scholarly journals Aids in Infants and Children

2019 ◽  
Vol 32 (11-12) ◽  
pp. 332-42
Author(s):  
Sunarto Sunarto
Keyword(s):  
Cell Damage ◽  
Neuronal Loss ◽  
Failure To Thrive ◽  
Heterosexual Transmission ◽  
Pediatric Aids ◽  
Lymphocytic Interstitial Pneumonia ◽  
And Function ◽  
Specific Symptoms ◽  
Worse Prognosis ◽  
Asymptomatic Hiv

 Children are infected by HIV, 80% vertically, from HIV infected mothetS mostly near or at delivery. Because heterosexual transmission of HIV among adults is more and more important it is estimated that at the end of this century there will be totally more than 10 million HIV infected children. Three quarters of HIV-infected babies show non specific symptoms at the early phase, including failure to thrive, chronic diarrhea, recurrent bacterial injections, mucocutanous infection. Cytotropism of HIV to neroe cells resul.ts tn inflammation, neroe cell damage and neuronal loss. Progressive neurologic abnormalities and developmental milestone regression or developmental retardation will be the results. Pneumocystics carinii infection has worse prognosis than lymphocytic interstitial pneumonia which more commonly occurred in HIV injected children. Diarrhea is a troublesome problem in children with AIDS. Kaposi's sarcoma and secondary cancer are rare in pediatric AIDS.  Anemia and thrombocytopenia is common among AIDS children. In developing countries children with AIDS die within the year following the appearance of the symptoms, whereas asymptomatic HIV-injected children will live longer with high risk of recurrent and opportunistic injections. The hallmark of AIDS in children is the same as in adults,iI.e. the decrease of the number and function of CD4 lymphocytes. This in turn influences the junctions of other immunocompetent cells and loss of immunity is the result. Many things are still unexplainable in children AIDS.

scholarly journals Sialic Acid—Modified Nanoparticles—New Approaches in the Glioma Management—Perspective Review

2021 ◽  
Vol 22 (14) ◽  
pp. 7494
Author(s):  
Przemyslaw Wielgat ◽  
Katarzyna Niemirowicz-Laskowska ◽  
Agnieszka Z. Wilczewska ◽  
Halina Car
Keyword(s):  
Sialic Acid ◽  
Clinical Observation ◽  
Malignant Cell ◽  
Cellular Heterogeneity ◽  
Molecular Processes ◽  
Management Perspective ◽  
Therapeutic Tools ◽  
And Function ◽  
Worse Prognosis

The cell surface is covered by a dense and complex network of glycans attached to the membrane proteins and lipids. In gliomas, the aberrant sialylation, as the final stage of glycosylation, is an important regulatory mechanism of malignant cell behavior and correlates with worse prognosis. Better understanding of the role of sialylation in cellular and molecular processes opens a new way in the development of therapeutic tools for human brain tumors. According to the recent clinical observation, the cellular heterogeneity, activity of brain cancer stem cells (BCSCs), immune evasion, and function of the blood–brain barrier (BBB) are attractive targets for new therapeutic strategies. In this review, we summarize the importance of sialic acid-modified nanoparticles in brain tumor progression.

scholarly journals Repair cell first, then regenerate the tissues and organs

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiao-Bing Fu
Keyword(s):  
Tissue Repair ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Severe Trauma ◽  
Basic Unit ◽  
Basic Process ◽  
Tissue Repair And Regeneration ◽  
Healing Tissue ◽  
Organ Repair ◽  
And Function

AbstractWound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly; however, the basic process of repair at the cell level is often neglected. Because the cell is the basic unit of organism structure and function; cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury. Then, damage to tissues and organs occurs with massive cell damage, apoptosis and even cell death. Thus, how to achieve the aim of perfect repair and regeneration? The basic process of tissue or organ repair and regeneration should involve repair of cells first, then tissues and organs. In this manuscript, it is my consideration about how to repair the cell first, then regenerate the tissues and organs.

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

scholarly journals Lysophosphatidic Acid Signaling in Diabetic Nephropathy

2019 ◽  
Vol 20 (11) ◽  
pp. 2850 ◽  
Author(s):  
Jong Lee ◽  
Donghee Kim ◽  
Yoon Oh ◽  
Hee-Sook Jun
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathways ◽  
Lysophosphatidic Acid ◽  
Kidney Diseases ◽  
Cell Damage ◽  
Cell Structure ◽  
Research Findings ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

Lysophosphatidic acid (LPA) is a bioactive phospholipid present in most tissues and body fluids. LPA acts through specific LPA receptors (LPAR1 to LPAR6) coupled with G protein. LPA binds to receptors and activates multiple cellular signaling pathways, subsequently exerting various biological functions, such as cell proliferation, migration, and apoptosis. LPA also induces cell damage through complex overlapping pathways, including the generation of reactive oxygen species, inflammatory cytokines, and fibrosis. Several reports indicate that the LPA–LPAR axis plays an important role in various diseases, including kidney disease, lung fibrosis, and cancer. Diabetic nephropathy (DN) is one of the most common diabetic complications and the main risk factor for chronic kidney diseases, which mostly progress to end-stage renal disease. There is also growing evidence indicating that the LPA–LPAR axis also plays an important role in inducing pathological alterations of cell structure and function in the kidneys. In this review, we will discuss key mediators or signaling pathways activated by LPA and summarize recent research findings associated with DN.

scholarly journals Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2–P2X7 pathway

2010 ◽  
Vol 207 (12) ◽  
pp. 2561-2568 ◽  
Author(s):  
Sandra Hubert ◽  
Björn Rissiek ◽  
Katjana Klages ◽  
Jochen Huehn ◽  
Tim Sparwasser ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Damage ◽  
Mouse Tumor ◽  
Single Domain Antibody ◽  
Cell Compartment ◽  
Selective Depletion ◽  
New Strategy ◽  
And Function ◽  
Deficient Mice

CD4+CD25+FoxP3+ regulatory T cells (T reg cells) play a major role in the control of immune responses but the factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD+) released during cell damage or inflammation results in ART2.2–mediated ADP-ribosylation of the cytolytic P2X7 receptor on T cells. We show that T reg cells express the ART2.2 enzyme and high levels of P2X7 and that T reg cells can be depleted by intravenous injection of NAD+. Moreover, lower T reg cell numbers are found in mice deficient for the NAD-hydrolase CD38 than in wild-type, P2X7-deficient, or ART2-deficient mice, indicating a role for extracellular NAD+ in T reg cell homeostasis. Even routine cell preparation leads to release of NAD+ in sufficient quantities to profoundly affect T reg cell viability, phenotype, and function. We demonstrate that T reg cells can be protected from the deleterious effects of NAD+ by an inhibitory ART2.2-specific single domain antibody. Furthermore, selective depletion of T reg cells by systemic administration of NAD+ can be used to promote an antitumor response in several mouse tumor models. Collectively, our data demonstrate that NAD+ influences survival, phenotype, and function of T reg cells and provide proof of principle that acting on the ART2–P2X7 pathway represents a new strategy to manipulate T reg cells in vivo.

scholarly journals Lesion-Induced Alterations in Astrocyte Glutamate Transporter Expression and Function in the Hippocampus

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Alexandra E. Schreiner ◽  
Eric Berlinger ◽  
Julia Langer ◽  
Karl W. Kafitz ◽  
Christine R. Rose
Keyword(s):  
Cell Damage ◽  
Glutamate Uptake ◽  
Hippocampal Slices ◽  
Glutamate Transporter ◽  
Reactive Astrocytes ◽  
Extracellular Glutamate ◽  
Sodium Imaging ◽  
Ca1 Area ◽  
And Function ◽  
Transporter Expression

Astrocytes express the sodium-dependent glutamate transporters GLAST and GLT-1, which are critical to maintain low extracellular glutamate concentrations. Here, we analyzed changes in their expression and function following a mechanical lesion in the CA1 area of organotypic hippocampal slices. 6-7 days after lesion, a glial scar had formed along the injury site, containing strongly activated astrocytes with increased GFAP and S100β immunoreactivity, enlarged somata, and reduced capability for uptake of SR101. Astrocytes in the scar’s periphery were swollen as well, but showed only moderate upregulation of GFAP and S100β and efficiently took up SR101. In the scar, clusters of GLT-1 and GLAST immunoreactivity colocalized with GFAP-positive fibers. Apart from these, GLT-1 immunoreactivity declined with increasing distance from the scar, whereas GLAST expression appeared largely uniform. Sodium imaging in reactive astrocytes indicated that glutamate uptake was strongly reduced in the scar but maintained in the periphery. Our results thus show that moderately reactive astrocytes in the lesion periphery maintain overall glutamate transporter expression and function. Strongly reactive astrocytes in the scar, however, display clusters of GLAST and GLT-1 immunoreactivity together with reduced glutamate transport activity. This reduction might contribute to increased extracellular glutamate concentrations and promote excitotoxic cell damage at the lesion site.

scholarly journals Application of Angio Optical Coherence Tomography and Flash Electroretinogram in the Study of Retinal Morphology and Function in High Myopia

2021 ◽  
Author(s):  
Mengdan Cao ◽  
Jinxiang Luo ◽  
Junyi Ouyang ◽  
Fen Nie ◽  
Xuanchu Duan
Keyword(s):  
Blood Flow ◽  
Optical Coherence Tomography ◽  
Dark Adaptation ◽  
High Myopia ◽  
Light Adaptation ◽  
Retinal Thickness ◽  
Cell Damage ◽  
Flow Density ◽  
Macular Area ◽  
And Function

Abstract Purpose: Using optical coherence tomography (OCTA) and flash electroretinography (F-ERG), we investigated changes to the retinal micromorphology and the overall function of the retina in eyes with different degrees of high myopia. Design: Case-control study. Participants: A total of 64 cases of 118 eyes with axial high myopia with diopters ranging from -−6.0 D to −15.0D were included in the study. The individuals were 18-40 years old.Methods: Subjects were divided into three groups according to the axial length (AL) of the eye and the spherical equivalent (SE)of the lens: the high myopia group (AL: ≤26 mm and SE: −6.0D to −9.0D) with 32 eyes, the ultra-high myopia group (AL: 26-28 mm and SE: -9.25D to -12.0D) with 43 eyes, and the extremely high myopia group (AL: ≥28 mm and SE: −12.25D to −15.0D) with 43 eyes. We used the OCTA measurements macular foveal retinal thickness (MRT), foveal avascular zone (FAZ), and superficial macular and deep retinal microvascular density, and the F-ERG measurements retinal dark-adaptation a-wave and b-wave, oscillation potential (OP) wave, light adaptation a-wave and b-wave, and 30-Hz flicker light amplitudes, which represent the functional state of the retina.Results: The differences in retinal thickness in the macular area between the three groups were only statistically significant within 1 mm of the fovea (P = 0.006). MRT was positively correlated with AL (r = 0.278, P = 0.002) and negatively correlated with SE (R = −0.200, P = 0.031). The difference in the FAZ area between the three groups was also statistically significant (P = 0.036), and FAZ was negatively correlated with AL (r = −0.377, p < 0.001) and positively correlated with SE (r = 0.192, P < 0.5). Both the superficial and deep blood flow density of the macular fovea were positively correlated with AL (p < 0.001). The superficial parafoveal blood flow density was negatively correlated with AL (r = −0.280, P = 0.002) but positively correlated with SE (R = 0.254, P = 0.006). The overall blood flow density of the deep retina, the parafoveal blood flow density, and the blood flow density around the fovea were negatively correlated with AL (p < 0.001) and positively correlated with myopic SE (p < 0.001). The dark-adaptation b-wave, maximum comprehensive response a-wave and b-wave, OP wave, bright-adaptation a-wave and b-wave, and 30-Hz flicker amplitudes of the retina were negatively correlated with AL and positively correlated with SE. The amplitudes of light adaptation a-wave and b-wave were[1] negatively correlated with the foveal avascular density (p < 0.001), and the average amplitude of the OP wave was positively correlated with the superficial retinal avascular density (p < 0.001).Conclusions: Before obvious pathological changes or central vision damage, the morphology and function of the macular area show subtle changes in patients with high myopia. As the degree of myopia increases and the axis of the eye increases, the activity of the cone cells in high myopia eyes decreases and the microvascular circulation in the inner retina and function of inner layer cells, such as non-proa cells, are affected. The changes of retinal dark adaptation are more sensitive than those of bright adaptation, which indicates that retinal rod cell damage may be earlier than cone cell damage in high myopia. Therefore, we believe that the combined use of OCTA and F-ERG can help in the early diagnosis and monitoring of patients at a high risk of myopia and to guide their clinical treatment.Because the p-value is clearly provided, the term “significantly” is not necessary (removed to reduce wordiness).

scholarly journals Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Fernando A. Vicentini ◽  
Catherine M. Keenan ◽  
Laurie E. Wallace ◽  
Crystal Woods ◽  
Jean-Baptiste Cavin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Neuronal Survival ◽  
Neuronal Loss ◽  
Structure And Function ◽  
Enteric Neurons ◽  
Intestinal Function ◽  
Gi Tract ◽  
Enteric Glia ◽  
And Function

Abstract Background The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and ENS. Microbiota-dependent molecular mechanisms of ENS neuronal survival and neurogenesis were also assessed. Results Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion secretion, and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia was only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion, but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, short-chain fatty acids (SCFA) were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo. Conclusions Our results demonstrate a role for the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies.

scholarly journals APOL1-G0protects podocytes in a mouse model of HIV-associated nephropathy

2019 ◽  
Author(s):  
Leslie A. Bruggeman ◽  
Zhenzhen Wu ◽  
Liping Luo ◽  
Sethu Madhavan ◽  
Paul E. Drawz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mouse Models ◽  
Kidney Diseases ◽  
Cell Damage ◽  
Loss Of Function ◽  
Protective Function ◽  
Chronic Kidney Diseases ◽  
Increased Risk ◽  
Podocyte Loss ◽  
And Function

ABSTRACTBackgroundAfrican polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival advantage against lethal trypanosomiasis but also an increased risk for several chronic kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed in renal cells, however, the pathogenic events that lead to renal cell damage and kidney disease are not fully understood.MethodsThe podocyte function ofAPOL1-G0versusAPOL1-G2in the setting of a known disease stressor was assessed using transgenic mouse models. Survival, renal pathology and function, and podocyte density were assessed in an intercross of a mouse model of HIVAN (Tg26) with two mouse models that express eitherAPOL1-G0orAPOL1-G2in podocytes.ResultsMice that expressed HIV genes developed heavy proteinuria and glomerulosclerosis, and had significant losses in podocyte numbers and reductions in podocyte densities. Mice that co-expressedAPOL1-G0and HIV had preserved podocyte numbers and densities, with fewer morphologic manifestations typical of HIVAN pathology. Podocyte losses and pathology in mice co-expressingAPOL1-G2and HIV were not significantly different from mice expressing only HIV. Podocyte hypertrophy, a known compensatory event to stress, was increased in the mice co-expressing HIV andAPOL1-G0, but absent in the mice co-expressing HIV andAPOL1-G2. Mortality and renal function tests were not significantly different between groups.ConclusionsAPOL1-G0expressed in podocytes may have a protective function against podocyte loss or injury when exposed to an environmental stressor. This function appears to be absent withAPOL1-G2expression, suggestingAPOL1-G2is a loss-of-function variant.

Sign in / Sign up

Export Citation Format

Share Document