Search Results (40)

Recent breakthroughs in cancer immunotherapy have shown remarkable success, yet treatment efficacy varies significantly among individuals. Emerging evidence highlights the gut microbiota as a key modulator of immunotherapy response, while vitamin D (VD), an immunomodulatory hormone, has garnered increasing attention for its potential interactions with gut microbiota and immunotherapy outcomes. However, the precise mechanisms and clinical applications of VD in this context remain controversial. This study systematically analyzed peer-reviewed evidence from PubMed, Scopus, Web of Science, PsycINFO, and MEDLINE (January 2000–May 2025) to investigate the complex interplay among VD, gut microbiota, and cancer immunotherapy. This review demonstrates that VD exerts dual immunomodulatory effects by directly activating immune cells through vitamin D receptor (VDR) signaling while simultaneously reshaping gut microbial composition to enhance antitumor immunity. Clinical data reveal paradoxical outcomes: optimal VD levels correlate with improved immunotherapy responses and reduced toxicity in some studies yet are associated with immunosuppression and poorer survival in others. The bidirectional VD–microbiota interaction further complicates this relationship: VD supplementation enriches beneficial bacteria, which reciprocally regulate VD metabolism and amplify immune responses, whereas excessive VD intake may disrupt this balance, leading to dysbiosis and compromised therapeutic efficacy. These findings underscore the need to elucidate VD’s dose-dependent and microbiota-mediated mechanisms to optimize its clinical application in immunotherapy regimens. Future research should prioritize mechanistic studies of VD’s immunoregulatory pathways, personalized strategies accounting for host–microbiota variability, and large-scale clinical trials to validate VD’s role as an adjuvant in precision immunotherapy. Full article

The ozonation of norfloxacin (NOF), a widely used fluoroquinolone antibiotic, in the presence of Na⁺, Fe²⁺, Cu²⁺, Ni²⁺, and Co²⁺ cations and their montmorillonite-supported counterparts was investigated. The NOF degradation and the toxicity of the ozonized mixtures towards an aquatic organism (Lemna minor) were evaluated in terms of changes in its frond number, chlorophyll content, photosynthesis efficacy, and production of reactive oxygen species (ROS). The evolution over time of the NOF degradation grade and the toxicity were discussed in terms of i. the observed changes in the interactions of the cation and clay catalyst with NOF molecules; ii. the pH decay, during ozonation. Ion-exchange and Lewis acid–base interactions appear to govern NOF adsorption and clay catalyst dispersion in correlation with the progressive formation of acidic species in the aqueous media. These findings reveal promising prospects for tailoring optimum oxidative water treatments with minimum toxicity and for predicting their environmental impacts on aquatic media. Full article

Vitamin D is a sterol prohormone with no intrinsic biological activity. Calcitriol, the active form of vitamin D, is synthesized in the kidneys. It has well-known pleiotropic and cytoprotective properties. In addition to regulating parathyroid hormone secretion and enhancing gut calcium absorption, it exhibits antioxidant, anti-inflammatory, antiproliferative, and antineoplastic effects. However, the role of vitamin D in AKI is unclear, unlike in CKD. Thus, this review aimed to understand how dysregulated vitamin D homeostasis occurs in AKI, as well as to explore how vitamin D deficiency and excess influence AKI. A comprehensive literature search was conducted between January 2000 and June 2024 to uncover relevant works detailing vitamin D homeostasis in health as well as investigating the impact of vitamin D deficiency and excess in humans, animals, and in vitro cell models of AKI. According to the findings of this review, vitamin D appears to have a reciprocal relationship with AKI. Acute renal injury, among other factors, can cause hypo- or hypervitaminosis D. Conversely, AKI can also be caused by vitamin D deficiency and toxicity. Even though hypovitaminosis D is associated with AKI, it is uncertain how it impacts AKI outcomes in distinct clinical scenarios. Newer therapeutic options might emerge as a result of understanding these challenges. Vitamin D supplementation may ameliorate renal injury but needs further validation. Furthermore, hypervitaminosis D has also been implicated in AKI by causing hypercalcemia and hyperphosphatemia. It is crucial to avoid prolonged, uncontrolled, and unsupervised supraphysiological vitamin D administration, especially intramuscular injection. Full article

Plant growth and its interaction with microorganisms change yearly. High temperature and humidity have characterized recent seasons in the north of Italy and around the world, increasing the parasitic ability of Aspergillus flavus to colonize maize kernels and aflatoxin levels. These molecules have the highest acute and chronic toxicity of all mycotoxins; the maximal concentration in agricultural food and feed products, and their commodities, are regulated worldwide. In this study we suggest a simple methodology to test the susceptibility of candidate maize varieties to A. flavus before their release onto the market. A panel of 92 inbred lines and 14 hybrids were analysed, disease phenotypes were scored on artificially inoculated kernels using a rolled towel assay, and therefore we observed different responses to fungal infection on the kernels, outlining a high variability among the tested lines characterized by a different effect of the pathogen on seedling development. Even the hybrids responded differently on a statistical basis to A. flavus with regard to the development of coleoptile, allowing their categorization into classes of susceptibility to be used for the varietal registration. Interestingly, the hybrid 6a-A was less susceptible to A. flavus compared to its reciprocal in terms of the length of the coleoptile. The comparison of breeding lines released on the market in different years suggested a poor improvement in genetic resistance against A. flavus in maize so far, opening up a possible topic for future research aimed at mitigating the impact of climate change on agriculture. Full article

The aim of this study was to evaluate the influence of scion/rootstock genotypes on ionic toxicity, oxidative damage, and photosynthesis in cashew plants subjected to salt stress. Scion/rootstock combinations (CCP 76/CCP 76, CCP 76/CCP 09, CCP 09/CCP 09 and CCP 09/CCP 76) were obtained by reciprocal grafting between two genotypes (CCP 76 and CCP 09) of dwarf cashew and subjected to increased NaCl (0, 50 and 100 mM) for 30 days. Plants with CCP 76 scions had higher leaf fresh weights compared to plants with CCP 09 scions in both moderate (50 mM)- and high (100 mM)-salinity conditions. Under moderate levels of salinity, CCP 76 scions showed lower stomatal conductance, which is associated with weaker leaf toxicity symptoms, as well as lower Na⁺ content and higher K⁺ content in the leaves. Thus, the better foliar exclusion of Na⁺ by CCP 76 scions can be attributed to greater stomatal control, which allows for better growth and sufficient foliar K⁺ nutrition to mitigate foliar toxicity. Under high levels of salinity, a reduction in net photosynthesis occurred in all scion/rootstock combinations, which was apparently due to stomatal and non-stomatal restrictions. The activities of the oxidative enzymes (superoxide dismutase—SOD; ascorbate peroxidase—APX; and phenol peroxidase—POD) were little influenced by salinity, while there was a significant increase in the non-enzymatic antioxidants ascorbate (AsA) and glutathione (GSH). In addition, a reduction in photochemical activity was observed under saline conditions, suggesting that photosystems possess a potential protective mechanism. It was observed that the stomatal closure exhibited by the CCP 76 scion genotype may exert relative control over the flow of Na⁺ to the shoots under salt stress conditions. Taken together, the data show that, in the two genotypes evaluated, oxidative protection was more associated with reduced photochemical activity and higher levels of non-enzymatic antioxidants (AsA and GSH) than it was with the SOD-APX-POD enzymatic system. Full article

Background/Objectives: Tacrine is a centrally active non-competitive reversible acetylcholinesterase inhibitor. It also exerts antagonising activity against N-methyl-D-aspartate receptors. Tacrine was approved for the treatment of Alzheimer’s disease in 1993, but was withdrawn from clinical use in 2013 because of its hepatotoxicity and gastrointestinal side effects. Nevertheless, tacrine is currently facing a renewed wave of interest primarily due to several new tacrine-incorporated hybrids and derivates. There were two specific aims for this study: firstly, to explain the mechanisms of the adverse action of tacrine, as a distinctive example of a highly effective acetylcholinesterase inhibitor; and secondly to check whether luminal impedance planimetry is feasible for preclinical testing of possible side effects of compounds potentially toxic to the gastrointestinal tract. Methods: Six experimental pigs were used as the animal model in this study. Five major parameters were evaluated: luminal pressure (mmHg), estimated diameter (mm), cross-sectional area (mm²), distensibility (mm²/mmHg), and zone compliance (mm³/mmHg). All measurements were performed before and 360 min after intragastric administration of 200 mg tacrine (at the porcine tacrine T_max). Results: This study consistently demonstrated an increase in luminal pressure (a directly measured indicator) for the particular balloon filling volumes used, and inversely a reciprocal decrease in the other parameters after tacrine administration. Conclusions: Endoscopic luminal impedance planimetry is a feasible method to evaluate functional response of the lower oesophageal sphincter to tacrine in experimental pigs. Tacrine did not compromise the function of the lower oesophageal sphincter either toward oesophageal spasms or, in contrast, decreased competence of the lower oesophageal sphincter. Full article

Several types of contaminants are anthropogenically introduced into natural aquatic ecosystems and interact with other chemicals and/or with living organisms. Although metal toxicity alone has been relatively well studied, the toxic metal ion effects in the mixture have been thoroughly studied only during the last decades. This review focuses on the published reciprocal effects of different metals on different species of algae, together with describing their toxic effects on studied parameters. Phytoplankton as a bioindicator can help to estimate the reciprocal metal risk factor. Many methodologies have been developed and explored, such as the biotic ligand model (BLM), concentration addition (CA), independent action (IA), sensitivity distribution of EC50 species sensitivity distribution (SSD curves), and others, to study reciprocal metal toxicity and provide promising results, which are briefly mentioned too. From our review, we can commonly conclude the following: Zn acted antagonistically with most heavy metals (Al, Cu, Cd, and Ni). The Cu interaction with Cd, Fe, and Pb was mostly antagonistic. Cd showed synergistic behaviour with Hg, Cu, Zn, and Pb and antagonistic behaviour with Co and Fe in many cases. Methods and techniques need to be developed and optimised to determine reciprocal metal toxicity so that the ecotoxicological predictions made by using phytoplankton can be more accurate and related to real-time toxic metals risks to the aquatic ecosystem. This is the main objective of ecotoxicological tests for risk assessment. Understanding how metals enter algal cells and organelles can help to solve this challenge and was one of the main parts of the review. Full article

Electroless nickel-boron coatings present outstanding properties such as high hardness, excellent wear resistance and uniform coating, and thus they are considered to be alternative to toxic hard chrome coatings. However, they contain lead that is toxic and used as stabilizer in the plating bath. This study aims to investigate the tribocorrosion behaviour of lead-free electroless nickel-boron coatings. In the present research, several tests were carried out to investigate the behaviour of these coatings under both dry and tribocorrosion reciprocating sliding wear against alumina balls, at room temperature. The open circuit potential (OCP) method was used to determine the degradation mechanism of the coatings. The results of the tribocorrosion and dry wear tests showed that the performance of coatings was very different from each other. A steady state for the coefficient of friction (COF) is achieved during the tribocorrosion test, whereas the constant production of debris and their presence in the contact implied an increase in COF with distance during the dry wear test. The wear mechanisms of these coatings also presented variations in these tests. It was found that the wear area calculated from tribocorrosion is lower (56 µm²) than the one from dry sliding test (86 µm²). Full article

This article presents the influence of ecological measures, i.e., the addition of effective microorganisms and silver compounds to lubricating oil, on the operating parameters of an internal combustion engine. The basic diagnostic parameters of a reciprocating engine that determine its technical condition are described. In the Materials and Methods section, the research stand and materials are presented. The main section of the article presents a comparison of pure oil and oil with the addition of effective microorganisms and silver compounds. It was found that the addition of effective microorganisms and silver compounds to oil reduces the emission of toxic components into the atmosphere with exhaust gas, and the other engine operation parameters for each load value indicate that these additives do not cause deterioration in the technical condition of the tested engine. Of all the agents used, the addition of ceramic tubes gives the best results, as it is an additive that does not affect the properties of the oil in its composition. The advantage of ceramic tubes is the slow release of effective microorganisms, which has an impact on the oil’s performance, and thus on engine operation. Further research will examine how these additives affect the anti-seizure and anti-wear properties of the lubricating oil used, which should give a broader view of the impact of these additives on the technical condition of the piston engine in operation. Full article

Glucocorticoid-induced bone loss is a severe and toxic effect of long-term therapy with glucocorticoids, which are currently prescribed for millions of people worldwide. Previous studies have uncovered that glucocorticoids reciprocally converted osteoblast lineage cells into endothelial-like cells to cause bone loss and showed that the modulations of Foxc2 and Osterix were the causative factors that drove this harmful transition of osteoblast lineage cells. Here, we find that the inhibition of aurora kinase A halts this transition and prevents glucocorticoid-induced bone loss. We find that aurora A interacts with the glucocorticoid receptor and show that this interaction is required for glucocorticoids to modulate Foxc2 and Osterix. Together, we identify a new potential approach to counteracting unwanted transitions of osteoblast lineage cells in glucocorticoid treatment and may provide a novel strategy for ameliorating glucocorticoid-induced bone loss. Full article

Cucurbita species are widely used as rootstocks for cucumber, watermelon, and other plants for the restriction of toxic Na⁺ transport from root to shoot. Previous studies have found distinct salt tolerance strategies between Cucurbita moschata and Cucurbita maxima; the former accumulates a large amount of Na⁺ in the root, while the latter accumulates Na⁺ in the shoot. To further study the mechanism of Na⁺ transport in plants, four reciprocal grafts were made between MB (C. moschata) and JHL (C. maxima), denoted as MB/MB, JHL/JHL, MB/JHL, and JHL/MB (scion/rootstock). The results showed that using MB as the rootstock effectively reduced the accumulation of Na⁺ in the scion. Conversely, JHL rootstock tended to transfer more Na⁺ to the scion. To clarify this phenomenon, the velocities of Na⁺ flows on the root surface, stem, and vein of grafting combinations were measured using non-invasive micro-test technology. Compared with the seedlings using JHL as rootstock, the grafted combination with MB as rootstock had a higher root Na⁺ efflux and lower Na⁺ fluxes in the stem and vein. qRT-PCR analyses revealed the critical roles of salt overly sensitive 1 and high-affinity potassium as components of the mechanism enabling Na⁺ exclusion from the root and Na⁺ unloading from the stem xylem. Compared with the seedlings using MB as rootstocks, the JHL-grafted plants showed more rapid stomatal closure and decreased transpiration rate in the first three hours after salt stress but maintained a higher level under prolonged salt treatment (120 h). The tissue tolerances of JHL and MB were assessed using the isolated leaves under NaCl to exclude the influence of the root and stem. The results showed that the salinity inflicted more serious damage to MB leaves than to JHL leaves. qRT-PCR analyses indicated that the intracellular Na⁺/H⁺ transporter in the leaf vein was involved in this process. All these findings indicated that C. moschata and C. maxima adopted different strategies for regulating Na⁺ transport, and grafting can be used as a tool to create more salt-tolerant plants. Full article

Glucocorticoid-induced bone loss is a toxic effect of long-term therapy with glucocorticoids resulting in a significant increase in the risk of fracture. Here, we find that glucocorticoids reciprocally convert osteoblast-lineage cells into endothelial-like cells. This is confirmed by lineage tracing showing the induction of endothelial markers in osteoblast-lineage cells following glucocorticoid treatment. Functional studies show that osteoblast-lineage cells isolated from glucocorticoid-treated mice lose their capacity for bone formation but simultaneously improve vascular repair. We find that the glucocorticoid receptor directly targets Foxc2 and Osterix, and the modulations of Foxc2 and Osterix drive the transition of osteoblast-lineage cells to endothelial-like cells. Together, the results suggest that glucocorticoids suppress osteogenic capacity and cause bone loss at least in part through previously unrecognized osteoblast–endothelial transitions. Full article

Evidence for a role for vitamin D in non-alcoholic fatty liver disease (NAFLD) pathogenesis is conflicting. As Mendelian randomisation (MR) avoids many limitations of conventional observational studies, this two-sample bidirectional MR analysis was conducted to determine the following: (i) whether genetically predicted 25-hydroxyvitamin D [25(OH)D] levels are a risk factor for NAFLD, and (ii) whether genetic risk for NAFLD influences 25(OH)D levels. Single-nucleotide polymorphisms (SNPs) associated with serum 25(OH)D levels were obtained from the European ancestry-derived SUNLIGHT consortium. SNPs associated with NAFLD or NASH (p-value < 1 × 10⁻⁵) were extracted from previous studies and supplemented by genome-wide association studies (GWASs) performed in the UK Biobank. These GWASs were done both without (primary analysis) and with (sensitivity analysis) the population-level exclusion of other liver diseases (e.g., alcoholic liver diseases, toxic liver diseases, viral hepatitis, etc.). Subsequently, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran’s Q statistic, MR-Egger regression intercept, MR pleiotropy residual sum and outlier (MR-PRESSO) analyses were used to assess pleiotropy. No causal association of genetically predicted serum 25(OH)D (per standard deviation increase) with risk of NAFLD was identified in either the primary analysis: n = 2757 cases, n = 460,161 controls, odds ratio (95% confidence interval): 0.95 (0.76, −1.18), p = 0.614; or the sensitivity analysis. Reciprocally, no causal association was identified between the genetic risk of NAFLD and serum 25(OH)D levels, OR = 1.00 (0.99, 1.02, p = 0.665). In conclusion, this MR analysis found no evidence of an association between serum 25(OH)D levels and NAFLD in a large European cohort. Full article

In recent years, the interest in renewable fuels has increased mainly due to regulations regulating the permissible limits of toxic components of exhaust gases emitted by reciprocating engines. This paper presents the results of a comparison of the effects of fueling a compression-ignition piston engine with a mixture of diesel fuel and n-butanol, as well as RME (Rapeseed Oil Methyl Esters) biodiesel and n-butanol. The tests were carried out for a constant load and a wide energetic share of fuels in the mixture. The main focus was on the assessment of combustion stability, the uniqueness of the combustion stages, and the assessment of the fuel type influence on the CA50 angle. The tests show that RME offers the possibility of efficient combustion with n-butanol with up to 80% energy share. The share of n-butanol has a positive effect on the engine’s efficiency and very effectively reduces soot emissions. Without the influence on COV_IMEP, the share of n-butanol up to 40% in the mixture with diesel fuel and up to 80% in the mixture with RME was recorded. Combustion of RME with n-butanol was more stable. The share of n-butanol in the mixture with diesel fuel caused an increase in NO_x emissions, and co-combustion with RME caused a decrease in emissions. Full article

Herein, the particle size distributions (PSDs) and shape analysis of in vivo bioproduced particles from aqueous Au³⁺ and Eu³⁺ solutions by the cyanobacterium Anabaena sp. are examined in detail at the nanoscale. Generally, biosynthesis is affected by numerous parameters. Therefore, it is challenging to find the key set points for generating tailored nanoparticles (NPs). PSDs and shape analysis of the Au and Eu-NPs were performed with ImageJ using high-resolution transmission electron microscopy (HR-TEM) images. As the HR-TEM image analysis reflects only a fraction of the detected NPs within the cells, additional PSDs of the complete cell were performed to determine the NP count and to evaluate the different accuracies. Furthermore, local PSDs were carried out at five randomly selected locations within a single cell to identify local hotspots or agglomerations. The PSDs show that particle size depends mainly on contact time, while the particle shape is hardly affected. The particles formed are distributed quite evenly within the cells. HR-PSDs for Au-NPs show an average equivalent circular diameter (ECD) of 8.4 nm (24 h) and 7.2 nm (51 h). In contrast, Eu-NPs preferably exhibit an average ECD of 10.6 nm (10 h) and 12.3 nm (244 h). Au-NPs are classified predominantly as “very round” with an average reciprocal aspect ratio (RAR) of ~0.9 and a Feret major axis ratio (FMR) of ~1.17. Eu-NPs mainly belong to the “rounded” class with a smaller RAR of ~0.6 and a FMR of ~1.3. These results show that an increase in contact time is not accompanied by an average particle growth for Au-NPs, but by a doubling of the particle number. Anabaena sp. is capable of biosorbing and bioreducing dissolved Au³⁺ and Eu³⁺ ions from aqueous solutions, generating nano-sized Au and Eu particles, respectively. Therefore, it is a low-cost, non-toxic and effective candidate for a rapid recovery of these sought-after metals via the bioproduction of NPs with defined sizes and shapes, providing a high potential for scale-up. Full article