查看更多>>摘要：Type 2 Diabetes Mellitus (T2D) is a chronic disease with a pandemic incidence whose pathogenesis has not yet been clarified. Raising evidence highlighted the role of oxidative stress in inducing insulin resistance, pancreatic beta-cell dysfunction, and leading to cardiovascular disease (CVD). Therefore, understanding the link between oxidative stress, T2D and CVD may help to further understand the pathological processes beyond this association, to personalize the algorithm of the cure, and to find new therapeutic targets. Here, we discussed the role of oxidative stress and the decrease of antioxidant defenses in the pathogenesis of T2D. Furthermore, some aspects of hypoglycemic therapies and their potential role as antioxidant agents were examined, which might be pivotal in preventing CVD in T2D patients.
查看更多>>摘要：Neurodegenerative diseases (NDDs) are a range of neurological disorders featured by neuronal degeneration and apoptosis. Cellular Calcium (Ca2+) and reactive oxygen species (ROS) dyshomeostasis are the earliest and important events in the development of NDDs and may yield promising therapeutic targets for NDDs. Paeoniflorin, a water-soluble monoterpene glucoside, is the major bioactive monomer extracted from the root of Paeonia lactiflora pall. Increasing evidence has suggested that this natural compound might be used to treat various NDDs, and its potential molecular mechanisms are related to the modulation of Ca2+/ROS homeostasis in cells. In addition, paeoniflorin accounts for more than 40% of the total glucosides of herbaceous peonies with abundant herbaceous sources. Furthermore, it has also been validated as a safe extraction in clinical pharmacological research with a wide therapeutic window. Hence, it is rational to anticipate paeoniflorin being a promising candidate for the treatment of NDDs via regulating Ca2+/ROS dyshomeostasis.
查看更多>>摘要：Microglia and CNS-infiltrating macrophages play significant roles in the pathogenesis of neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Prolonged and dysregulated inflammatory responses by these innate immune cells can have deleterious effects on the surrounding CNS microenvironment, which can worsen neurodegeneration and demyelination. However, although chronic activation of proinflammatory microglia is maladaptive, other functional microglial subtypes play beneficial roles during CNS repair and regeneration. Therefore, there is a tremendous interest in understanding the underlying mechanism of the activation of these reparative/regenerative microglia. In this review, we focus on the potential role of PKC, a downstream signaling molecule of TREM2 and PLC gamma 2, and PKC modulators in promoting the activation of reparative/regenerative microglial subtypes as a novel therapy for neuroinflammatory and neurodegenerative diseases.
Peverini, LaurieDunning, KatePeralta, Francisco AndresGrutter, Thomas...
8页
查看更多>>摘要：Ligand-gated ion channels (LGIC, also referred to as ionotropic receptors) are important transmembrane proteins that open to allow ions to flow across the membrane and locally modify the membrane potential in response to the binding of a ligand. For more than a decade, a tremendous effort has been carried out in the determination of many LGIC structures in high resolution, leading to an unprecedented molecular description of channel gating. However, it is sometimes difficult to classify experimentally derived structures to their corresponding functional states, and alternative methods may help resolve or refine this issue. In this review, we focus on the application of photo-isomerizable tweezers (PIT) as a powerful strategy to interrogate molecular mechanisms of LGIC while assessing their functionality by electrophysiology.
Alganem, KhaledHamoud, Abdul-RizaqCreeden, Justin F.Henkel, Nicholas D....
13页
查看更多>>摘要：Biological regulatory networks are dynamic, intertwined, and complex systems making them challenging to study. While quantitative measurements of transcripts and proteins are key to investigate the state of a biological system, they do not inform the "active" state of regulatory networks. In consideration of that fact, "functional" proteomics assessments are needed to decipher active regulatory processes. Phosphorylation, a key posttranslation modification, is a reversible regulatory mechanism that controls the functional state of proteins. Recent advancements of high-throughput protein kinase activity profiling platforms allow for a broad assessment of protein kinase networks in complex biological systems. In conjunction with sophisticated computational modeling techniques, these profiling platforms provide datasets that inform the active state of regulatory systems in disease models and highlight potential drug targets. Taken together, system-wide profiling of protein kinase activity has become a critical component of modern molecular biology research and presents a promising avenue for drug discovery.
查看更多>>摘要：Injury in the central nervous system leads to neurological deficits, depending on the disruption of neural networks. Remyelination, which occurs partially and spontaneously, is a critical process in the regeneration of neural networks to recover from neurological deficits. Remyelination depends on the development of oligodendrocytes, including the proliferation of oligodendrocyte precursor cells (OPCs) and the differentiation of OPCs into mature oligodendrocytes to form myelin. OPC proliferation and differentiation are regulated by intracellular and extracellular mechanisms, and recent studies have demonstrated that circulating factors secreted from peripheral organs or infiltrated immune cells play a key role in controlling oligodendrocyte development following remyelination in adult mammals. In this review, we describe the beneficial and detrimental effects of systemic environments, such as circulating factors derived from peripheral organs and immune cells, on CNS remyelination.
查看更多>>摘要：Glaucoma is a leading cause of blindness worldwide. Although intraocular pressure is the main risk factor for glaucoma, several intraocular pressure independent factors have been associated with the risk of developing the disease and its progression. The diagnosis of glaucoma relies on clinical features of the optic nerve, visual field test, and optical coherence tomography. However, the multidisciplinary aspect of the disease suggests that other biomarkers may be useful for the diagnosis, thus underling the importance of novel imaging techniques supporting clinicians. This review analyzes the common pathogenic mechanisms between glaucoma and Alzheimer's disease and the possible novel approaches for diagnosis and follow up.
查看更多>>摘要：Alcohol contributes to more than 5% of global mortality, and causes more than half of all liver-related deaths. The Alcohol Use Disorders Identification Test (AUDIT) can be used to detect those patients with hazardous drinking and alcohol dependence who will benefit from psychosocial and pharmacological alcohol treatment. Psychosocial treatments range from brief interventions and cognitive behavioral therapy, to experimental neuropsychological treatments. Psychosocial intervention can be combined with acamprosate or naltrexone as first line pharmacological treatments. For patients with liver disease, abstinence increases survival and is therefore an important treatment goal. Acamprosate is a good choice, as it prevents relapse to drinking with a number needed to treat of 12. There are no reports indicating high risks of liver toxicity for acamprosate or naltrexone, but evidence is scarce. We recommend vigorous screening for alcohol use disorder in liver disease patients, followed by psychosocial intervention and complemented by pharmaceutical therapy.
查看更多>>摘要：The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has hit every corner of the world faster than any infectious disease ever known. In this context, rapid and accurate testing of positive cases are essential to follow the test-trace-isolate strategy (TETRIS), which has proven to be a key approach to constrain viral spread. Here, we discuss how to interpret and combine molecular or/and antigen-based detection methods for SARS-CoV-2 as well as when they should be used. Their application can be cleverly designed as an algorithm to prevent viral dissemination according to distinct epidemiological contexts within surveillance programs.
NSTL
Elsevier