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1.
Cell Mol Life Sci ; 81(1): 346, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134808

ABSTRACT

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS.


Subject(s)
Cuprizone , Demyelinating Diseases , Myelin Sheath , Oligodendroglia , Remyelination , Transcranial Magnetic Stimulation , Animals , Transcranial Magnetic Stimulation/methods , Oligodendroglia/metabolism , Demyelinating Diseases/therapy , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Mice , Myelin Sheath/metabolism , Disease Models, Animal , Mice, Transgenic , Motor Cortex/pathology , Motor Cortex/metabolism , Cell Survival , Mice, Inbred C57BL , Multiple Sclerosis/therapy , Multiple Sclerosis/pathology
2.
Materials (Basel) ; 17(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38998322

ABSTRACT

For the first time, this paper explores the role of hydration kinetics on microcrack development in cement mortars using the µ-CT technique with a resolution of 2.2 µm. Three binders were tested: fine-grained ordinary Portland cement (OPC) with Blaine fineness of 391 m2/kg, coarse-grained OPC made from the same clinker with Blaine fineness of 273 m2/kg, and H-cement as a representative of the alkali-activated binder. It was found that most microcracks have a width in the range of 5-10 µm, increasing their occurrence with the progress of sealed hydration. While H-cement and coarse-grained OPC showed a comparable number of microcracks, fine-grained OPC exhibited more than twice the number of microcracks. In this sense, high hydration kinetics induce more microcracks, promoting later coalescence into visible cracks and disintegration of concrete at the end. Therefore, durable concrete with minimum microcracks should be derived from slow hydration kinetics or alkali-activation processes.

3.
Neurosci Bull ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042298

ABSTRACT

Oligodendrocyte precursor cells (OPCs) are a heterogeneous multipotent population in the central nervous system (CNS) that appear during embryogenesis and persist as resident cells in the adult brain parenchyma. OPCs could generate oligodendrocytes to participate in myelination. Recent advances have renewed our knowledge of OPC biology by discovering novel markers of oligodendroglial cells, the myelin-independent roles of OPCs, and the regulatory mechanism of OPC development. In this review, we will explore the updated knowledge on OPC identity, their multifaceted roles in the CNS in health and diseases, as well as the regulatory mechanisms that are involved in their developmental stages, which hopefully would contribute to a further understanding of OPCs and attract attention in the field of OPC biology.

4.
Glia ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39077799

ABSTRACT

Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the brain; this process fails during demyelinating pathologies. Adenosine is emerging as an important player in oligodendrogliogenesis, by activating its metabotropic receptors (A1R, A2AR, A2BR, and A3R). We previously demonstrated that the Gs-coupled A2BR reduced differentiation of primary OPC cultures by inhibiting delayed rectifier (IK) as well as transient (IA) outward K+ currents. To deepen the unclear role of this receptor subtype in neuron-OL interplay and in myelination process, we tested the effects of different A2BR ligands in a dorsal root ganglion neuron (DRGN)/OPC cocultures, a corroborated in vitro myelination assay. The A2BR agonist, BAY60-6583, significantly reduced myelin basic protein levels but simultaneously increased myelination index in DRGN/OPC cocultures analyzed by confocal microscopy. The last effect was prevented by the selective A2BR antagonists, PSB-603 and MRS1706. To clarify this unexpected data, we wondered whether A2BRs could play a functional role on DRGNs. We first demonstrated, by immunocytochemistry, that primary DRGN monoculture expressed A2BRs. Their selective activation by BAY60-6583 enhanced DRGN excitability, as demonstrated by increased action potential firing, decreased rheobase and depolarized resting membrane potential and were prevented by PSB-603. Throughout this A2BR-dependent enhancement of neuronal activity, DRGNs could release factors to facilitate myelination processes. Finally, silencing A2BR in DRGNs alone prevents the increased myelination induced by BAY60-6583 in cocultures. In conclusion, our data suggest a different role of A2BR during oligodendrogliogenesis and myelination, depending on their activation on neurons or oligodendroglial cells.

5.
Chemosphere ; 363: 142949, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39067825

ABSTRACT

Gravimetry-based direct measurements of mass concentration require offline analysis which is not suited for field campaigns. Hence such campaigns rely on the estimation of mass concentration by indirect methods mostly calibrated in controlled laboratory conditions. Optical particle counter (OPC) employs algorithms converting the measured number concentration to mass concentration using appropriate conversion factors. The accuracy of such conversion has not been validated for widely varying atmospheric conditions. This study compares the mass concentration estimated by OPC with those directly obtained from gravimetry-based instruments for outdoor samples collected in Bathinda City, Punjab, India from January 2022 to November 2023. The difference in the gravimetrically measured and OPC predicted values quantified in terms of ratios (gravimetric to optically estimated mass concentration), came out to be 1.42 ± 0.77, 0.99 ± 0.51, and 1.17 ± 0.58 for PM10, PM2.5 and PM1, respectively. This difference when estimated with the back-up filter of OPC itself (C Factor), was 1.37 ± 0.66. More than half of the samples showed ratios outside the 0.8-1.2 range thus indicating under or over-estimation in the OPC predicted values. The probable role of variation in density, shape, and refractive index of atmospheric aerosol particles towards the observed inaccuracy of estimated mass concentration has been highlighted. In the absence of clear guidelines and protocols, the study suggests ways to improve the accuracy via periodic measurement of the C Factor and/or incorporating calibration factors in such measurements.

6.
Microbiol Spectr ; 12(7): e0002424, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38829114

ABSTRACT

The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity (n = 28/35) for HPV16 and HPV33 and a specificity of 97% (n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% (n = 17/20), while in samples with <750 µL plasma, it was 73% (n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.


Subject(s)
Cell-Free Nucleic Acids , DNA, Viral , Oropharyngeal Neoplasms , Papillomavirus Infections , Polymerase Chain Reaction , Humans , DNA, Viral/blood , DNA, Viral/genetics , Papillomavirus Infections/diagnosis , Papillomavirus Infections/blood , Papillomavirus Infections/virology , Cell-Free Nucleic Acids/blood , Polymerase Chain Reaction/methods , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/diagnosis , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Female , Sensitivity and Specificity , Male , Middle Aged , Aged , Human papillomavirus 16/genetics , Human papillomavirus 16/isolation & purification , Human Papillomavirus Viruses
7.
Viruses ; 16(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38932197

ABSTRACT

HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.


Subject(s)
Head and Neck Neoplasms , Human papillomavirus 16 , Papillomavirus Infections , Phylogeny , Humans , Papillomavirus Infections/virology , Papillomavirus Infections/epidemiology , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/epidemiology , Human papillomavirus 16/genetics , Human papillomavirus 16/classification , Female , Genetic Variation , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , Genome, Viral , Anus Neoplasms/virology , Anus Neoplasms/epidemiology , Male , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/genetics
8.
Article in English | MEDLINE | ID: mdl-38909567

ABSTRACT

OPC-61815 is an intravenous formulation vasopressin antagonist designed to treat heart failure patients, especially who have difficulty in oral intake. Tolvaptan together with DM-4103 and DM-4107 are considered as the major metabolites of OPC-61815 biotransformed in the liver via cytochrome P450 (CYP) 3A. An efficient and robust ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of OPC-61815 and its three metabolites in human plasma was developed and fully validated. To our best knowledge, it was the first published method that simultaneously quantified all of these four analytes in only one run. Simple and rapid sample preparation procedure and very short UPLC-MS/MS run time (3.5 min) offered OPC-61815 and its metabolites relatively high throughput detection, which was greatly beneficial to further clinical bio-sample analysis. The method showed good linearity and sufficient sensitivity in the range of 2.00-1000 ng/mL with a low limit of quantitation (2.00 ng/mL) for each analyte. For samples with concentrations above 1000 ng/mL, 100-fold dilution with blank plasma before sample preparation was accepted. High precision and accuracy, high selectivity and satisfactory recovery of this method were demonstrated. For all of the four analytes, no significant matrix effect or carry-over was observed. The stability of analytes and internal standards under different conditions were evaluated to ensure they were stable during the whole period of storage, preparation and detection. Also, re-injection reproducibility was investigated. In addition, the conversion test showed that almost no OPC-61815 converted into DM-4103 and DM-4107 during sample processing, while attention should be paid to the concentration difference between OPC-61815 and tolvaptan in bioanalysis. The developed UPLC-MS/MS method was successfully applied to an open, single and multiple dose administration phase I trial for monitoring the pharmacokinetics of OPC-61815. This work provided a promising way for further pharmacokinetic study of OPC-61815.


Subject(s)
Tandem Mass Spectrometry , Tolvaptan , Tandem Mass Spectrometry/methods , Humans , Chromatography, High Pressure Liquid/methods , Reproducibility of Results , Tolvaptan/blood , Tolvaptan/chemistry , Linear Models , Limit of Detection , Benzazepines/blood , Benzazepines/pharmacokinetics , Benzazepines/chemistry , Liquid Chromatography-Mass Spectrometry
10.
Front Cell Neurosci ; 18: 1369730, 2024.
Article in English | MEDLINE | ID: mdl-38694535

ABSTRACT

Demyelination is typically followed by a remyelination process through mature oligodendrocytes (OLs) differentiated from precursor cells (OPCs) recruited into the lesioned areas, however, this event usually results in uncompleted myelination. Potentiation of the remyelination process is an important target for designing effective therapeutic strategies against white matter loss. Here, it was evaluated the remyelinating effect of different ß-carbolines that present differential allosteric modulation on the GABAA receptor expressed in OLs. For this, we used a focalized demyelination model in the inferior cerebellar peduncle (i.c.p.) of rats (DRICP model), in which, demyelination by ethidium bromide (0.05%) stereotaxic injection was confirmed histologically by staining with Black-Gold II (BGII) and toluidine blue. In addition, a longitudinal analysis with diffusion-weighted magnetic resonance imaging (dMRI) was made by computing fractional anisotropy (FA), apparent diffusion coefficient (ADC) and diffusivity parameters to infer i.c.p. microstructural changes. First, dMRI analysis revealed FA decreases together with ADC and radial diffusivity (RD) increases after demyelination, which correlates with histological BGII observations. Then, we evaluated the effect produced by three allosteric GABAA receptor modulators, the N-butyl-ß-carboline-3-carboxylate (ß-CCB), ethyl 9H-pyrido [3,4-b]indole-3-carboxylate (ß-CCE), and 4-ethyl-6,7-dimethoxy-9H-pyrido [3,4-b]indole-3-carboxylic acid methyl ester (DMCM). The results indicated that daily systemic ß-CCB (1 mg/Kg) or ß-CCE (1 mg/Kg) administration for 2 weeks, but not DMCM (0.35 mg/Kg), in lesioned animals increased FA and decreased ADC or RD, suggesting myelination improvement. This was supported by BGII staining analysis that showed a recovery of myelin content. Also, it was quantified by immunohistochemistry both NG2+ and CC1+ cellular population in the different experimental sceneries. Data indicated that either ß-CCB or ß-CCE, but not DMCM, produced an increase in the population of CC1+ cells in the lesioned area. Finally, it was also calculated the g-ratio of myelinated axons and observed a similar value in those lesioned animals treated with ß-CCB or ß-CCE compared to controls. Thus, using the DRICP model, it was observed that either ß-CCB or ß-CCE, positive modulators of the GABAA receptor in OLs, had a potent promyelinating effect.

11.
Heliyon ; 10(9): e29771, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38737286

ABSTRACT

As health and safety issues emanating from human activities on terrestrial environment is becoming ever challenging, the production of Ordinary Portland Cement is identified as a key contributor. This technology threatens environmental quality by emitting significant quantity of carbon dioxide (CO2) that threatens Net Zero delivery. Consequently, the development of cement alternatives with substantial CO2 reduction/sequestration during production has become imperative. Geopolymers obtained from industrial residues are poised as promising alternatives in managing environmental systems but selection of appropriate method of activation has limited their wider industrial applications. This article discusses four key activation methods and their combinations used in four main feedstocks to advise on their energy requirements, product compressive strength and environmental/industrial applications. Reviewing and characterising 302 published literatures with focus on most relevant and recent advances in the field, this review found that hybrid techniques combining mechanical activation method produces geopolymers with the highest compressive strength and thus the best method. Geopolymer made by mechano-chemical activation method of slag achieved the highest compressive strength while geopolymer produced by microwave assisted activation of clay and ultrasonic activation of fly ash cum slag are most economical in curing energy demand. Hybrid activation is the current development in the field and integration of this method with mechanical activation is poised as the future geopolymer activation technology as it demonstrates greatest efficiency potential.

12.
Ther Adv Infect Dis ; 11: 20499361241255261, 2024.
Article in English | MEDLINE | ID: mdl-38812710

ABSTRACT

Background: Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to empirical treatment and emergence of antifungal resistance (AFR). This study sought to investigate the prevalence of oropharyngeal candidiasis and assess the antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with human immunodeficiency virus. Additionally, we evaluated the correlation between oropharyngeal candidiasis and CD4 T cell as well as viral load counts. Methods: A descriptive cross-sectional study was carried out from April to October 2023 in which 384 people living with HIV underwent clinical examination for oral lesions. Oropharyngeal swabs were collected and cultured on Sabouraud Dextrose agar to isolate Candida species which were identified using the matrix assisted laser desorption ionization time of flight mass spectrometry. Additionally, the antifungal susceptibility profile of Candida isolates to six antifungal drugs was determined using VITEK® (Marcy-l'Étoile, France) compact system. Data on viral load were retrieved from records, and CD4 T cell count test was performed using Becton Dickinson Biosciences fluorescent antibody cell sorter presto. Results: The prevalence of oropharyngeal candidiasis was 7.6%. Oropharyngeal candidiasis was significantly associated with low CD4 T cell count and high viral load. A total of 35 isolates were obtained out of which Candida albicans comprised of 20 (57.1%) while C. tropicalis and C. glabrata comprised 4 (11.4%) each. C. parapsilosis, C. dubliniensis and C. krusei accounted for 2 (5.7%) each. Additionally, 7 (20%) isolates were resistant to fluconazole, 1 (2.9%) to flucytocine and 0.2 (5.7%) isolates were intermediate to caspofungin. However, specific specie isolates like C. albicans showed 20% (4/20), C. glabrata 50% (2/4) and C. krusei 50% (1/2) resistance to fluconazole. Additionally, C. krusei showed 50% resistance to flucytosine. Conclusion: The prevalence of oropharyngeal candidiasis (OPC) among people living with HIV was low, and there was a significant association between OPC and CD4 T cell count as well as viral load. C. albicans was the most frequently isolated oropharyngeal Candida species. C. glabrata and C. krusei exhibited the highest AFR among the non-albicans Candida species. The highest resistance was demonstrated to fluconazole.

13.
Sci Total Environ ; 941: 173450, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38797422

ABSTRACT

Conventional techniques for monitoring pollen currently have significant limitations in terms of labour, cost and the spatiotemporal resolution that can be achieved. Pollen monitoring networks across the world are generally sparse and are not able to fully represent the detailed characteristics of airborne pollen. There are few studies that observe concentrations on a local scale, and even fewer that do so in ecologically rich rural areas and close to emitting sources. Better understanding of these would be relevant to occupational risk assessments for public health, as well as ecology, biodiversity, and climate. We present a study using low-cost optical particle counters (OPCs) and the application of machine learning models to monitor particulate matter and pollen within a mature oak forest in the UK. We characterise the observed oak pollen concentrations, first during an OPC colocation period (6 days) for calibration purposes, then for a period (36 days) when the OPCs were distributed on an observational tower at different heights through the canopy. We assess the efficacy and usefulness of this method and discuss directions for future development, including the requirements for training data. The results show promise, with the derived pollen concentrations following the expected diurnal trends and interactions with meteorological variables. Quercus pollen concentrations appeared greatest when measured at the canopy height of the forest (20-30 m). Quercus pollen concentrations were lowest at the greatest measurement height that is above the canopy (40 m), which is congruent with previous studies of background pollen in urban environments. The attenuation of pollen concentrations as sources are depleted is also observed across the season and at different heights, with some evidence that the pollen concentrations persist later at the lowest level beneath the canopy (10 m) where catkins mature latest in the season compared to higher catkins.


Subject(s)
Air Pollutants , Environmental Monitoring , Machine Learning , Particulate Matter , Pollen , Quercus , Environmental Monitoring/methods , Particulate Matter/analysis , Air Pollutants/analysis , United Kingdom , Air Pollution/statistics & numerical data , Spatio-Temporal Analysis
14.
Br J Pharmacol ; 181(17): 3263-3281, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38742374

ABSTRACT

BACKGROUND AND PURPOSE: ApTOLL is an aptamer selected to antagonize toll-like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. EXPERIMENTAL APPROACH: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic-activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). KEY RESULTS: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. CONCLUSION AND IMPLICATIONS: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.


Subject(s)
Aptamers, Nucleotide , Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred C57BL , Multiple Sclerosis , Animals , Humans , Multiple Sclerosis/drug therapy , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Encephalomyelitis, Autoimmune, Experimental/immunology , Mice , Aptamers, Nucleotide/pharmacology , Female , Cuprizone , Oligodendroglia/drug effects , Cells, Cultured , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/antagonists & inhibitors , Myelin Sheath/drug effects , Myelin Sheath/metabolism
15.
Neurotherapeutics ; 21(4): e00379, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38797642

ABSTRACT

Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-ß), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In line with previous reports, we demonstrate that IFN-ß and DMF inhibit OPC proliferation, while CDB had no effect. None of the drugs exhibited cytotoxic effects at the physiological concentrations tested in vitro. In a differentiation assay, none of the drugs were able to promote differentiation, under inflammatory or basal conditions. To study drug effects on iOPCs, we monitored MHC expression in vitro with live cell imaging using cells isolated from MHC reporter mice. IFN-ß suppressed induction of MHC class II, and DMF led to suppression of both class I and II. CDB had no effect on MHC induction. We conclude that promoting proliferation and differentiation and suppressing iOPC induction under inflammatory conditions may require separate therapeutic strategies and must be balanced for maximal repair. Our in vitro MHC screening assay can be leveraged across cell types to test the effects of drug candidates and disease-related stimuli.

16.
Methods Mol Biol ; 2782: 167-173, 2024.
Article in English | MEDLINE | ID: mdl-38622401

ABSTRACT

Microglia and oligodendrocyte precursor cells (OPCs) are critical glia subsets in the central nervous system (CNS) and are actively engaged in a body of diseases, such as stroke, Alzheimer's disease, multiple sclerosis, etc. Microglia and OPC serve as compelling tools for the study of CNS diseases as well as the repair and damage of myelin sheath in vitro. In this protocol, we summarized a method which is capable of using the same batch of new-born mice to isolate and culture microglia and OPCs. It integrates the characteristics of practicality, convenience, and efficiency, providing a convenient, easy, and reliable technique for research.


Subject(s)
Microglia , Oligodendrocyte Precursor Cells , Mice , Animals , Cell Differentiation/physiology , Myelin Sheath , Central Nervous System , Oligodendroglia
17.
Materials (Basel) ; 17(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38673118

ABSTRACT

This study presents a comprehensive investigation into the mechanical properties of Basic Magnesium Sulfate Cement Concrete (BMSC) in comparison to Ordinary Portland Cement Concrete (OPC) within reinforced concrete components. The main objective is to evaluate BMSC's applicability for practical engineering purposes, with a focus on its with early high strength, improved toughness, and superior crack resistance compared to conventional concrete. Experimental procedures involved fabricating beam specimens using OPC concrete with a C40 strength grade, alongside BMSC beams with varying strength grades (C30, C40, and C50). These specimens underwent bending resistance tests to analyze crack patterns and mechanical characteristics. The findings reveal that BMSC beams demonstrate enhanced bending and tensile properties at equivalent strength grades compared to OPC beams. Particularly, cracking mainly occurred at the mid-span region of BMSC beams, characterized by narrower cracks, indicating superior crack resistance. However, it was noted that the toughness of BMSC beams decreases as the strength grade increases. The maximum mid-span deflection of the BMSC test beam was smaller than that of the OPC test beam, which was 3.8 mm and 2.6 mm, respectively. The maximum crack width of the OPC beam was 4.7 times that of the BMSC beam. To facilitate practical implementation, the study developed calculation models for estimating the crack bending distance and ultimate bending distance in BMSC beams, offering valuable tools for engineering design and optimization. Overall, this research provides significant insights into the mechanical behavior of BMSC, presenting potential advantages for structural engineering applications.

18.
Sensors (Basel) ; 24(7)2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38610283

ABSTRACT

This article presents the hardware and software architectures used to implement the Modbus Extension (ModbusE) IIoT gateway, the performance of the acquisition cycle at the PRU real-time programmable core level, the acquisition cycle communication flow-dispatcher-OPC UA server (Linux)-OPC UA client (Windows) as well as the performance analysis of data communications between the IIoT ModbusE gateway and the OPC UA client (Windows). In order to be able to implement both the ModbusE acquisition cycle and the OPC UA server, the BeagleBone Black Board was chosen as the hardware platform. This board uses the Sitara AM335x processor (Texas Instruments (TI), Dallas, TX, USA) from Texas Instruments. Thus, the acquisition cycle was implemented on the PRU0 real-time core, and the OPC UA server, running under the Linux operating system, was implemented on the ARM Cortex A8 processor. From the analysis of the communication speed of the messages between the OPC UA client and the ModbusE servers, it was found that the ModbusE acquisition cycle speed was higher than the acquisition speed of the OPC UA client.

19.
Sensors (Basel) ; 24(8)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38676117

ABSTRACT

Aerosols, as well as suspended particulate matter, impact atmospheric pollution, the climate, and human health, directly or indirectly. Particle size, chemical composition, and other aerosol characteristics are determinant factors for atmospheric pollution dynamics and more. In the last decade, low-cost devices have been widely used in instrumentation to measure aerosols. However, they present some issues, such as the problem of discriminating whether the aerosol is composed of liquid particles or solid. This issue could lead to errors in the estimation of mass concentration in monitoring environments where there is fog. In this study, we investigate the use of an optical particle counter (OPC) coupled to a quartz crystal microbalance with an integrated microheater (H-QCM) to enhance measurement performances. The H-QCM was used not only to measure the collected mass on its surface but also, by using the integrated microheater, it was able to heat the collected mass by performing heating cycles. In particular, we tested the developed system with aerosolized saline solutions of sodium chloride (NaCl), with three decreasing concentrations of salt and three electronic cigarette solutions (e-liquid), with different concentrations of propylene glycol and glycerin mixtures. The results showed that the OPC coherently counted the salt dilution effects, and the H-QCM output confirmed the presence of liquid and solid particles in the aerosols. In the case of e-liquid aerosols, the OPC counted the particles, and the HQCM output highlighted that in the aerosol, there were no solid particles but a liquid phase only. These findings contribute to the refinement of aerosol measurement methodologies by low-cost sensors, fostering a more comprehensive understanding.

20.
Neuron ; 112(13): 2177-2196.e6, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38653248

ABSTRACT

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.


Subject(s)
Myelin Sheath , Neovascularization, Physiologic , Pericytes , Animals , Pericytes/metabolism , Pericytes/drug effects , Mice , Myelin Sheath/metabolism , Neovascularization, Physiologic/drug effects , Neovascularization, Physiologic/physiology , Growth Hormone/metabolism , Growth Hormone/pharmacology , Animals, Newborn , Hypoxia/metabolism , Cell Differentiation/drug effects , Mice, Inbred C57BL , Oligodendrocyte Precursor Cells/metabolism , Oligodendrocyte Precursor Cells/drug effects , Receptors, Somatotropin/metabolism , Receptors, Somatotropin/genetics , Angiogenesis
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