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Nature Reviews. Neurology Sep 2023Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that is classically thought to impact the motor system. Over the past 20 years, research has... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease that is classically thought to impact the motor system. Over the past 20 years, research has started to consider the contribution of non-motor symptoms and features of the disease, and how they might affect ALS prognosis. Of the non-motor features of the disease, nutritional status (for example, malnutrition) and metabolic balance (for example, weight loss and hypermetabolism) have been consistently shown to contribute to more rapid disease progression and/or earlier death. Several complex cellular changes observed in ALS, including mitochondrial dysfunction, are also starting to be shown to contribute to bioenergetic failure. The resulting energy depletion in high energy demanding neurons makes them sensitive to apoptosis. Given that nutritional and metabolic stressors at the whole-body and cellular level can impact the capacity to maintain optimal function, these factors present avenues through which we can identify novel targets for treatment in ALS. Several clinical trials are now underway evaluating the effectiveness of modifying energy balance in ALS, making this article timely in reviewing the evidence base for metabolic and nutritional interventions.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Energy Metabolism; Prognosis; Disease Progression
PubMed: 37500993
DOI: 10.1038/s41582-023-00845-8 -
Expert Review of Clinical Immunology Apr 2024Metabolic-associated liver diseases have emerged pandemically across the globe and are clinically related to metabolic disorders such as obesity and type 2 diabetes. The... (Review)
Review
INTRODUCTION
Metabolic-associated liver diseases have emerged pandemically across the globe and are clinically related to metabolic disorders such as obesity and type 2 diabetes. The new nomenclature and definition (i.e. metabolic dysfunction-associated steatotic liver disease - MASLD; metabolic dysfunction-associated steatohepatitis - MASH) reflect the nature of these complex systemic disorders, which are characterized by inflammation, gut dysbiosis and metabolic dysregulation. In this review, we summarize recent advantages in understanding the pathophysiology of MASLD, which we parallel to emerging therapeutic concepts.
AREAS COVERED
We summarize the pathophysiologic concepts of MASLD and its transition to MASH and subsequent advanced sequelae of diseases. Furthermore, we highlight how dietary constituents, microbes and associated metabolites, metabolic perturbations, and immune dysregulation fuel lipotoxicity, hepatic inflammation, liver injury, insulin resistance, and systemic inflammation. Deciphering the intricate pathophysiologic processes that contribute to the development and progression of MASLD is essential to develop targeted therapeutic approaches to combat this escalating burden for health-care systems.
EXPERT OPINION
The rapidly increasing prevalence of metabolic dysfunction-associated steatotic liver disease challenges health-care systems worldwide. Understanding pathophysiologic traits is crucial to improve the prevention and treatment of this disorder and to slow progression into advanced sequelae such as cirrhosis and hepatocellular carcinoma.
Topics: Humans; Diabetes Mellitus, Type 2; Liver Cirrhosis; Disease Progression; Inflammation; Liver Neoplasms
PubMed: 38149354
DOI: 10.1080/1744666X.2023.2294046 -
Frontiers in Immunology 2023C-reactive protein (CRP) is well-recognized as a sensitive biomarker of inflammation. Association of elevations in plasma/serum CRP level with disease state has received... (Review)
Review
C-reactive protein (CRP) is well-recognized as a sensitive biomarker of inflammation. Association of elevations in plasma/serum CRP level with disease state has received considerable attention, even though CRP is not a specific indicator of a single disease state. Circulating CRP levels have been monitored with a varying degree of success to gauge disease severity or to predict disease progression and outcome. Elevations in CRP level have been implicated as a useful marker to identify patients at risk for cardiovascular disease and certain cancers, and to guide therapy in a context-dependent manner. Since even strong associations do not establish causality, the pathogenic role of CRP has often been over-interpreted. CRP functions as an important modulator of host defense against bacterial infection, tissue injury and autoimmunity. CRP exists in conformationally distinct forms, which exhibit distinct functional properties and help explaining the diverse, often contradictory effects attributed to CRP. In particular, dissociation of native pentameric CRP into its subunits, monomeric CRP, unmasks "hidden" pro-inflammatory activities in pentameric CRP. Here, we review recent advances in CRP targeting strategies, therapeutic lowering of circulating CRP level and development of CRP antagonists, and a conformation change inhibitor in particular. We will also discuss their therapeutic potential in mitigating the deleterious actions attributed to CRP under various pathologies, including cardiovascular, pulmonary and autoimmune diseases and cancer.
Topics: Humans; C-Reactive Protein; Inflammation; Biomarkers; Cardiovascular Diseases; Disease Progression
PubMed: 37564640
DOI: 10.3389/fimmu.2023.1237729 -
Nature Immunology Dec 2023Visualization of the cellular heterogeneity and spatial architecture of the tumor microenvironment (TME) is becoming increasingly important to understand mechanisms of... (Review)
Review
Visualization of the cellular heterogeneity and spatial architecture of the tumor microenvironment (TME) is becoming increasingly important to understand mechanisms of disease progression and therapeutic response. This is particularly relevant in the era of cancer immunotherapy, in which the contexture of immune cell positioning within the tumor landscape has been proven to affect efficacy. Although single-cell technologies have mostly replaced conventional approaches to analyze specific cellular subsets within tumors, those that integrate a spatial dimension are now on the rise. In this Review, we assess the strengths and limitations of emerging spatial technologies with a focus on their applications in tumor immunology, as well as forthcoming opportunities for artificial intelligence (AI) and the value of integrating multiomics datasets to achieve a holistic picture of the TME.
Topics: Humans; Tumor Microenvironment; Artificial Intelligence; Disease Progression; Immunotherapy; Neoplasms
PubMed: 38012408
DOI: 10.1038/s41590-023-01678-9 -
Journal of Neurology Dec 2023In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache... (Review)
Review
BACKGROUND
In individuals with migraine, attacks may increase in frequency, severity, or both. Preventing migraine progression has emerged as a treatment goal in headache subspecialty practice, but there may be less awareness in general neurology or primary care settings where most people with migraine who seek treatment consult. Herein, we review the definition of and risk factors for migraine progression and consider strategies that could reduce its risk.
METHODS
A group of headache expert healthcare professionals, clinicians, and researchers reviewed published evidence documenting factors associated with increased or decreased rates of migraine progression and established expert opinions for disease management recommendations. Strength of evidence was rated as good, moderate, or based solely on expert opinion, using modified criteria for causation developed by AB Hill.
RESULTS
Migraine progression is commonly operationally defined as the transition from ≤ 15 to ≥ 15 monthly headache days among people with migraine; however, this does not necessarily constitute a fundamental change in migraine biology and other definitions should be considered. Established and theoretical key risk factors for migraine progression were categorized into five domains: migraine disease characteristics, treatment-related factors, comorbidities, lifestyle/exogenous factors, and demographic factors. Within these domains, good evidence supports the following risk factors: poorly optimized acute headache treatment, cutaneous allodynia, acute medication overuse, selected psychiatric symptoms, extra-cephalic chronic pain conditions, metabolism-related comorbidities, sleep disturbances, respiratory conditions, former/current high caffeine intake, physical inactivity, financial constraints, tobacco use, and personal triggers as risk factors. Protective actions that may mitigate migraine progression are sparsely investigated in published literature; our discussion of these factors is primarily based on expert opinion.
CONCLUSIONS
Recognizing risk factors for migraine progression will allow healthcare providers to suggest protective actions against migraine progression (Supplementary Fig. 1). Intervention studies are needed to weight the risk factors and test the clinical benefit of hypothesized mitigation strategies that emerge from epidemiological evidence.
Topics: Humans; Migraine Disorders; Chronic Disease; Risk Factors; Headache; Disease Progression; Patient-Centered Care
PubMed: 37615752
DOI: 10.1007/s00415-023-11880-2 -
Journal of Physiology and Biochemistry Nov 2023Metabolic dysfunction-associated fatty liver disease (MAFLD) is nowadays considered the liver manifestation of metabolic syndrome. Its prevalence is increasing worldwide... (Review)
Review
Metabolic dysfunction-associated fatty liver disease (MAFLD) is nowadays considered the liver manifestation of metabolic syndrome. Its prevalence is increasing worldwide in parallel to the epidemic of diabetes and obesity. MAFLD includes a wide spectrum of liver injury including simple steatosis and non-alcoholic steatohepatitis (NASH) that may lead to serious complications such as liver cirrhosis and liver cancer. The complexity of its pathophysiology and the intricate mechanisms underlying disease progression explains the huge variety of molecules targeting diverse biological mechanisms that have been tested in preclinical and clinical settings in the last two decades. Thanks to the large number of clinical trials of the last few years, most of them still ongoing, the pharmacotherapy scenario of MAFLD is rapidly evolving. The three major components of MAFLD, steatosis, inflammation, and fibrosis seem to be safely targeted with different agents at least in a large proportion of patients. Likely, in the next few years more than one drug will be approved for the treatment of MAFLD at different disease stages. The aim of this review is to synthesize the characteristics and the results of the most advanced clinical trials for the treatment of NASH to evaluate the recent advances of pharmacotherapy in this disease.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Disease Progression; Inflammation; Liver Cirrhosis
PubMed: 36976456
DOI: 10.1007/s13105-023-00954-4 -
Continuum (Minneapolis, Minn.) Feb 2024Immune-mediated myelopathies are conditions in which the immune system attacks the spinal cord. This article describes the distinguishing characteristics of...
OBJECTIVE
Immune-mediated myelopathies are conditions in which the immune system attacks the spinal cord. This article describes the distinguishing characteristics of immune-mediated myelopathies and treatment strategies for patients affected by these disorders.
LATEST DEVELOPMENTS
New biomarkers, such as aquaporin 4 and myelin oligodendrocyte glycoprotein antibodies, in the blood and spinal fluid have led to the identification of antigen-specific immune-mediated myelopathies and approved therapies to prevent disease progression.
ESSENTIAL POINTS
The first step in the diagnosis of an immune-mediated myelopathy is confirming that the immune system is the cause of the attack by excluding non-immune-mediated causes. The second step is to narrow the differential diagnosis based on objective biomarkers such as serology and MRI patterns. The third step is to treat the specific immune-mediated myelopathy by using evidence-based medicine.
Topics: Humans; Spinal Cord Diseases; Aquaporin 4; Disease Progression; Biomarkers
PubMed: 38330478
DOI: 10.1212/CON.0000000000001382 -
The AAPS Journal Aug 2023Macrophages, as one of the most abundant tumor-infiltrating cells, play an important role in tumor development and metastasis. The frequency and polarization of... (Review)
Review
Macrophages, as one of the most abundant tumor-infiltrating cells, play an important role in tumor development and metastasis. The frequency and polarization of tumor-associated macrophages (TAMs) correlate with disease progression, tumor metastasis, and resistance to various treatments. Pro-inflammatory M1 macrophages hold the potential to engulf tumor cells. In contrast, anti-inflammatory M2 macrophages, which are predominantly present in tumors, potentiate tumor progression and immune escape. Targeting macrophages to modulate the tumor immune microenvironment can ameliorate the tumor-associated immunosuppression and elicit an anti-tumor immune response. Strategies to repolarize TAMs, deplete TAMs, and block inhibitory signaling hold great potential in tumor therapy. Besides, biomimetic carriers based on macrophages have been extensively explored to prolong circulation, enhance tumor-targeted delivery, and reduce the immunogenicity of therapeutics to augment therapeutic efficacy. Moreover, the genetic engineering of macrophages with chimeric antigen receptor (CAR) allows them to recognize tumor antigens and perform tumor cell-specific phagocytosis. These strategies will expand the toolkit for treating tumors, especially for solid tumors, drug-resistant tumors, and metastatic tumors. Herein, we introduce the role of macrophages in tumor progression, summarize the recent advances in macrophage-centered anticancer therapy, and discuss their challenges as well as future applications. Graphical abstract.
Topics: Humans; Macrophages; Biomimetics; Disease Progression; Genetic Engineering
PubMed: 37589825
DOI: 10.1208/s12248-023-00845-y -
Ugeskrift For Laeger Nov 2023The prevalence of myopia is estimated to be 2.6 billion people worldwide and the percentage of individuals with sight-threatening high myopia (≤ -6 diopters) is... (Review)
Review
The prevalence of myopia is estimated to be 2.6 billion people worldwide and the percentage of individuals with sight-threatening high myopia (≤ -6 diopters) is increasing. Myopia is primarily caused by excessive axial elongation of the eyeball, and treatment modalities attempt to reduce this progression. While increased outdoor time is known to delay myopia onset, new pharmacological and optical interventions aim to reduce myopia progression. This review finds that these promising interventions are expected to significantly decrease the future prevalence of sight-threatening high myopia.
Topics: Child; Humans; Adolescent; Disease Progression; Myopia; Prevalence
PubMed: 38018731
DOI: No ID Found -
International Journal of Molecular... Sep 2023Kidney disease is a major global health concern, affecting millions of people. Nephrologists have shown interest in platelets because of coagulation disorders caused by... (Review)
Review
Kidney disease is a major global health concern, affecting millions of people. Nephrologists have shown interest in platelets because of coagulation disorders caused by renal diseases. With a better understanding of platelets, it has been found that these anucleate and abundant blood cells not only play a role in hemostasis, but also have important functions in inflammation and immunity. Platelets are not only affected by kidney disease, but may also contribute to kidney disease progression by mediating inflammation and immune effects. This review summarizes the current evidence regarding platelet abnormalities in renal disease, and the multiple effects of platelets on kidney disease progression. The relationship between platelets and kidney disease is still being explored, and further research can provide mechanistic insights into the relationship between thrombosis, bleeding, and inflammation related to kidney disease, and elucidate targeted therapies for patients with kidney disease.
Topics: Humans; Immunity, Innate; Blood Platelets; Hemostasis; Inflammation; Kidney Diseases; Disease Progression
PubMed: 37834171
DOI: 10.3390/ijms241914724