Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review

To date, there is no cure or disease-modifying agents available for most well-known neurological disorders. Current therapy is typically focused on relieving symptoms and supportive care in improving the quality of life of affected patients. Furthermore, the traditional de novo drug discovery technique is more challenging, particularly for neurological disorders. Therefore, the repurposing of existing drugs for these conditions is believed to be an efficient and dynamic approach that can substantially reduce the investments spent on drug development. Currently, there is emerging evidence that suggests the potential effect of a beta-lactam antibiotic, ceftriaxone (CEF), to alleviate the symptoms of different experimentally-induced neurological disorders: Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, epileptic-seizure, brain ischemia, traumatic brain injuries, and neuropathic pain. CEF also affects the markers of oxidative status and neuroinflammation, glutamatergic systems as well as various aggregated toxic proteins involved in the pathogenesis of different neurological disorders. Moreover, it was found that CEF administration to drug dependent animal models improved the withdrawal symptoms upon drug discontinuation. Thus, this review aimed to describe the effects of CEF against multiple models of neurological illnesses, drug dependency, and withdrawal. It also emphasizes the possible mechanisms of neuroprotective actions of CEF with respective neurological maladies

Explore before you restore: Incorporating complex systems thinking in ecosystem restoration

The global movement for ecosystem restoration has gained momentum in response to the Bonn Challenge (2010) and the UN Decade on Ecosystem Restoration (UNDER, 2021–2030). While several science-based guidelines exist to aid in achieving successful restoration outcomes, significant variation remains in the outcomes of restoration projects. Some of this disparity can be attributed to unexpected responses of ecosystem components to planned interventions.Given the complex nature of ecosystems, we propose that concepts from Complex Systems Science (CSS) that are linked to non-linearity, such as regime shifts, ecological resilience and ecological feedbacks, should be employed to help explain this variation in restoration outcomes from an ecological perspective.Our framework, Explore Before You Restore, illustrates how these concepts impact restoration outcomes by influencing degradation and recovery trajectories. Additionally, we propose incorporating CSS concepts into the typical restoration project cycle through a CSS assessment phase and suggest that the need for such assessment is explicitly included in the guidelines to improve restoration outcomes.To facilitate this inclusion and make it workable by practitioners, we describe indicators and methods available for restoration teams to answer key questions that should make up such CSS assessment. In doing so, we identify key outstanding science and policy tasks that are needed to further operationalize CSS assessment in restoration.Synthesis and applications. By illustrating how key Complex Systems Science (CSS) concepts linked to non-linear threshold behaviour can impact restoration outcomes through influencing recovery trajectories, our framework Explore Before You Restore demonstrates the need to incorporate Complex Systems thinking in ecosystem restoration. We argue that inclusion of CSS assessment into restoration project cycles, and more broadly, into international restoration guidelines, may significantly improve restoration outcomes

Explore before you restore: Incorporating complex systems thinking in ecosystem restoration

Abstract The global movement for ecosystem restoration has gained momentum in response to the Bonn Challenge (2010) and the UN Decade on Ecosystem Restoration (UNDER, 2021–2030). While several science‐based guidelines exist to aid in achieving successful restoration outcomes, significant variation remains in the outcomes of restoration projects. Some of this disparity can be attributed to unexpected responses of ecosystem components to planned interventions. Given the complex nature of ecosystems, we propose that concepts from Complex Systems Science (CSS) that are linked to non‐linearity, such as regime shifts, ecological resilience and ecological feedbacks, should be employed to help explain this variation in restoration outcomes from an ecological perspective. Our framework, Explore Before You Restore, illustrates how these concepts impact restoration outcomes by influencing degradation and recovery trajectories. Additionally, we propose incorporating CSS concepts into the typical restoration project cycle through a CSS assessment phase and suggest that the need for such assessment is explicitly included in the guidelines to improve restoration outcomes. To facilitate this inclusion and make it workable by practitioners, we describe indicators and methods available for restoration teams to answer key questions that should make up such CSS assessment. In doing so, we identify key outstanding science and policy tasks that are needed to further operationalize CSS assessment in restoration. Synthesis and applications. By illustrating how key Complex Systems Science (CSS) concepts linked to non‐linear threshold behaviour can impact restoration outcomes through influencing recovery trajectories, our framework Explore Before You Restore demonstrates the need to incorporate Complex Systems thinking in ecosystem restoration. We argue that inclusion of CSS assessment into restoration project cycles, and more broadly, into international restoration guidelines, may significantly improve restoration outcomes. </jats:p

Netrin as a Novel Biomarker and Its Therapeutic Implications in Diabetes Mellitus and Diabetes-Associated Complications

Diabetes is a multifactorial metabolic syndrome and is one of the shared long-lasting illnesses globally. It is linked to long-term microvascular and macrovascular complications that contribute to disability, compromised quality of life, and reduction in lifespan, which eventually leads to death. This disease is not only incurring significant economic burden but also adversely affects the patients, caregivers, communities, and the society at large. The interruption of diabetes progress and its complications is a primary focus of scientific communities. In spite of various diagnostic modalities for diabetes, there is a limited marker to investigate the risk and progress of its complications. Netrin has recently received more attention as a biomarker of diabetes and a broader range of long-term complication. Therefore, the impetus of this review is to exhaustively discuss the role of Netrin as a potential biomarker and its therapeutic implication in diabetes and diverse sets of microvascular and macrovascular complications of diabetes. It also discourses the possible mechanisms of Netrin for the said pharmacological effect for a better understanding of the development and progression of diabetes and its complications in relation to this protein. It enables protective measures to be applied at the subclinical stage and the responses to preventive or therapeutic measures to be scrutinized. Besides, it might also facilitate the appraisal of novel therapeutic options for diabetes and various complications through modifying the endogenous Netrin and provide surrogate endpoints for intervention