant for observer 2 respectively. No other intraobserver differences of measurements were statistically significant. CV and relative paired difference of intraobserver CBV and rCBV measurements for observer 2 were significantly higher than for the other two observers. Conclusion: High reproducibility of CBV and rCBV measurements was acquired with the two different slice thickness. Suitable training may be helpful to maintain a high level of consistency for measurements.

The Association between Cellular Phone Usage and Brain Neoplasms

Background: The association between cellular phones and brain tumors is a question that is frequently asked of the medical and scientific community. The prevalence of cell phone use and the significant morbidity and mortality of brain tumors contribute to this pairing. Cell phones are known to emit radio frequency energy in the form of both ionizing and non-ionizing radiation. Ionizing radiation is known to be within X-rays, which do have an association with cancer. Objective: To assess if the use of the cell phone has an association with brain tumors. Methods: The searches performed through PubMed were conducted to find studies that sought to provide evidence as to whether or not increased cell phone exposure contributed to the development of brain tumors. Also searched for was increased regional metabolism of the brain with the use of the cell phone switched in the on position. Studies were restricted to being published during or after the year 2000 and presented in the English language. Results: The studies largely support the conclusion that cell phone usage does not lead to the development of brain cancer. Studies employed different strategies, such as the prospective cohort and case-control studies to reach this conclusion. Both studies failed to show statistically significant evidence that cell phones were associated with brain tumors of the central nervous system. Conclusions: Questions raised by crossover studies demonstrating increased regional brain glucose metabolism continue to remain largely unanswered by current research and remain a starting point for future research. The prevalence of the issue strengthens its position among others as a matter that the medical community must continue to address to meet the needs of an increasingly exposed patient population. The overall hypothesis that cell phone usage does not lead to the development of brain tumors was supported.

The effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury

Objective To explore effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury. Methods 71 cases were divided into three groups according age: group A( 【 30 years) ,group B ( 30 ～ 50 years) 。

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.

In vivo imaging of structural,metabolic and functional brain changes in glaucoma

Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.

Resuscitating acupuncture therapy for glucose metabolism in acute cerebral infarction of basal ganglia

BACKGROUND： Acupuncture can improve motor function in patients with cerebral infarction, and activate brain glucose metabolism in relevant brain areas. However, the association between encephalic region activation and acupuncture, as well as the clinical significance of activation remain unclear. OBJECTIVE： Through the use of positron emission tomography-computed tomography （PET-CT）, acute cerebral infarction patients were analyzed for global cerebral metabolism, cerebral infarction focus, peripheral edema, and pyramidal tract pathway changes, which were directly related to clinical symptoms. The influence of resuscitating acupuncture on cerebral glucose metabolism was analyzed in patients with acute cerebral infarction in basal ganglia. DESIGN, TIME AND SETTNG： Randomized, controlled, clinical trials were performed from March 2007 to October 2008 at the PET-CT Center of the General Hospital of Tianjin Medical University, China. PARTICIPANTS： Twelve patients with acute basal ganglia infarction were recruited from the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin Chinese Medicine Hospital, and Affiliated Hospital of Medical College of Chinese People＇s Armed Police Force. METHODS： The cerebral infarcted patients were randomly assigned to acupuncture and control groups. In addition to routine treatment, the acupuncture group was treated by acupuncture at the main acupoints for resuscitation [Neiguan （PC 6）, Renzhong （DU 26）, and Sanyinjiao （SP 6）], while the control group received routine treatment. MAIN OUTCOME MEASURES： Before and after treatment, patients with acute cerebral infarction were evaluated for global brain, cerebral infarction focus, and surrounding edema and glucose metabolism in encephalic region of pyramidal tract conduction by 18-labeled fluorodeoxyglucose for PET-CT imaging. RESULTS： The resuscitating acupuncture therapy can significantly activate the metabolism of global brain, infarction center and surrounding edema in patients with cerebral infarction in basal ganglia, also has effects on the activation of glucose metabolism in the encephalic regions of pyramidal tract pathway （P 〈 0.05）. CONCLUSION： Resuscitating acupuncture was superior to routine treatment for significantly activating glucose metabolism in patients with acute cerebral basal ganglia infarction.

METABOLIC KINETICS OF BRAIN MUSCARINIC CHOLINERGIC RECEPTORS IN NORMAL AND HYPOTHYROID MICE

A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h-1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h ·mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h-1 in hypothyroid vs. 0.0356±0.0021 h-1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M- receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism.