Search Results (2,114)

Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl₃) in a rat model of MASH. The intervention with GdCl₃ effectively reduced KC markers CD68 and Clec4f, together with pro-inflammatory cytokines (IL-1β, TNFα, NOS2), without affecting anti-inflammatory markers (IL-10, MRC1). Histologically, GdCl₃ reduced hepatocyte ballooning and NAS despite persistent steatosis. KC depletion was associated with decreased oxidative stress markers (TBARS, 3-nitrotyrosine) and antioxidant enzyme activity (SOD, catalase). Additionally, markers of endoplasmic reticulum stress (ATF4, GRP78, CHOP, P58^IPK) and apoptosis (BAX/BCL2 ratio, cleaved caspase-3) were diminished. Despite these improvements, GdCl₃ had no effect on lipid or glucose metabolism in the liver, associated with persistent elevation of PTP1B expression induced by SRD intake. KC depletion, however, increased FGF21 expression. GdCl₃ treatment improved systemic insulin sensitivity and reduced fasting glucose and NEFA serum levels. In white adipose tissue, the treatment decreased adipocyte size, restored insulin signaling, and inhibited lipolysis (ATGL expression) without altering macrophage infiltration (IBA) or thermogenic protein levels (UCP1) in SRD rats. These findings suggest that KC depletion modulates liver-to-adipose tissue crosstalk, potentially through FGF21 signaling, contributing to improved systemic metabolic homeostasis of SRD animals. Full article

Type 2 diabetes mellitus (T2DM) is a multifactorial disorder defined by insulin resistance, β-cell dysfunction, and chronic hyperglycemia. Although peripheral mechanisms have been extensively studied, increasing evidence implicates the gastrointestinal tract in disease onset. Insights from bariatric surgery, gut hormone signaling, and incretin-based therapies suggest that the gut contributes actively beyond nutrient absorption. Yet, a cohesive framework integrating these observations remains absent, leaving a critical gap in our understanding of T2DM’s upstream pathophysiology. This work builds upon the anti-incretin theory, which posits that nutrient-stimulated neurohormonal signals—termed “anti-incretins”—arise from the proximal intestine to counteract incretin effects and regulate glycemic homeostasis. The excess of anti-incretin signals, perhaps stimulated by macronutrient composition or chemical additives of modern diets, disrupts this balance and may cause insulin resistance and β-cell depletion, leading to T2D. We hypothesize that the neuroendocrine signals produced by cholecystokinin (CCK)-I and secretin-S cells, both located in the proximal intestine, function as endogenous anti-incretins. In this context, we hypothesize a novel model centered on the chronic overstimulation of I and S cells by high-fat, high glycemic index modern diets. This drives what we term “amplified digestion”—a state marked by heightened vagal and hormonal stimulation of biliary and pancreatic secretions, increased enzymatic and bile acid activity, and alterations in bile acid composition. This condition leads to an extended breakdown of carbohydrates, lipids, and proteins into absorbable units, thereby promoting excessive nutrient absorption and ultimately contributing to insulin resistance and progressive β-cell failure. Multiple lines of clinical, surgical, and experimental evidence converge to support our model, rooted in the physiology of digestion and absorption. Western dietary patterns appear to induce an over-digestive adaptation—marked by excessive vagal and hormonal stimulation of biliary and pancreatic secretion—which amplifies digestive signaling. This heightened state correlates with increased nutrient absorption, insulin resistance, and β-cell dysfunction. Interventions that disrupt this maladaptive signaling—such as truncal vagotomy combined with duodenal bypass—may offer novel, physiology-based strategies for T2DM treatment. This hypothesis outlines a potential upstream contributor to insulin resistance and T2DM, grounded in digestive tract-derived neurohormonal dysregulation. This gut-centered model may provide insight into early, potentially reversible stages of the disease and identify a conceptual therapeutic target. Nonetheless, both the hypothesis and the accompanying surgical strategy—truncal vagotomy combined with proximal intestinal bypass—remain highly exploratory and require systematic validation through mechanistic and clinical studies. Further investigation is warranted to clarify the molecular regulation of I and S enteroendocrine cells, including the genetic and epigenetic factors that may drive hypersecretion. While speculative, interventions—surgical or pharmacologic—designed to modulate these digestive signals could represent a future avenue for research into T2DM prevention or remission, pending rigorous evidence. Full article

Zinc is an essential trace mineral for livestock, but excessive use can contribute to ecotoxicity and antimicrobial resistance. The objective of this study was to assess the impact of different zinc oxide (ZnO) levels in diets for weaned pigs on growth performance, mortality, dietary zinc flow, and environmental impacts. A 6-week feeding trial with 432 weaned pigs assessed three dietary treatments: high ZnO (pharmaceutical levels), intermediate ZnO, and low ZnO (EU recommendation). Growth performance for the growing–finishing period was modeled using the NRC (2012), and dietary Zn intake and fecal Zn excretion were estimated. Environmental impacts were analyzed via life cycle assessment (LCA) using SimaPro LCA software. High ZnO improved growth performance and reduced mortality (p < 0.05), but increased nursery fecal zinc excretion, resulting in a total fecal Zn excretion per pig of 54,125 mg, 59,485 mg, and 106,043 mg for low-, intermediate-, and high-ZnO treatments, respectively. In the nursery phase, high-ZnO treatment had the greatest impact on environmental footprint, increasing freshwater ecotoxicity and marine ecotoxicity indicators by 59.6% and 57.9%, respectively. However, high-ZnO-fed pigs had a greater body weight at the end of the nursery phase and were predicted to achieve a higher growth rate per 130 kg market pig, with fewer days to market and by sparing feed. Therefore, high-ZnO-fed pigs had reduced environmental burdens, including global warming potential, ozone depletion, land use, and mineral resource depletion. These findings demonstrate how livestock nutritionists can apply integrated modeling approaches to link animal performance with environmental outcomes within a One Health framework. Full article

This article investigates the formation of solidification cracks in steel forgings used for bearing rings in gear reducers of robotic arms. The forging and heat treatment processes, conducted under consistent technological conditions, revealed the occurrence of high-temperature annealing cracks caused by plasticity depletion during stress relaxation. Additionally, solidification cracks were analyzed, with chemical compositions and hardness measurements indicating susceptibility due to elevated carbon and chromium content, as well as a high cracking parameter. Die tool wear and damage during forging were identified as key contributors to crack formation, transferring surface defects, inclusions, and creating cracks that propagate during subsequent processing. The findings underscore the influence of the tooling conditions, material properties, and process parameters on the quality and reliability of steel forgings. Full article

Ensuring the safe reuse or discharge of treated wastewater is critical to achieving environmental sustainability, particularly in regions facing growing water stress. This study introduces a biological approach using Bacillus thuringiensis (Bt) biofilm formation as an indicator of treated wastewater quality from three wastewater treatment plants (WWTPs) in Deep East Texas. Treated wastewater samples were collected from chlorine and sulfur dioxide treatment stages at WWTPs in Nacogdoches, San Augustine, and San Jacinto counties. We assessed biofilm development through optical density and scanning electron microscopy (SEM) and evaluated changes in key anions (F⁻, Cl⁻, NO₂⁻, Br⁻, NO₃⁻, PO₄³⁻, and SO₄²⁻) using ion chromatography (IC). A two-tailed Student’s t-test was used to evaluate statistical significance (p ≤ 0.05). Remarkably, biofilm formation occurred in all samples, including those treated with chemical disinfectants, suggesting that microbial activity can still occur post-disinfection. Ion shifts, particularly the depletion of F⁻, NO₃⁻, and SO₄²⁻ and the release of Cl⁻, NO₂⁻, and PO₄³⁻, highlighted active microbial processes. These findings suggest that Bt biofilms can serve as sensitive, low-cost tools to monitor treated wastewater, offering critical insights into potential reuse risks and supporting more sustainable water management. Full article

Babesia divergens is a tick-borne apicomplexan parasite that causes human babesiosis, a malaria-like disease. B. divergens metabolism remains poorly characterized. Here, we employed a multiplatform mass spectrometry-based metabolomics approach (using CE-TOF/MS, GC-QTOF/MS, LC-QTOF/MS, and LC-QqQ/MS) to profile intra- and extracellular metabolic changes in B. divergens-infected and uninfected red blood cells (RBCs) and their supernatants. Our results indicate alterations in the metabolome caused by B. divergens infection and proliferation within RBCs. These findings are consistent with the major metabolic dependencies of B. divergens, including extracellular glucose, glutamine, and arginine, accompanied by the accumulation of glycolytic and TCA cycle intermediates. We identified altered nucleotide metabolism, pentose phosphate pathway activity, and redox imbalance. Depletion of lysoglycerophospholipids, glucose, arginine, and glutamine, and accumulation of free heme and sphingolipids suggested pathogenic effects. Growth experiments indicate that glucose and glutamine, but not hypoxanthine, are required for parasite growth. We additionally discovered a phosphorylated HEPES derivative (PEPES) produced upon B. divergens infection of RBCs in vitro. Collectively, these findings and their global interpretation provide insights into B. divergens metabolism and metabolic dependencies and host–parasite metabolic interactions and outline potential directions for future studies on human babesiosis diagnosis, prognosis assessment, and treatment. Full article

Background: Cervical cancer remains a major global health concern, with existing chemotherapy facing limited effectiveness owing to resistance. Polo-like kinase 1 (PLK1) overexpression in cervical cancer cells is a promising target for developing novel therapies to overcome chemoresistance and improve treatment efficacy. Methods: In this study, we developed a novel PROTAC, NC1, targeting PLK1 PBD via the N-end rule pathway. Results: This PROTAC effectively depleted the PLK1 protein in HeLa cells by inducing protein degradation. The crystal structure of the PBD-NC1 complex identified key PLK1 PBD binding interactions and isothermal titration calorimetry (ITC) confirmed a binding affinity of 6.06 µM between NC1 and PLK1 PBD. NC1 significantly decreased cell viability with an IC₅₀ of 5.23 µM, induced G2/M phase arrest, and triggered apoptosis in HeLa cells. In vivo, NC1 suppressed tumor growth in a HeLa xenograft mouse model. Conclusions: This research highlights the potential of N-degron-based PROTACs targeting the PLK1 protein in cancer therapies, highlighting their potential in future cervical anticancer treatment strategies. Full article

Turbot Scophthalmus maximus (Linnaeus, 1758) is one of the most valuable and economically important species for the Black Sea countries. In Bulgaria, their numbers are limited and stocks are depleted; therefore, monitoring development and health status is extremely important. Internal helminths are widespread among turbots on the Bulgarian Black Sea coast. However, description of this infection is relatively limited, and they have not been reported in scientific papers. For this purpose, a total of 36 hauls were made at depths from 15 to 90 m, and 65 turbots were examined for intestinal parasites. The present study represents the first report of internal helminths in turbot from Bulgarian marine waters through the spawning season, characterized morphologically based on a microscope observation and molecular identification. Evaluation of laboratory analyses revealed that two different parasites were determined: Bothriocephalus sp. (Müller, 1776) and Hysterothylacium aduncum (Rudolphi, 1802) and that 73.85% of the turbot were infected with one or more parasites. Based on the results, control measures and treatment for the wild population are unrealistic but should be considered for the containment and spread of diseases in aquaculture facilities. Full article

Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 10¹⁰ cells/human/day), low-dose live NB23 (1 × 10¹⁰ CFUs/human/day), or high-dose live NB23 (3 × 10¹⁰ CFUs/human/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. Full article

Ensuring bacterial safety of blood transfusions remains a critical focus in medicine. We investigated a novel pathogen reduction technology utilizing nylon functionalized with synthetic dyes (nylon affinity networks) to capture and remove bacteria from plasma. In the initial screening process, we spiked phosphate buffer solution (PBS) and human plasma (1 mL each) with 10 or 100 colony forming units (cfu) of either Escherichia coli or Staphylococcus epidermidis, exposed the suspensions to affinity networks and assessed the extent of bacterial reduction using agar plate cultures as the assay output. Nineteen synthetic dyes were tested. Among these, Alcian Blue exhibited the best performance with both bacterial strains in both PBS and plasma. Next, bacterial suspensions of approximately 1 and 2 cfu/mL in 10 and 50 mL, respectively, were treated with Alcian Blue affinity networks in three sequential capture steps. This procedure resulted in complete bacterial depletion, as demonstrated by the lack of bacterial growth in the remaining fraction. The viability of the captured bacteria was confirmed by plating the post-treatment affinity networks on agar. Alcian Blue affinity networks captured and sequestered a few plasma proteins identified by liquid chromatography tandem mass spectrometry. These findings support the potential applicability of nylon affinity networks to enhance transfusion safety, although additional investigations are needed. Full article

Eutrophication has become the primary water quality issue for most of the freshwater and coastal marine ecosystems in the world. Caused by excessive nitrogen (N) and phosphorus (P) inputs, it has a significant impact on aquatic ecosystems, resulting in algal blooms, oxygen depletion, and biodiversity loss. Zeolites have been identified as effective adsorbents for removal of these pollutants, improving water quality and ecosystem health. Kinetic and isotherm adsorption experiments were conducted to examine the adsorption efficiency of four zeolites of various origins (Greek, Slovakian, Turkish, and Bulgarian) and a specific modification (ZeoPhos) to determine the most effective material for N and P removal. The aim of the study is to discover the best zeolite for chemical adsorption in eutrophic waters by comparing their adsorption capacities and pollutant removal efficiencies along with SEM, TEM, and X-RD spectrographs. Slovakian ZeoPhos has been identified as the best-performing material for long-term and efficient water treatment systems for eutrophication management. Full article

Although acetaminophen (APAP) overdose represents the predominant cause of drug-induced acute liver failure (ALF) worldwide and has been extensively studied, the modes of cell death remain debatable and the treatment approach for APAP-induced acute liver failure is still limited. This study investigated the mechanisms of APAP hepatotoxicity in primary mouse hepatocytes (PMHs) by using integrated methods (MTT assay, HPLC analysis for glutathione (GSH), Calcein-AM for labile iron pool detection, confocal microscopy for lipid peroxidation and mitochondrial superoxide measurements, electron microscopy observation, and Western blot analysis for ferritin), focusing on the role of iron dysregulation under oxidative stress. Our results showed that 20 mM APAP treatment induced characteristic features of ferroptosis, including GSH depletion, mitochondrial dysfunction, and iron-dependent lipid peroxidation. Further results showed significant ferritin degradation and subsequent iron releasing. Iron chelator deferoxamine (DFO) and N-acetylcysteine (NAC) could alleviate APAP-induced hepatotoxicity, while autophagy inhibitors did not provide a protective effect. In vitro experiments confirmed that hydrogen peroxide directly damaged ferritin structure, leading to iron releasing, which may aggravate iron-dependent lipid peroxidation. These findings provide evidence that APAP hepatotoxicity involves a self-amplifying cycle of oxidative stress and iron-mediated oxidative damaging, with ferritin destruction playing a key role as a free iron source. This study offers new insights into APAP-induced liver injury beyond conventional cell death classifications, and highlights iron chelation as a potential therapeutic strategy alongside traditional antioxidative treatment with NAC. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

In many developing African countries, milk safety is often managed through traditional methods such as fermentation or boiling over firewood. While these approaches reduce some microbial risks, they present critical limitations. Firewood dependency contributes to deforestation, depletion of agricultural residues, and loss of soil fertility, which, in turn, compromise environmental health and food security. Solar pasteurization provides a reliable and sustainable method for thermally inactivating pathogenic microorganisms in milk and other perishable foods at sub-boiling temperatures, preserving its nutritional quality. This study aimed to evaluate the thermal and microbial performance of a low-cost solar milk pasteurization system, hypothesized to effectively reduce microbial contaminants and retain milk quality under natural sunlight. The system was constructed using locally available materials and tailored to the climatic conditions of the Savanna ecological zone in West Africa. A flat-plate glass solar collector was integrated with a 0.15 cm thick stainless steel cylindrical milk vat, featuring a 2.2 cm hot water jacket and 0.5 cm thick aluminum foil insulation. The system was tested in Navrongo, Ghana, under ambient temperatures ranging from 30 °C to 43 °C. The pasteurizer successfully processed up to 8 L of milk per batch, achieving a maximum milk temperature of 74 °C by 14:00 GMT. Microbial analysis revealed a significant reduction in bacterial load, from 6.6 × 10⁶ CFU/mL to 1.0 × 10² CFU/mL, with complete elimination of coliforms. These results confirmed the device’s effectiveness in achieving safe pasteurization levels. The findings demonstrate that this locally built solar pasteurization system is a viable and cost-effective solution for improving milk safety in arid, electricity-limited regions. Its potential scalability also opens avenues for rural entrepreneurship in solar-powered food and water treatment technologies. 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