Search Results (115)

Parabens—specifically methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP)—are widely used substances in everyday life, particularly as preservatives in pharmaceutical and food products. However, these compounds are not effectively removed by conventional water and wastewater treatment processes, potentially causing disruptions to human homeostasis and the endocrine system. This study conducted a transport and dimensional analysis through simulation of the adsorption process for these parabens, using zinc chloride-activated carbon derived from spent coffee grounds (ACZnCl₂) as the adsorbent, implemented via Aspen Properties^® and Aspen Adsorption^®. Simulations were performed for two inlet concentrations (50 mg/L and 100 mg/L) and two adsorption column heights (3 m and 4 m), considering a volumetric flow rate representative of a medium-sized city with approximately 100,000 inhabitants. The results showed that both density and surface tension of the parabens varied linearly with increasing temperature, and viscosity exhibited a marked reduction above 30 °C. Among the tested conditions, the configuration with 50 mg∙L⁻¹ inlet concentration and a 4 m column height demonstrated the highest adsorption capacity and better performance under adsorption–desorption equilibrium. These findings indicate that the implementation of adsorption beds on an industrial scale in water and wastewater treatment systems is both environmentally and socially viable. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

The transition from conchocelis to conchosporangia in Pyropia haitanensis represents a pivotal stage in its life cycle. As a commercially vital red alga, P. haitanensis plays a dominant role in global nori production. The transition governing its sporulation efficiency is pivotal for aquaculture success, yet the underlying regulatory mechanisms, especially their integration with metabolic cues such as polyamines, remain poorly understood. This study uncovered a critical role for the polyamine spermine (SPM) in promoting conchosporangial formation, mediated through the signaling activity of superoxide anions (O₂·⁻). Treatment with SPM markedly elevated O₂·⁻ levels, an effect that was effectively inhibited by the NADPH oxidase inhibitor diphenyliodonium chloride (DPI), underscoring the role of O₂·⁻ as a key signaling molecule. Transcriptomic analysis revealed that SPM enhanced photosynthesis, carbon assimilation, and respiratory metabolism, while simultaneously activating antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), to regulate hydrogen peroxide (H₂O₂) levels and maintain redox homeostasis. Furthermore, SPM upregulated genes associated with photosynthetic carbon fixation and the C₂ oxidative photorespiration pathway, supplying the energy and metabolic resources necessary for this developmental transition. These findings suggested that SPM orchestrated O₂·⁻ signaling, photosynthetic activity, and antioxidant defenses to facilitate the transition from conchocelis to conchosporangia in P. haitanensis. Full article

Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid–base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia—often iatrogenic—may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride’s role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome. Full article

The GABA_A receptors, through a short-term interaction with a mediator, induce hyperpolarization of the membrane potential (V_m) via the passive influx of chloride ions (Cl⁻) into neurons. The massive (or intense) activation of the GABA_ARs by the agonist could potentially lead to depolarization/excitation of the V_m. Although the ionic mechanisms of GABA_A-mediated depolarization remain incompletely understood, a combination of the outward chloride current and the inward bicarbonate current and the resulting pH shift are the main reasons for this event. The GABA_A responses are determined by the ionic gradients—neuronal pH/bicarbonate homeostasis is maintained by carbonic anhydrase and electroneutral/electrogenic bicarbonate transporters and the chloride level is maintained by secondary active cation–chloride cotransporters. Massive activation can also induce the rundown effect of the receptor function. This rundown effect partly involves phosphorylation, Ca²⁺ and the processes of receptor desensitization. In addition, by various methods (including fluorescence and optical genetic methods), it has been shown that massive activation of GABA_ARs during pathophysiological activity is also associated with an increase in [Cl⁻]_i and a decline in the pH and ATP levels in neurons. Although the relationship between the neuronal changes induced by massive activation of GABAergic signaling and the risk of developing neurodegenerative disease has been extensively studied, the molecular determinants of this process remain somewhat mysterious. The aim of this review is to summarize the data on the relationship between the massive activation of inhibitory signaling and the ionic changes in neurons. The potential role of receptor dysfunction during massive activation and the resulting ionic and metabolic disruption in neurons during the manifestation of network/seizure activity will be considered. Full article

Serious enteric disease caused by seven species of Eimeira continues to cause significant economic damage to the poultry industry. E. acervulina is one of the most widespread strains in farms and has a significant impact on chicken weight loss. Currently, the use of anticoccidial agents to suppress the occurrence of coccidiosis in farms is considerably restricted due to public health and environmental pollution issues. It is important to understand the protective immunity of the host against Eimeria infections with regard to natural products that could be used as alternatives to anticoccidial agents. Berberine chloride is known for its various biological functions, including its anti-parasite activity. However, its impact on intestinal morphology and immune-related activity in broilers infected with Eimeria still remains unclear. The aim of this study is to evaluate the anticoccidial effects of a berberine-based diet in broilers infected with E. acervulina and to monitor the host immune phenomenon using transcriptomic analysis. Administration of berberine to chickens infected with E. acervulina significantly reduced fecal oocyst production and intestinal lesion scores, and increased duodenal villus height, indicating anticoccidial activity and positive effects on intestinal morphology. Transcriptomic analysis of chickens infected with E. acervulina generally observed the down-regulation of metabolism-related genes and the up-regulation of cell integrity-related genes at day 4 post-infection. At day 6 post-infection, an increase in immune-related genes and cellular-homeostasis-related genes was generally observed. Berberine-treated and E. acervulina-infected chickens showed cytokine-cytokine receptor interaction in the second term in a Kyoto Encyclopedia of Genes and Genomes pathway analysis at day 4 post-infection, but not in chickens infected with E. acervulina alone, suggesting host immune changes induced by berberine. These results suggest that berberine, which exhibits anticoccidial effects, may have therapeutic and/or prophylactic potential in protecting the host from infectious and economic-loss-causing diseases, such as Eimeria infection. Full article

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. Pseudomonas aeruginosa is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. P. aeruginosa exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, P. aeruginosa undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic P. aeruginosa infections in CF. Full article

Aluminum (Al) is one of the most abundant metals on Earth and is well known as an environmental neurotoxic agent in the pathogenesis of Alzheimer’s disease. Aluminum toxicity is associated with oxidative stress, reduction of antioxidant enzymes, and disruption of the balance of cellular metals, such as iron (Fe), calcium (Ca), and copper (Cu), which causes structural and functional changes in the nervous tissue of the brain or peripheral nervous system. The intake of functional foods, rich in antioxidants, such as quercetin, may be beneficial in combating oxidative stress and neurodegenerative changes in the brain. The aim of this study was to provide deeper insight into the cellular and molecular neuroprotective effects of quercetin in regulating amyloid-beta (Aβ) accumulation, tau pathology, and neuroinflammation in the Al/D-galactose-induced rat model (Al/D-gal) of AD. The results showed that quercetin successfully modulated the impaired homeostatic and neuropathological consequences of aluminum chloride and D-galactose administration over 28 days: it directly protected neurons by regulating the level of oxidative stress and antioxidants, reduced Aβ aggregation by inhibiting the activity of acetylcholinesterase (AChE), increased the survival, growth, and differentiation of nerve cells by maintaining the level of brain-derived neurotrophic factor (BDNF), and regulated microglial immunoreactivity and neuroinflammation by reducing the level of proinflammatory cytokines. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in reducing Al-induced neurotoxicity and maintaining adaptive homeostasis, which consequently affects the functioning of the central nervous system and the whole organism. Full article

This study evaluated the response of two willow varieties, Salix × smithiana Willd. and Salix viminalis L. var. Gigantea, to selected heavy metals and elevated soil salinity, simulating complex environmental conditions during phytoremediation. Plants propagated from stem cuttings were cultivated in pots under field conditions in soil artificially contaminated with a mixture of Cd, Ni, Cu, Zn, and Pb salts at two concentration levels representing lower and higher guideline thresholds. Sodium chloride was added to induce salinity stress. S. × smithiana exhibited enhanced growth under combined metal and salinity stress, suggesting efficient tolerance mechanisms. This was reflected in elevated relative water content (RWC) and increased accumulation of Zn and Cd in shoots. In contrast, Gigantea showed growth inhibition and primarily sequestered metals in roots, indicating a stress-avoidance strategy and reduced metal translocation. While salinity alone negatively affected both varieties, its combination with metals mitigated growth reduction in S. × smithiana, possibly due to improved ion homeostasis or cross-tolerance. Zn and Cd displayed the highest bioconcentration and mobility. Based on bioconcentration factor (BCF) and translocation factor (TF), S. × smithiana appears suitable for phytoextraction, whereas S. viminalis var. Gigantea appears suitable for phytostabilization. These results support species-specific approaches to phytoremediation in multi-contaminant environments. Full article

Nitrite and carbon dioxide (CO₂) are common environmental substances in intensive aquaculture ponds. However, the effects and mechanisms of their combined exposure on aquatic animals remain unclear. In this study, we investigated the toxic effects of 2.5, 5, and 10 mg/L CO₂ in the presence of 2 mg/L nitrite on hematological, blood gas parameters, and liver physiological and pathological changes in zebrafish (Danio rerio) over 14 days and 28 days. Our results demonstrated a reduced nitrite uptake and accumulation in the gills and liver of zebrafish exposed to nitrite and varying levels of CO₂. Increased CO₂ levels also led to a decrease in the expression of gill ae1, whereas the transcriptional levels of nhe1 and nhe3b, nkcc and nbc1 were notably upregulated. Moreover, there was a decrease in Cl⁻ and Na⁺ concentrations, along with an increase in K⁺ concentrations. These changes suggested that zebrafish responded to increased CO₂ stress by reducing their absorption of chloride-dependent nitrite, excreting H⁺ and maintaining their internal pH. Exposure to higher CO₂ levels in the presence of nitrite resulted in lower blood MetHb levels and liver oxidative stress compared to the nitrite single-exposure treatment. Furthermore, co-treatment with CO₂ and nitrite attenuated the nitrite-induced damage to genes related to mitochondrial respiratory chain function (ndufs1, mtnd5, mtycb, atp5f1b, mtatp8), leading to elevated ATP levels. Exposure to nitrite alone increased the expression of lipolytic genes (hsla, cpt1aa, atgl) and decreased the expression of lipid synthesis genes (fasn, acaca), resulting in a decrease in TG and TC content in zebrafish liver. However, co-treatment with CO₂ and nitrite prevented the nitrite-induced disruption of lipid metabolism, as evidenced by the improvement in TG and TC levels, as well as transcriptional levels of lipid metabolism-related genes. In conclusion, our study suggests that in the presence of 2 mg/L nitrite, increased CO₂ (2.5–10 mg/L) may modulate ion transporter genes to reduce the chloride-dependent nitrite uptake and maintain pH homeostasis, concurrently alleviating oxidative stress, restoring mitochondrial respiratory function, and improving lipid metabolism in a dose-dependent manner. These changes may be related to the increase in the concentration of bicarbonate ions in the water as the CO₂ level rises. These findings shed light on the potential protective effects of CO₂ in mitigating the harmful effects of nitrite exposure in aquatic animals. Full article

Mammalian spermatozoa undergo a series of physiological and biochemical changes in the oviduct that lead them to acquire the ability to fertilize eggs. During their transit in the oviduct, spermatozoa face a series of environmental changes that can affect sperm viability. A series of ion channels and transporters, as well as the sperm cytoskeleton, allow spermatozoa to remain viable and functional. Cl⁻ channels such as TMEM16A (calcium-activated chloride channel), CFTR (cystic fibrosis transmembrane conductance regulator), and ClC3 (chloride voltage-gated channel 3) are some of the ion transporters involved in maintaining cellular homeostasis. They are expressed in mammalian spermatozoa and are associated with capacitation, acrosomal reaction, and motility. However, little is known about their role in maintaining sperm volume. Therefore, this study aimed to determine the mechanism through which TMEM16A maintains sperm volume during capacitation. The effects of TMEM16A were compared to those of CFTR and ClC3. Spermatozoa were capacitated in the presence of specific TMEM16A, CFTR, and ClC3 inhibitors, and the results showed that only TMEM16A inhibition increased acrosomal volume, leading to changes within the acrosome. Similarly, only TMEM16A inhibition prevented actin polymerization during capacitation. Further analysis showed that TMEM16A inhibition also prevented ERK1/2 and RhoA activation. On the other hand, TMEM16A and CFTR inhibition affected both capacitation and spontaneous acrosomal reaction, whereas ClC3 inhibition only affected the spontaneous acrosomal reaction. In conclusion, during capacitation, TMEM16A activity regulates acrosomal structure through actin polymerization and by regulating ERK1/2 and RhoA activities. Full article

Polycystic kidney disease (PKD) is the most common hereditary disorder that disrupts renal function and frequently progresses to end-stage renal disease. Recent advances have elucidated the critical role of primary cilia and ciliary ion channels, including transient receptor potential (TRP) channels, cystic fibrosis transmembrane conductance regulator (CFTR), and polycystin channels, in the pathogenesis of PKD. While some channels primarily function as chloride conductance channels (e.g., CFTR), others primarily regulate calcium (Ca⁺²) homeostasis. These ion channels are essential for cellular signaling and maintaining the normal kidney architecture. Dysregulation of these pathways due to genetic mutations in PKD1 and PKD2 leads to disrupted Ca⁺² and cAMP signaling, aberrant fluid secretion, and uncontrolled cellular proliferation, resulting in tubular cystogenesis. Understanding the molecular mechanisms underlying these dysfunctions has opened the door for innovative therapeutic strategies, including TRPV4 activators, CFTR inhibitors, and calcimimetics, to mitigate cyst growth and preserve renal function. This review summarizes the current knowledge on the roles of ciliary ion channels in PKD pathophysiology, highlights therapeutic interventions targeting these channels, and identifies future research directions for improving patient outcomes. Full article

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury and strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines microglial responses to chemical hypoxia induced by cobalt chloride (CoCl₂) in BV-2 murine microglial cells, focusing on signaling pathways and proteomic alterations. We assessed the protective effects of monoclonal antibodies against TNFα and IL-1β. CoCl₂ exposure led to decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, and activation of inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, and NF-κB/NLRP3. These responses were significantly mitigated by treatment with anti-TNFα and anti-IL-1β, suggesting their dual role in reducing microglial damage and inhibiting inflammatory reactivity. Additionally, these treatments reduced apoptosis by modulating ATF4 and the p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics and Gene Ontology revealed that CoCl₂ exposure led to the upregulation of proteins primarily involved in endoplasmic reticulum and catabolic processes, while downregulated proteins are associated with biosynthesis. Anti-TNFα and anti-IL-1β treatments partially restored the proteomic profile toward normalcy, with network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator in recovery. These findings offer insights into the pathogenesis of hypoxic microglial impairment and suggest potential therapeutic targets. Full article

Rising soil salinity poses significant challenges to Mediterranean viticulture. While some rootstocks effectively reduce salt accumulation in grafted scions, the mechanisms and performance of novel rootstocks remain largely unexplored. This study compared two novel M-series rootstocks (M2, M4) with established commercial rootstocks (1103 Paulsen, R110) to evaluate their physiological responses and salt tolerance under irrigation with varying salinity levels (0, 25, 50, and 75 mM NaCl) over 5 months. Growth parameters, photosynthetic efficiency, chlorophyll content (SPAD), ion homeostasis, and visual symptoms were monitored. Results revealed genotype-specific strategies: 1103 Paulsen exhibited robust photosynthetic efficiency and ion exclusion, maintaining growth and chlorophyll stability; M2 demonstrated superior biomass retention and moderate ion compartmentalization but showed reduced photosynthetic performance at higher salinity levels; R110 displayed effective ion management at moderate salinity but experienced significant growth reduction under severe stress; and M4 was the most sensitive, with severe reductions in growth and ion homeostasis. Organ-specific responses highlighted roots acting as primary ion reservoirs, particularly for sodium and calcium; leaves exhibited high potassium and chloride concentrations, critical for photosynthesis but prone to ionic imbalance under stress; and stems and wood played a buffering role, compartmentalizing excess sodium and minimizing damage to photosynthetic tissues. The reported findings provide valuable insights for rootstock selection and breeding programs, particularly for regions facing increasing soil and water salinization challenges. Full article

Coronavirus disease 2019 (COVID-19) causes pulmonary edema, which disrupts the lung alveoli–capillary barrier and leads to pulmonary cell apoptosis, the main cause of death. However, the molecular mechanism behind SARS-CoV-2’s apoptotic activity remains unknown. Here, we revealed that SARS-CoV-2-ORF-3a mediates the pulmonary pathology associated with SARS-CoV-2, which is demonstrated by the fact that it causes lung tissue damage. The in vitro results showed that SARS-CoV-2-ORF-3a triggers cell death via the disruption of mitochondrial homeostasis, which is modulated through the regulation of Mitochondrial ATP-sensitive Potassium Channel (MitoK^ATP). The addition of exogenous Potassium (K⁺) in the form of potassium chloride (KCl) attenuated mitochondrial apoptosis along with the inflammatory interferon response (IFN-β) triggered by SARS-ORF-3a. The addition of exogenous K⁺ strongly suggests that dysregulation of K⁺ ion channel function is the central mechanism underlying the mitochondrial dysfunction and stress response induced by SARS-CoV-2-ORF-3a. Our results designate that targeting the potassium channel or its interactions with ORF-3a may represent a promising therapeutic strategy to mitigate the damaging effects of infection with SARS-CoV-2. Full article