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Trends in Cell Biology Jun 2020Cell death is an essential feature of development in multicellular organisms, a critical driver of degenerative diseases, and can be harnessed for treating some cancers.... (Review)
Review
Cell death is an essential feature of development in multicellular organisms, a critical driver of degenerative diseases, and can be harnessed for treating some cancers. Understanding the mechanisms governing cell death is critical for addressing its role in disease. Similarly, metabolism is essential for normal energy and biomolecule production, and goes awry in many diseases. Metabolism and cell death are tightly linked in the phenomenon of ferroptosis, a form of regulated cell death driven by peroxidation of phospholipids. Glutathione peroxidase 4 (GPX4) uses glutathione to protect cells from ferroptosis by eliminating phospholipid peroxides. Recent data have revealed glutathione/GPX4-independent axes for suppressing ferroptosis, and insight into the regulation of iron and mitochondria in ferroptosis. Ferroptosis has recently been implicated in multiple diseases, and functions as a tumor suppression mechanism. Ferroptosis induction is a promising approach in treating several conditions, including neoplastic diseases. Here, we summarize these recent advances.
Topics: Animals; Disease; Ferroptosis; Humans; Iron; Lipid Peroxides; Metabolic Networks and Pathways; Neoplasms
PubMed: 32413317
DOI: 10.1016/j.tcb.2020.02.009 -
Nature Jun 2023Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate... (Review)
Review
Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesis-establishing stable spatial and functional relationships with specialized tissue cells-and persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.
Topics: Animals; Humans; Cell Differentiation; Cell Lineage; Hematopoietic Stem Cells; Macrophages; Microglia; Monocytes; Organ Specificity; Disease
PubMed: 37344646
DOI: 10.1038/s41586-023-06002-x -
JPMA. the Journal of the Pakistan... Mar 2022Augmentative and Alternative Communication is an aided or unaided means of communication which supports existing communication abilities of an individual or replaces... (Review)
Review
Augmentative and Alternative Communication is an aided or unaided means of communication which supports existing communication abilities of an individual or replaces natural speech due to any speech and language disorder. The deficit could be developmental or acquired such as autism spectrum disorder, cerebral palsy, learning difficulties, dysarthria, dyspraxia or due to any acquired neurological condition such as aphasia and other degenerative disorders. Furthermore, it may be due to surgical procedures such as laryngectomy. Alternate means of communication have also been successfully used with COVID-19 patients. These tools may include pictures, symbols, signs or voice output devices. Parents of children with special needs and medical professionals have been reluctant in implementing the approach due to certain misconceptions. The aim of this review is to summarize the current evidence for the use of Augmentative and Alternative Communication with a range of disorders in relation to in relation to Pakistan.
Topics: Autism Spectrum Disorder; COVID-19; Child; Communication; Communication Aids for Disabled; Communication Disorders; Humans; Language Therapy; Pakistan; Speech; Speech Therapy
PubMed: 35320253
DOI: 10.47391/JPMA.22-023 -
Neurotherapeutics : the Journal of the... Oct 2018Inclusion body myositis is the most common acquired myopathy after the age of 50. It is characterized by progressive asymmetric weakness predominantly affecting the... (Review)
Review
Inclusion body myositis is the most common acquired myopathy after the age of 50. It is characterized by progressive asymmetric weakness predominantly affecting the quadriceps and/or finger flexors. Loss of ambulation and dysphagia are major complications of the disease. Inclusion body myositis can be associated with cytosolic 5'-nucleotidase 1A antibodies. Muscle biopsy usually shows inflammatory cells surrounding and invading non-necrotic muscle fibers, rimmed vacuoles, congophilic inclusions, and protein aggregates. Disease pathogenesis remains poorly understood and consists of an interplay between inflammatory and degenerative pathways. Antigen-driven, clonally restricted, cytotoxic T cells represent a main feature of the inflammatory component, whereas abnormal protein homeostasis with protein misfolding, aggregation, and dysfunctional protein disposal is the hallmark of the degenerative component. Inclusion body myositis remains refractory to treatment. Better understanding of the disease pathogenesis led to the identification of novel therapeutic targets, addressing both the inflammatory and degenerative pathways.
Topics: Animals; Humans; Muscle, Skeletal; Myositis, Inclusion Body
PubMed: 30136253
DOI: 10.1007/s13311-018-0658-8 -
Continuum (Minneapolis, Minn.) Feb 2019This article reviews two of the primary progressive aphasias (PPAs), disorders characterized by the early and predominant impairment of language, and primary progressive... (Review)
Review
PURPOSE OF REVIEW
This article reviews two of the primary progressive aphasias (PPAs), disorders characterized by the early and predominant impairment of language, and primary progressive apraxia of speech, a degenerative motor speech disorder that is closely related to PPA. An outline of the history and controversy surrounding how these disorders are classified is provided before the article focuses on each disorder's clinical and imaging features.
RECENT FINDINGS
Over the past decade, the classification of degenerative speech and language disorders has been refined. Clinical, imaging, and pathologic evidence suggests that primary progressive apraxia of speech is a distinct degenerative disorder. Furthermore, multiple lines of evidence have highlighted issues with nonfluent/agrammatic variant PPA, which complicates the diagnosis, prognosis, and study of this disorder. Semantic variant PPA, while not without controversy, remains one of the most well-defined disorders, with good clinicopathologic correlation.
SUMMARY
Accurate classification and diagnosis of these degenerative speech and language disorders is crucial in clinical practice and ongoing research efforts. For nonfluent/agrammatic variant PPA, the authors suggest emphasizing agrammatism as the core inclusion criterion and taking care not to include patients with isolated or predominant apraxia of speech. Isolated apraxia of speech can be the manifestation of a degenerative disease and, based on the different prognosis, should be recognized as distinct from PPA. Finally, it is important to recognize that some patients with semantic dementia, despite sharing the same pathologic associations, may not meet criteria for PPA.
Topics: Aged; Aphasia, Primary Progressive; Apraxias; Brain; Female; Fluorodeoxyglucose F18; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Neurologic Examination; Neuropsychological Tests; Positron-Emission Tomography; Speech
PubMed: 30707189
DOI: 10.1212/CON.0000000000000699 -
Mitochondrion May 2014The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical,... (Review)
Review
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.
Topics: Brain; Disease; Energy Metabolism; Health; Homeostasis; Humans; Metabolic Networks and Pathways; Mitochondria; Stress, Physiological
PubMed: 23981537
DOI: 10.1016/j.mito.2013.08.006 -
Cells Apr 2019Parkinson's disease (PD) is the second most common degenerative disorder. Although the disease was described more than 200 years ago, its pathogenetic mechanisms have... (Review)
Review
Parkinson's disease (PD) is the second most common degenerative disorder. Although the disease was described more than 200 years ago, its pathogenetic mechanisms have not yet been fully described. In recent years, the discovery of the association between mutations of the gene (encoding for the lysosomal enzyme glucocerebrosidase) and PD facilitated a better understating of this disorder. mutations are the most common genetic risk factor of the disease. However, mutations of this gene can be found in different phenotypes, such as Gaucher's disease (GD), PD, dementia with Lewy bodies (DLB) and rapid eye movements (REM) sleep behavior disorders (RBDs). Understanding the pathogenic role of this mutation and its different manifestations is crucial for geneticists and scientists to guide their research and to select proper cohorts of patients. Moreover, knowing the implications of the mutation in the context of PD and the other associated phenotypes is also important for clinicians to properly counsel their patients and to implement their care. With the present review we aim to describe the genetic, clinical, and therapeutic features related to the mutation of the gene.
Topics: Gaucher Disease; Glucosylceramidase; Humans; Lewy Body Disease; Mutation; Parkinson Disease; Phenotype; Risk Factors
PubMed: 31010158
DOI: 10.3390/cells8040364 -
Journal of Back and Musculoskeletal... 2022Low back pain is a significant spinal disorder that affects much of the population at some point during their lives. (Review)
Review
BACKGROUND
Low back pain is a significant spinal disorder that affects much of the population at some point during their lives.
OBJECTIVE
While proper diagnosis is key, diagnosing the underlying cause of low back pain may often be unclear.
METHOD
In this review article, we discuss lumbar instability as an etiology of low back pain and its treatment by prolotherapy.
RESULTS
Spinal ligaments may be an underlying culprit in the development of lumbar instability with resultant low back pain and associated disorders.
CONCLUSION
In these cases, adequate treatment consisting of non-biologic prolotherapy or cellular prolotherapy, including platelet rich plasma (PRP), can be beneficial in restoring spinal stability and resolving chronic low back pain.
Topics: Humans; Joint Instability; Low Back Pain; Lumbar Vertebrae; Platelet-Rich Plasma; Prolotherapy; Spinal Diseases
PubMed: 34957989
DOI: 10.3233/BMR-210097 -
Orphanet Journal of Rare Diseases Oct 2006Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus... (Review)
Review
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).
Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Metabolic Diseases; Nervous System Diseases; Night Blindness; Pregnancy; Prenatal Diagnosis; Prognosis; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Rhodopsin; Sensation Disorders; Syndrome
PubMed: 17032466
DOI: 10.1186/1750-1172-1-40 -
BBA Clinical Dec 2016Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is... (Review)
Review
Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer's and Parkinson's), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or "brain caps". This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.
PubMed: 27752476
DOI: 10.1016/j.bbacli.2016.09.002