The Influence of Concrete Sludge from Residual Concrete on Fresh and Hardened Cement Paste Properties.

In the concrete manufacturing industry, a large amount of waste is generated. Such waste can be utilised in the production of more sustainable products with a low carbon footprint. In this study, concrete sludge, a difficult-to-utilise waste that is obtained from residual concrete by washing a concrete truck, was investigated. During washing, aggregates from the concrete mixture are separated, and the remaining insoluble fine particles combine with water to form concrete sludge. Dried and wet concrete sludge were used in the tests. Samples with different compositions were produced with dried and wet concrete sludge, cement, superplasticiser, and tap water. Seven cement pastes with different compositions were made by partially replacing cement with dried concrete sludge (0%, 5%, 10%, 15%, 20%, 25%, and 30%). In compositions with wet concrete sludge, cement was replaced by the same amounts as in the case of dried concrete sludge. The slump, setting time, and their changes with different amounts of concrete sludge were determined for fresh cement pastes. It was found that with different forms of concrete sludge, the technological properties of the mixtures change, and the setting time decreases. The density and compressive and flexural strength results were confirmed by SEM and XRD tests. The research results show that dry concrete sludge causes the deterioration of the mechanical properties of cement stone, while wet concrete sludge improves the mechanical properties of cement stone. However, it was found that replacing 5% cement with dry concrete sludge does not significantly affect the properties of hardened cement stone. In mixes with wet concrete sludge, the recommended amount of replaced cement is 10%, because the technological properties of the mixture are strongly influenced by larger amounts.

TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small-molecule therapeutic agents.

TREM2 is thyroid hormone regulated making the TREM2 pathway druggable with ligands for thyroid hormone receptor.

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. We report here that TREM2 is a thyroid hormone regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone. Both endogenous thyroid hormone and sobetirome, a synthetic thyroid hormone agonist drug, suppress pro-inflammatory cytokine production from myeloid cells including macrophages that have been treated with the SARS-CoV-2 spike protein which produces a strong, pro-inflammatory phenotype. Thyroid hormone agonism was also found to induce phagocytic behavior in microglia, a phenotype consistent with activation of the TREM2 pathway. The thyroid hormone antagonist NH-3 blocks the anti-inflammatory effects of thyroid hormone agonists and suppresses microglia phagocytosis. Finally, in a murine experimental autoimmune encephalomyelitis (EAE) multiple sclerosis model, treatment with Sob-AM2, a CNS-penetrating sobetirome prodrug, results in increased Trem2 expression in disease lesion resident myeloid cells which correlates with therapeutic benefit in the EAE clinical score and reduced damage to myelin. Our findings represent the first report of endocrine regulation of TREM2 and provide a unique opportunity to drug the TREM2 signaling pathway with orally active small molecule therapeutic agents.

A microwave method for plastic embedding of nervous tissue for light and electron microscopy.

BACKGROUND: Fast, effective, and rapid processing of central nervous system (CNS) tissue with good preservation of myelin, especially in tissue from diseased mice, is important to many laboratories studying neurosciences. NEW METHOD: In this paper, we describe a new method to process and embed CNS tissue from mice. Spinal cords and optic nerves from naive C57BL/6 mice were used to standardize the microwave protocol following perfusion with fixative. The CNS tissue was processed and embedded using the microwave embedding protocol. RESULTS: We observed that the tissue is well preserved and good quality light and electron microscope images were obtained after using the microwave embedding protocol. COMPARISON WITH EXISTING METHODS: Traditional way of embedding CNS tissue in resin is challenging and time consuming. The microwave technology offers an efficient way to quickly embed CNS tissue while preserving morphology and retaining the integrity of the myelin. CONCLUSIONS: This new method is fast, reliable and an effective way to embed CNS tissue in resin.

Effects of lipoic acid on primary murine microglial cells.

The anti-oxidant lipoic acid (LA) is beneficial in murine models of multiple sclerosis (MS) and has recently been shown to slow brain atrophy in secondary progressive MS. The mechanism of these effects by LA is incompletely understood but may involve effects on microglia. The objective of this study is to understand how LA affects microglial cells. We cultured primary microglial cells from C57BL/6 adult mice brains and stimulated the cells with lipopolysaccharide (LPS) and interferon gamma (IFN-γ) in the presence or absence of LA. We demonstrate the inhibition of phagocytosis, rearrangement of actin, and formation of membrane blebs in stimulated microglia in the presence of LA. These experiments suggest that LA causes changes in microglial actin, which may lead to alterations in phagocytosis, mobility, and migration.

Myelin repair stimulated by CNS-selective thyroid hormone action.

Oligodendrocyte processes wrap axons to form neuroprotective myelin sheaths, and damage to myelin in disorders, such as multiple sclerosis (MS), leads to neurodegeneration and disability. There are currently no approved treatments for MS that stimulate myelin repair. During development, thyroid hormone (TH) promotes myelination through enhancing oligodendrocyte differentiation; however, TH itself is unsuitable as a remyelination therapy due to adverse systemic effects. This problem is overcome with selective TH agonists, sobetirome and a CNS-selective prodrug of sobetirome called Sob-AM2. We show here that TH and sobetirome stimulated remyelination in standard gliotoxin models of demyelination. We then utilized a genetic mouse model of demyelination and remyelination, in which we employed motor function tests, histology, and MRI to demonstrate that chronic treatment with sobetirome or Sob-AM2 leads to significant improvement in both clinical signs and remyelination. In contrast, chronic treatment with TH in this model inhibited the endogenous myelin repair and exacerbated disease. These results support the clinical investigation of selective CNS-penetrating TH agonists, but not TH, for myelin repair.

Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model.

Cortical lesions are a crucial part of MS pathology and it is critical to determine that new MS therapies have the ability to alter cortical inflammatory lesions given the differences between white and gray matter lesions. We tested lipoic acid (LA) in a mouse focal cortical EAE model. Brain sections were stained with antibodies against CD4, CD11b and galectin-3. Compared with vehicle, treatment with LA significantly decreased CD4+ and galectin-3+ immune cells in the brain. LA treated mice had fewer galectin-3+ cells with no projections indicating decrease in the number of infiltrating monocytes. LA significantly reduces inflammation in a focal cortical model of MS.

The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids.

Co-administration of opioids and cannabinoids can enhance pain relief even when administered on different days. Repeated systemic administration of morphine has been shown to enhance the antinociceptive effect of tetrahydrocannabinol (THC) administered 12h later, and repeated microinjection of the cannabinoid receptor agonist HU-210 into the ventrolateral periaqueductal gray (PAG) has been shown to enhance the antinociceptive effect of morphine administered 1 day later. The primary objective of the present study was to test the hypothesis that this cannabinoid/opioid interaction is bidirectional. Experiment 1 showed that microinjection of morphine into the ventrolateral PAG of male Sprague-Dawley rats twice daily for 2 days enhanced the antinociceptive effect of HU-210 measured 1 day later. In Experiment 2, twice daily systemic injections of THC enhanced the antinociceptive effect of morphine administered 1 day later. These results complement the previously mentioned studies by showing that morphine and cannabinoid interactions are bidirectional and that the ventrolateral PAG plays an important role in this effect. In contrast to the PAG, repeated administration of HU-210 or the cannabinoid receptor agonist, WIN 55,212-2, into the RVM had a neurotoxic effect. Rats became ill following repeated cannabinoid administration whether given alone or with morphine. Presumably, this neurotoxic effect was caused by the high cannabinoid concentration following RVM microinjection because rats did not become ill following repeated systemic THC administration. These findings indicate that alternating opioid and cannabinoid treatment could produce a longer lasting and more potent analgesia than either compound given alone.