Osseous Rosai-Dorfman disease of tibia in children:A case report

BACKGROUND Rosai-Dorfman disease(RDD),or sinus histiocytosis with massive lymphadenopathy,is a benign histiocytic disorder.Extranodal involvement is common,occurring in>40%of patients,but bone involvement occurs in<10%of cases.In addition,primary bone RDD is extremely rare.The majority of patients are adolescents and young adults,and the mean age at onset is 20-years-old.CASE SUMMARY We report an 8-year-old Chinese girl who presented to our hospital with an insidious onset of swelling and pain in the middle shaft of her right tibia for 4 mo.We performed total surgical resection of the right tibia lesion and allograft transplantation.A good prognosis was confirmed at the 6 mo follow-up.Pain and swelling symptoms were totally relieved,range of motion of her right knee and ankle returned to normal,and there was no clinical evidence of lesion recurrence at last follow up.Our case is the second reported case of osseous RDD without lymphadenopathy in the shaft of the tibia of a child.CONCLUSION Extranodal RDD is a rare disease and can be misdiagnosed easily.Lesion resection and allograft transplantation are an option to treat extranodal RDD in children with good short term result.Pediatric orthopedist should be aware of this rare disease,especially extranodal involvement.

Rosai-Dorfman disease with lung involvement in a 10-year-old patient:A case report

BACKGROUND Rosai-Dorfman disease(RDD)is a rare benign proliferative disease whose etiology is not clear and may be related to infection or unexplained immune dysfunction.The authors present a case of RDD with lung involvement in a 10-year-old patient.CASE SUMMARY A 10-year-old girl found that her left cervical lymph nodes were enlarged for more than 7 mo,and the largest range was about 6.5 cm×5.9 cm×8.1 cm.Cervical magnetic resonance imaging showed multiple masses in the left neck,with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.A malignant tumor,with a high possibility of lymph node metastasis,was initially considered.At the same time,lung computed tomography showed multiple nodules of different sizes scattered on both sides of the lung,with uniform internal density.Thus,a possible metastatic tumor was considered.Finally,RDD was diagnosed by pathology and immunohistochemistry.According to the antibiogram,clindamycin was administered for 2 wk,and prednisone acetate was administered for 7 wk.Nine months later,the ulcer in the left neck was better than before,but the imaging showed that the lesion was not controlled.CONCLUSION The diagnosis of RDD cannot be made by a single tool and its treatment is a longterm exploratory process.Follow-up is necessary.

Rosai-Dorfman Disease: Two Cases Report and Literature Review

The lymph node is the revelation mode of several pathology. In tropical area, their etiology are dominated by tuberculosis and hemopathy. Some etiology such as histiocytosis are rarely mentioned. We report two cases of Rosai-Dorfman-Destombes disease. The first observation concerned a patient of 45 years without pathological antecedent, who had a inguinal and cervical tumoral lymph nodes. This evolved in a feverish poor general condition. Infection research was negative. Morphological explorations found deep lymph nodes. The excision biopsy examination concluded to Rosai-Dorfman-Destombes disease. The second observation concerned a patient of 40 years without pathological antecedent, who had a chronic non-inflammatory left supra-collarbone lymph node, associated with poor general condition and fever. X-ray showed mediastinal lymph nodes and ultra-sonography showed mesenteric lymph nodes, and latero-aortic lymph nodes. The examination of the excision biopsy was for Rosai Dorfman Destombes disease. The difficulty of diagnosis in our regions based on technical tray lack and our patients financial limits. Also this disease is rarely mentioned first. This is often the source of considerable diagnostic delay noted in our two patients and therefore the initiation of an untimely anti-tuberculosis treatment.

Incidental Finding of Isolated Rosai-Dorfman Disease in the Tonsils of a 4-Year-Old Girl: A Case Report and a Brief Review of Current Practice in Tonsillectomy Specimen Handling

We report herein a case of isolated Rosai-Dorfman disease (Sinus Histiocytosis with Massive Lymphadenopathy) diagnosed upon routine microscopic examination of tonsils in a child. The patient is a 4 year old girl who had a history of sleep apnea, but no other significant medical history or other findings on physical examination. In this report, we discuss the various approaches to handling of tonsillectomy specimens. We also discuss the value of routine microscopic examination, providing a list of case examples of incidental, clinically important, findings that can be missed if a microscopic examination of tonsils was not performed. We finally discuss the clinical significance of finding histologic evidence of Rosai-Dorfman disease in a child.

The Destombes-Rosai-Dorfman Disease or Sinus Histiocytosis with Massive Lymphadenopathy: A Rare Case Described in the Paediatrics Department of Yalgado Ouedraogo University Hospital

Destombes-Rosai-Dorfman’ disease (DRD) is an inflammatory non-langerhansian histiocytosis with adenomegaly. It is a rare histiocytic disorder worldwide, less than 1000 reported cases. It is of unknown etiology and is characterized in its classical form by multiple adenomegalia, especially localized at cervical area, but also at mediastinal, axillary and inguinal areas. It is a benign condition, even if it is deforming, with spontaneously resolving evolution. We report a case of DRD disease in a 13-year-old girl, hospitalized in the Department of Pediatrics of the Yalgado Ouédraogo University Hospital Center in Ouagadougou, in March 2015. She was admitted for a voluminous bilateral painless cervical swelling, with no sign of local compression, having been operating for about a year. Biological tests showed signs of chronic inflammation;the imagery specified the benign character of these formations: adenomegalia. Confirmation of the diagnosis was made by pathological examination, describing the aspect of emperipolesis to histology and, immunohistochemistry, polytypic plasmacytosis and PS100 positive/CD1a histiocytosis negative. The treatment could not be properly carried out, in view of the early discharge, against medical advice from the patient. The evolution would have been marked, according to the parents, by a slight involution of swelling.

Rosai-Dorfman disease in the spleen of a pediatric patient:A case report

BACKGROUND Rosai–Dorfman disease(RDD)is a rare histiocytic proliferation of unknown etiology commonly found in children and adolescents.The common manifestation of RDD is massive and painless bilateral cervical lymphadenopathy with extranodal disease.While extranodal involvement in RDD is common,the spleen is an infrequent site of disease.CASE SUMMARY We report a 10-mo-old female infant with RDD presenting multiple splenic masses without cervical lymphadenopathy.She had fever,and blood tests showed leukocytosis,anemia,and elevated erythrocyte sedimentation rate and Creactive protein.Ultrasound,computed tomography,and magnetic resonance images demonstrated multiple splenic masses.Despite antibiotic therapy,her symptoms were not relived.She underwent diagnostic splenectomy and was discharged with recovery.CONCLUSION In pediatric patients with refractory infectious symptoms or hematological abnormalities,clinicians should suspect RDD,even in patients without significant lymphadenopathy.

Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier function.However, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could provide valuable insights into potential therapeutic strategies for Alzheimer's disease and related conditions.

Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases

Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.

Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials

Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Mitochondrial therapeutics and mitochondrial transfer for neurodegenerative diseases and aging

Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million deaths as a result of neurological diseases.

Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

TAU is a neuronal microtubule-associated protein preferentially located in axons.In a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying treatments.While for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,i.e.treatments that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development.Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function.Increasing amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers.These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases.Through a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

Microglial dysfunction and genetic risk for neurodegenerative disease

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases a re increasing in prevalence as world populations age.While tremendous progress has been made,our understanding of the mechanisms that underlie the development of these diseases remains far from com plete.More troubling,despite the growing emotional and financial toll being to ken by neurodegenerative disorders,existing treatment options are limited almost exclusively to those that help manage symptoms but that lack the ability to alter the progression of the disease(Liu et al.,2022).