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Topic Review
HMGB1 and Post-Aneurysmal Subarachnoid Hemorrhage
Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by a robust sterile inflammatory response immediately after the subarachnoidal bleed. Several damage-associated molecular pattern molecules (DAMPs) are liberated upon injury of the brain cells from different intracellular compartments and have the capability to activate immune cells through the ligation of their cognizant receptors (pattern recognition receptors (PRRs)). Among them, high mobility group box-1 (HMGB1), which acts normally as a transcription factor, when released extracellularly upregulates inflammation due to its interaction with TLR-2, TLR-4 and RAGE during early brain injury after aSAH. However, recent investigations show that different isoforms of HMGB1 exist and may dominate during different phases of the brain injury with different consequences. Surprisingly, the oxidized isoform of HMGB1 plays an anti-inflammatory and pro-resovling role contrary to well accepted pro-inflammatory role of HMGB1 after aSAH.
  • 259
  • 17 Oct 2022
Topic Review
Matrix Vesicle-Mediated and Osteocytic Regulation of Bone Mineralization
Bone mineralization entails two mineralization phases: primary and secondary mineralization. Primary mineralization is achieved when matrix vesicles are secreted by osteoblasts, and thereafter, bone mineral density gradually increases during secondary mineralization. Nearby extracellular phosphate ions (PO43−) flow into the vesicles via membrane transporters and enzymes located on the vesicles’ membranes, while calcium ions (Ca2+), abundant in the tissue fluid, are also transported into the vesicles. The accumulation of Ca2+ and PO43− in the matrix vesicles induces crystal nucleation and growth. The calcium phosphate crystals grow radially within the vesicle, penetrate the vesicle’s membrane, and continue to grow outside the vesicle, ultimately forming mineralized nodules. The mineralized nodules then attach to collagen fibrils, mineralizing them from the contact sites (i.e., collagen mineralization). Afterward, the bone mineral density gradually increases during the secondary mineralization process.
  • 510
  • 28 Sep 2022
Topic Review
The Na+/H+ Exchangers in Cardiac Physiology Regulation
The Na+/H+ exchangers (NHEs) are membrane transporters that exchange one intracellular pro-ton for one extracellular Na+. The first discovered NHE isoform, NHE1, is expressed almost ubiquitously in all tissues, especially in the myocardium. During myocardial ische-mia-reperfusion, NHE1 catalyzes increased uptake of intracellular Na+, which in turn leads to Ca2+ overload and subsequently myocardial injury. Numerous preclinical research has shown that NHE1 is involved in cardiac hypertrophy and heart failure, but the exact molecular mecha-nisms remain elusive.
  • 330
  • 27 Sep 2022
Topic Review
Drugs Targeting Cancer Cells with Splicing Factor Mutations
Splicing factors are frequently mutated in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These mutations are presumed to contribute to oncogenic transformation, but the underlying mechanisms remain incompletely understood. While no specific treatment option is available for MDS/AML patients with spliceosome mutations, novel targeting strategies are actively explored, leading to clinical trials of small molecule inhibitors that target the spliceosome, DNA damage response pathway, and immune response pathway. 
  • 343
  • 05 Sep 2022
Topic Review
Neuroimaging-Based Assessments of OXPHOS-Related Complexes and Metabolites
In post-mortem studies, a significant dysregulation of electron transport chain (ETC) complexes was observed in patients with neurodegenerative diseases (NDs). These findings strongly implicate that mitochondrial dysfunction-linked alterations in oxidative phosphorylation (OXPHOS) can be considered a highly relevant molecular mechanism in different NDs. Histopathological examinations revealed decreased complex I level, preferentially in the substantia nigra (SN), in patients suffering from Parkinson’s disease (PD). These findings are consistent with the fact that inhibitors of complex I (such as the environmental toxins MPTP or rotenone) can cause parkinsonism in animal models and humans. Huntington’s disease (HD) has been associated with defects of complex II and, to a lesser extent, complex IV. The chronic administration of the complex II inhibitor 3-nitropropionic acid causes an HD-like phenotype in rodent and non-human primate models. In Alzheimer’s disease (AD), widespread cortical complex IV defects were identified in post-mortem brain tissue. The in vivo neuroimaging-based assessment of electron transport chain (ETC)-related metabolite levels could thus help elucidate the complex role of OXPHOS disturbances in NDs.
  • 371
  • 07 Jul 2022
Topic Review
The Biological Basis for Antioxidant Therapy
Reactive oxygen species (ROS) are a class of highly reactive free radicals, such as hydroxyl radical (•OH), the superoxide radical (O2•−) and hydrogen peroxide (H2O2). The high intracellular ROS level-induced oxidative stress leads to the upregulation of antioxidant capacity to maintain redox homeostasis by metabolic rerouting or activation of genetic programs.
  • 710
  • 06 Jul 2022
Topic Review
Sedentary Lifestyle and Masticatory Dysfunction
Unhealthy brain aging and cognitive decline associate with a sedentary lifestyle and, at a cellular level, this is accompanied by astrocyte hypertrophy, myelin dysregulation, neurovascular dysfunction and the impairment of neurogenesis.
  • 342
  • 28 Jun 2022
Topic Review
Post-Concussion Syndrome and Chronic Traumatic Encephalopathy
Traumatic brain injury is a significant public health issue and represents the main contributor to death and disability globally among all trauma-related injuries. Martial arts practitioners, military veterans, athletes, victims of physical abuse, and epileptic patients could be affected by the consequences of repetitive mild head injuries (RMHI) that do not resume only to short-termed traumatic brain injuries (TBI) effects but also to more complex and time-extended outcomes, such as post-concussive syndrome (PCS) and chronic traumatic encephalopathy (CTE). 
  • 517
  • 13 May 2022
Topic Review
The Subconjunctival Space of the Eye
The subconjunctival space is the hydrophilic, fluid-filled space between the conjunctiva and the sclera. Additionally, the subconjunctival space has access to all the blood vessels found in the conjunctiva, which can help to further distribute substances throughout the whole eye. The subconjunctival space is located superior to the cornea and optimally located to distribute drugs to several different parts of the eye through minimally invasive means while limiting the development of scar tissue.
  • 1.3K
  • 05 May 2022
Topic Review
The Intravitreal Space of the Eye
The intravitreal space comprises the majority of the eye’s volume and is located behind the lens of the eye. The vitreous chamber of the eye is mostly filled with a gel-like solution called the vitreous body. The vitreous body is 98.5–99.7% water containing salt soluble proteins and hyaluronic acid.
  • 371
  • 05 May 2022
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