Search Results (216)

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

The physical and rheological properties of mucilage hydrogels derived from the cladodes of Opuntia ficus-indica (L. Mill) were compared with those of commercial pectin for potential applications in the food industry. All hydrogels—formulated by incorporating sucrose and either calcium chloride or calcium carbonate to promote favorable gel network formation—exhibited pseudoplastic (shear-thinning) behavior. The flow characteristics of the hydrogels prepared with mucilage or pectin conformed to the Casson fluid model. Moreover, all samples consistently displayed loss modulus (G″) values exceeding their corresponding storage modulus (G′) values, indicating a dominant viscous behavior over elastic properties. The ζ-potential of all samples was negative across the pH range studied. Mucilage-based samples exhibited lower ionizability per unit mass and reduced phase stability compared to those containing pectin. Principal component analysis (PCA) revealed that mucilage hydrogels exhibited multivariate profiles similar to pectin hydrogels containing calcium carbonate, though the latter demonstrated greater polydispersity than standard pectic gels. Infrared spectroscopy further highlighted distinct spectral differences between pectins and mucilages, offering valuable insights into their respective functional characteristics. Collectively, these findings underscore the potential of Opuntia ficus-indica mucilages as viable additives in food formulations. Full article

Hypocalcemia is common in dairy cows within the first 72 h post-calving, and can be either clinical or subclinical. Early detection is critical, but traditional laboratory tests are time-consuming and cow-side tests remain costly. A classic symptom of hypocalcemia is reduced ear skin temperature, which has been explored as a diagnostic tool in a previous study, but was not recommended at the end. Additionally, ambient temperature was found to strongly influence ear skin temperature, complicating diagnosis. The present study investigates infrared thermography of the ear as a potential non-invasive method for helping in the detection of hypocalcemia in Holstein cows. In order to differ from the previous study, with the goal of improving diagnosis accuracy, this research analyzed the entire ear temperature using infrared imaging software. Ambient temperature was factored in by categorizing samples into two groups based on air temperature: colder (−1.6 to 14.6 °C) and hotter (15.3 to 31.2 °C). Forty-two cows were monitored during the perinatal period, with blood samples and thermographic images taken twice a day until 48 h after calving. This study found that the median surface temperature of the ear correlated strongly with environmental temperature (r = 0.806, p < 0.001) and weakly with blood ionized calcium levels (r = 0.310, p < 0.01). In colder air temperatures, ear surface temperature was significantly different between healthy and hypocalcemic cows (p = 0.014). Logistic regression models were used to assess ionized calcium status based on different combinations of ear surface temperature, its difference from air temperature, and days in milk. In hotter air temperatures, only ear surface temperature, with no other covariates, was able to generate a valid model (p = 0.029). In colder air temperatures, multiple combinations of those variables generated valid models (p < 0.05), with the difference between ear and air temperature, together with days in milk, performing the best. Thus, this study concluded that ear surface temperature obtained through infrared thermography, while not promising for warmer environments, does show application potential for helping in the detection of hypocalcemia in colder environments. Full article

Increasing water scarcity in arid regions has prompted the mining industry to develop strategies to maximize water recovery and reuse, especially in tailings treatment processes. In this context, the present investigation evaluated the effects of sodium polyacrylate (NaPA) on the compressibility and viscoelasticity of clayey tailings in the presence of hard water containing calcium and magnesium. To this end, clayey slurries were analyzed using rheological tests (rheograms and oscillatory viscoelasticity), zeta potential measurements, and compressibility tests using batch centrifugation. The yield stress was determined using the Herschel–Bulkley model, while the compressive yield stress (Py(Φ)) was calculated as a key indicator to characterize the degree of sediment consolidation. The results showed that NaPA, due to its anionic nature and high degree of ionization at pH 8, induces effective particle dispersion by increasing electrostatic repulsion and decreasing the interaction force between particles, which reduces both rheological parameters and compressive yield stress. For the 70/30 quartz/kaolin mixture, the yield stress decreased from 70.54 to 61.64 Pa in CaCl₂ and from 57.51 to 52.95 Pa in MgCl₂ in the presence of NaPA. It was also observed that suspensions in the presence of magnesium ions presented greater compressibility than those with calcium, attributable to the greater hydration radius of magnesium (10.8 Å), which favors less dense and more easily deformable network structures. Furthermore, a higher proportion of kaolin in the mixture resulted in higher yield stresses, a product of the clay’s laminar structure, colloidal size, and high surface area, both in the absence and presence of NaPA. Overall, the results show that incorporating NaPA significantly improves the compressibility and rheology of clayey tailings in hard water, offering a promising alternative for optimizing water recovery and improving tailings management efficiency in the context of water restrictions. Full article

Background: Elevated levels of methylmalonic acid (MMA) are observed in the bodily fluids and tissues of patients with methylmalonic aciduria, a metabolic disorder characterized by manifestations such as vomiting, lethargy, muscle weakness, seizures, and coma. Objectives and Methods: To better understand the neuropathological mechanisms underlying this condition, we investigated the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of MMA on antioxidant defenses, citric acid cycle functioning, and glial reactivity in the cerebral cortex and striatum of Wistar rats. Amino acid levels were also quantified. Results: i.p. and i.c.v. administration of MMA decreased reduced glutathione levels and altered the activities of different antioxidant enzymes in the cortex and striatum. The activity of the citric acid cycle enzyme succinate dehydrogenase was diminished in both brain regions by i.p. and i.c.v. administration. Citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities were further inhibited in the striatum. Furthermore, the i.p. administration increased glial fibrillary acidic protein (GFAP) and glucose transporter 1 (GLUT1) levels, whereas i.c.v. administration elevated GFAP and ionized calcium-binding adaptor molecule 1 (IBA1) levels in the striatum, suggesting glial activation. In contrast, no significant changes in glial markers were detected in the cortex. Moreover, synaptophysin levels remained unaltered in both regions. Finally, i.p. administration increased glutamate, glycine, and serine levels and reduced tyrosine concentrations in the striatum. Conclusions: Our findings indicate that oxidative stress, bioenergetic dysfunction, and glial reactivity induced by MMA may contribute to the neurological deficits observed in methylmalonic aciduria. Full article

Cognitive problems are associated with impaired learning ability and memory dysfunction. Neuroinflammation has been identified as an important factor in the progression of anxiety and depressive disorders. Zingerone is a phenolic alkanone derived from ginger (Zingiber officinale Roscoe), which is known for its antioxidant and anti-inflammatory properties. A number of studies have investigated the effect of zingerone on neuroinflammation and cognitive impairment. However, this evidence has not been systematically reviewed. This study sought to systematically review the effect of zingerone on neuroinflammation and neurobehavioural changes associated with memory and learning impairment and anxiety-like and depressive-like behaviours. A systematic review was conducted using pre-defined search criteria on Google Scholar, Scopus and Web of Science. The records obtained were screened based on inclusion criteria, and data was extracted from the included studies. Out of the 482 studies that were identified, only 9 studies met the inclusion criteria. Neuroinflammatory markers such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α) and ionized calcium binding adaptor molecule (IBA-1), as well as behavioural parameters including Morris water maze, Y-Maze, recognition test, passive avoidance test, elevated plus maze, sucrose preference test and forced swimming test were measured. Zingerone exhibited anti-neuroinflammatory effects by improving IL-1β, IL-6 and TNF-α levels. However, zingerone did not show any significant changes on activated microglia. The anti-neuroinflammatory mechanisms of zingerone were linked to the inhibition of nuclear factor kappa B (NF-kB) activation and the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, as well as the reduction in neuronal nitric oxide synthase (nNOS). The anxiolytic and anti-depressive effects of zingerone were also associated with an improvement in cortical cholinergic transmission, the mitigation of oxidative stress and the upregulation of neurotransmitters such as serotonin and dopamine. This review provides scientific evidence on the cognitive enhancing and neuroprotective mechanisms of zingerone, which may be beneficial for future experimental investigations. Full article

Background: Postoperative hypoparathyroidism is a common complication of thyroid surgery. Sunlight is a natural source of ultraviolet B (UVB) radiation, which facilitates the synthesis of vitamin D3 in the skin. Inadequate sunlight exposure has been linked to vitamin D deficiency, potentially exacerbating the risk of hypocalcemia in patients undergoing thyroid surgery. The aim of the present study is to evaluate the effect of sunshine levels on postoperative hypoparathyroidism. Method: We retrospectively evaluated patients that underwent total thyroidectomies at two different centers (Thessaloniki and Rhodes) by the same surgical team from 2021 to 2023 in terms of postoperative hypoparathyroidism. We compared the sunshine levels at each center the year before surgery and correlated them with postoperative levels of parathyroid hormone, serum ionized calcium, and phosphorus. Results: One-hundred twenty patients (Group Thessaloniki = 60 patients, Group Rhodes = 60 patients) who were matched for demographic characteristics and type of thyroid disease and surgery were enrolled in our study. The sunshine levels were different between the two centers (Rhodes > Thessaloniki, p < 0.001). It was found that sunshine levels affect preoperative serum ionized calcium (p = 0.002) and postoperative parathyroid hormone levels (p = 0.025). Conclusions: Sunlight exposure levels may play a crucial role in preventing postoperative hypoparathyroidism. Patients living in locations with higher sunshine levels may have lower rates of postoperative hypoparathyroidism. Full article

Approximately 95% of skeletal size, bone, and muscle mass is achieved by the age of 18, with a rapid acceleration in bone mineral accumulation and muscle growth during the adolescent growth spurt. Bone mineral status in children and adolescents in Kazakhstan is a relevant subject for both clinical and fundamental research. The aim of this study was to investigate the prevalence of low bone mineral density (BMD) and the factors associated with it in children and adolescents living in the Abay region of Kazakhstan. The target group consisted of children and adolescents aged 5 to 17 years (n = 509) who had been residing in the Abay region of Kazakhstan since birth. Based on physiological age, participants were divided into two groups: 5–10 years (preschool and early school age) and 11–17 years (adolescence). All participants completed a questionnaire and underwent bone mineral density assessment using dual-energy X-ray absorptiometry (DXA). Comparisons were made between two age groups (5–10 and 11–17 years) and based on the presence or absence of reduced bone mineralization. Regression analysis identified four factors independently associated with reduced bone mineralization: ionized calcium (AOR 2099.9; p = 0.007), age (AOR 1.21; p = 0.013), body weight (AOR 0.97; p = 0.047), and green vegetables (AOR 0.46; p = 0.017). Conclusions: Our study demonstrated that 50.5% of children aged 5–10 years and 57.4% of adolescents aged 11–17 years had BMD below the age-specific norm. The study identified several risk factors that are associated with a decrease in BMD. These include blood ionized calcium, age, inadequate consumption of fruits and vegetables and dairy products, low physical activity, and insufficient sun exposure. These findings highlight the importance of early prevention of osteopenic conditions beginning in childhood and adolescence. Full article

Neuropathic pain, characterized by chronic allodynia, remains difficult to manage with current pharmacotherapies. Microglial activation plays a pivotal role in the development and maintenance of neuropathic pain and represents a promising therapeutic target. We previously demonstrated that Miyako Bidens pilosa extract powder (MBP), derived from Miyako Island, Okinawa, suppresses glial activation in a mouse model of amyotrophic lateral sclerosis. In this study, we investigated the analgesic potential of MBP in a mouse model of neuropathic pain. Neuropathic pain was induced in male ICR mice by partial sciatic nerve ligation (PSNL). Mice were orally administered MBP (2 g/kg) or vehicle daily. Mechanical allodynia was assessed using von Frey filaments. On postoperative day 7, MBP-treated mice exhibited significantly reduced allodynia compared to vehicle-treated mice. MBP also attenuated thermal hyperalgesia on postoperative day 7. Lumbar spinal cords (L5) were subjected to immunohistochemical analysis for ionized calcium-binding adaptor molecule 1 (Iba1), a microglial marker. MBP significantly decreased the number of Iba1-positive microglia in the ipsilateral dorsal horn. These results suggest that MBP alleviates neuropathic pain, at least in part, by suppressing microglial activation in the spinal cord. MBP may represent a novel plant-derived therapeutic candidate for treating neuropathic pain. Full article

Fish oil’s neuroprotective effects in ethanol-induced liver injury was investigated through the factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway. Male Wistar rats received a control liquid diet (C) or an ethanol diet (E), with 25% or 57% of fat replaced by fish oil (CF25, CF57, EF25, EF57) for 8 weeks. Compared to the C group, the E group exhibited brain damage, including impaired performance of Y maze and novel object recognition test, increased glial fibrillary acidic protein (GFAP)-positive astrocytes, and ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia. In the prefrontal cortex, glutathione (GSH) and phosphorylated (p)-NRF2 decreased, catalase activity increased, and nqo1 mRNA declined; hippocampal NRF2 and nqo1 were also downregulated. However, compared to the E group, the EF25 and EF57 groups exhibited restored spatial and memory functions, reduced GFAP and Iba-1 expressions, potentiated β-amyloid (Aβ) clearance, and escalated catalase activity. Furthermore, increases in p-NRF2 and elevated hippocampal nqo1 mRNA expressions in the prefrontal cortex were observed in the EF25 and EF57 groups. In conclusion, fish oil ameliorated deficits in spatial and memory functions, and enhanced Aβ1-42 clearance in the prefrontal cortex and hippocampus of rats with chronic ethanol-induced liver damage by activating the NRF2/KEAP1 pathway. Full article

Traumatic brain injury (TBI) induces complex molecular and cellular responses, often leading to vision deterioration and potential mortality. Current objective diagnostic methods are limited, necessitating the development of novel tools to assess disease severity. This review focuses on the retina, a readily approachable part of the central nervous system (CNS), as a potential indicator of TBI. We conduct a targeted database search and employ a blinded scoring system, incorporating both human and artificial intelligence (AI) assessments, to identify relevant articles. We then perform a detailed analysis to elucidate the molecular pathways and cellular changes in the retina following TBI. Recent findings highlight the involvement of key molecular markers, such as ionized calcium-binding adapter molecule 1 (IBA1), phosphorylated tau, glial fibrillary acidic protein (GFAP), and various cytokines (IL-1β, IL-6, and TNF). Additionally, the roles of oxidative stress, reactive oxygen species (ROS), and blood–retina barrier (BRB) disruption are explored. Based on these findings, we hypothesize that alterations in these molecular pathways and cellular components, particularly microglia, can serve as direct indicators of brain health and TBI severity. Recent technological advancements in retinal imaging now allow for a direct assessment of retinal cells, including microglia, and related inflammatory processes, facilitating the translation of these molecular findings into clinical practice. This review underscores the retina’s potential as a non-invasive window into the molecular pathophysiology of TBI. Full article

Background: The antidiabetic drug gliclazide is often taken with antacids due to its gastrointestinal side effects. However, patients rarely report antacid use, making drug–drug interactions a potential cause of therapy failure. Therefore, this study aimed to investigate the in vitro effects of various antacids on gliclazide permeability and to explore the underlying mechanisms. Methods: The permeability of gliclazide alone and in the presence of antacids (sodium bicarbonate, calcium carbonate, aluminum hydroxide, hydrotalcite and calcium carbonate/magnesium carbonate) was investigated using the parallel artificial membrane permeability assay (PAMPA) in four media (buffers pH 1.2, pH 4.5, pH 6.8 and water). The permeability coefficients were calculated, and the effect of pH on gliclazide permeability was also evaluated. Results: At simulated fasting gastric conditions (pH 1.2), groups with calcium carbonate, hydrotalcite and the combination of calcium carbonate/magnesium carbonate showed significantly higher permeability of gliclazide than the control group. At fed-state gastric conditions (pH 4.5), only hydrotalcite did not significantly change the permeability of gliclazide. Sodium bicarbonate, aluminum hydroxide and hydrotalcite significantly reduced the gliclazide permeability in comparison to the control group at pH 6.8 as a representative of fasted-state intestinal fluid. Conclusions: Antacids significantly impact the permeability of gliclazide at different pH values, potentially influencing its bioavailability. Gliclazide permeability is mainly influenced by pH-dependent ionization, though complex or salt formation may also play a role. Since both gliclazide and antacids are taken with food, and gliclazide is primarily absorbed in the small intestine, calcium- and magnesium-based antacids can be considered the most suitable choice. Full article

Gliomas, the most common type of primary brain tumor, are a significant cause of morbidity and mortality worldwide. Glioblastoma, a highly malignant subtype, is particularly common, aggressive, and resistant to treatment. The tumor microenvironment (TME) of gliomas, especially glioblastomas, is characterized by a distinct presence of tumor-associated macrophages (TAMs), which densely infiltrate glioblastomas, a hallmark of these tumors. This macrophage population comprises both tissue-resident microglia as well as macrophages derived from the walls of blood vessels and the blood stream. Ionized calcium-binding adapter molecule 1 (Iba1) and CD163 are established cellular markers that enable the identification and functional characterization of these cells within the TME. This review provides an in-depth examination of the roles of Iba1 and CD163 in malignant gliomas, with a focus on TAM activation, migration, and immunomodulatory functions. Additionally, we will discuss how recent advances in AI-enhanced cell identification and visualization techniques have begun to transform the analysis of TAMs, promising unprecedented precision in their characterization and providing new insights into their roles within the TME. Iba1 and CD163 appear to have both unique and shared roles in glioma pathobiology, and both have the potential to be targeted through different molecular and cellular mechanisms. We discuss the therapeutic potential of Iba1 and CD163 based on available preclinical (experimental) and clinical (human tissue-based) evidence. Full article

During the pregnancy and lactation phases, physiological adaptations occur in the mother to cope with the additional nutritional demands of the fetus and newborn. In experimental animals and cows, serotonin (5-HT) induces augmented bone mobilization by increasing calcium (Ca²⁺) concentrations in blood and milk during pregnancy and/or lactation. These interactions between 5-HT and Ca²⁺ homeostasis remain unknown in mares. Hence, the hypothesis of this study was that, as in other species, mares’ 5-HT and Ca²⁺ concentrations are influenced by pregnancy and lactation and that this relationship could be influenced by age. The aim was to verify the existence of a bidirectional interaction between circulating 5-HT and ionized (ICa²⁺) and total (TCa²⁺) Ca²⁺ shifts in thirty-one healthy lactating Spanish Purebred mares during pregnancy, evaluating the effect of different ages (<10- and >10 years old). Compared to >10-year-old mares, those aged <10 years old showed a greater 5-HT concentration from the 3rd to the 8th month of pregnancy (p < 0.05), a greater ICa²⁺ concentration from the 5th to the 8th month (p < 0.05), a lower TCa²⁺ concentration from the 1st to the 3rd month (p < 0.05), a greater concentration at the 7th, 8th, and 11th month (p < 0.05), and a greater ICa²⁺/TCa²⁺ ratio from the 5th to the 7th month (p < 0.05). The data obtained show an interesting and significant relationship between circulating 5-HT and both ICa²⁺ and TCa²⁺, as well as between ICa²⁺ and TCa²⁺. Moreover, aging appears to reduce the secretory tone of 5-HT, with a concurrent large shift in Ca²⁺ metabolism in lactating pregnant mares. Full article

Subclinical hypocalcemia negatively impacts dairy cows’ health, milk production, and reproduction, posing a global challenge. This study evaluated the effects of aluminum sulfate supplementation in the close-up diet to reduce blood phosphorus levels and prevent postpartum hypocalcemia. Thirty-four cows were assigned to the Control (CTRL, n = 17) and Treatment (TRT, n = 17) groups. The TRT group received 400 g/cow/day of aluminum sulfate at least 14 days before calving, with identical post-calving diets. Blood samples were analyzed for total and ionized calcium (tCa, iCa), phosphorus (P), magnesium (Mg), and beta-hydroxybutyrate (BHB). Milk yields were recorded. TRT cows had 0.22, 0.18, and 0.14 mmol/L higher tCa levels than CTRL cows at 12 h, 1 d, and 2 d postpartum, respectively, with elevated iCa levels from 10 days prepartum to 3 days postpartum. Lower serum P levels were observed in TRT cows until day 2 postpartum, while Mg levels remained similar. BHB levels differed only on day 14 postpartum. These findings suggest that aluminum sulfate supplementation effectively lowers serum P and increases tCa, offering a promising strategy for hypocalcemia prevention in dairy cows. Full article