Biological Effects Research Articles

Uptake of tire-derived compounds in leafy vegetables and implications for human dietary exposure

IntroductionTire and road wear particles are one of the most abundant types of microplastic entering the environment. The toxicity of tire and road wear particles has been linked to their organic additives and associated transformation products. Tire and road wear particles, and associated tire-derived compounds are introduced to the agricultural environment via atmospheric deposition, irrigation with reclaimed wastewater, and the use of biosolids (treated sewage sludge) as fertilizer. In the agricultural environment, these tire-derived compounds could be taken up by edible plants, leading to human exposure.MethodsSixteen tire-derived compounds were measured in twenty-eight commercial leafy vegetable samples from four countries. Based on the results, the estimated daily intake of these tire-derived compounds was calculated due to leafy vegetable consumption based on local diets under a mean and maximum concentration scenario.ResultsIn commercial leafy vegetables, six tire-derived compounds were detected: benzothiazole (maximum concentration—238 ng/g dry weight), 2-hydroxybenzothiazole (maximum concentration—665 ng/g dry weight), 1,3-diphenylguanidine (maximum concentration—2.1 ng/g dry weight), N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD, maximum concentration—0.4 ng/g dry weight), N-Isopropyl-N-phenyl-4-phenylenediamine (IPPD, maximum concentration—0.1 ng/g dry weight), and N-phenyl-N-cyclohexyl-p-phenylenediamine (CPPD, maximum concentration—0.3 ng/g dry weight). At least one compound was present in 71% of samples analyzed. The estimated daily intake for 1,3-diphenylguanidine ranged from 0.05 ng/person/day in the mean scenario to 4.0 ng/person/day in the maximum scenario; benzothiazole ranged from 12 to 1,296 ng/person/day; 6PPD ranged from 0.06 to 2.6 ng/person/day; IPPD ranged from 0.04 to 1.1 ng/person/day; CPPD ranged from 0.05 to 2.6 ng/person/day.DiscussionStatistical analyses did not reveal correlation between known growth conditions and tire-derived compound concentrations in the leafy vegetable samples. The estimated daily intake via leafy vegetable consumption was generally lower than or comparable to the estimated daily intake via other known sources. However, we show that tire-derived compounds are taken up by foodstuff, and exposure might be higher for other produce. Future studies are needed to uncover pathways of tire-derived compounds from road to food, assess the exposure to transformation products, and investigate the biological effects associated with this exposure.

Exposome on skeletal muscle system: a mini-review.

Exposomics is an ever-expanding field which captures the cumulative exposures to chemical, biological, physical, lifestyle, and social factors associated with biological responses. Since skeletal muscle is currently considered as the largest secretory organ and shows substantial plasticity over the life course, this reviews addresses the topic of exposome and skeletal muscle by reviewing the state-of-the-art evidence and the most intriguing perspectives. Muscle stem cells react to stressors via phosphorylated eukaryotic initiation factor 2α and tuberous sclerosis 1, and are sensible to hormetic factors via sirtuin 1. Microplastics can delay muscle regeneration via p38 mitogen-activated protein kinases and induce transdifferentiation to adipocytes via nuclear factor kappa B. Acrolein can inhibit myogenic differentiation and disrupt redox system. Heavy metals have been associated with reduced muscle strength in children. The deep study of pollutants and biological features can shed new light on neuromuscular pathophysiology. The analysis of a time-varying and dynamic exposome risk score from a panel of exposure and phenotypes of interest is promising. The systematization of hormetic factors and the role of the microbiota in modulating the effects of exposure on skeletal muscle responses are also promising. The comprehensive exposure assessment and its interactions with endogenous processes and the resulting biological effects deserve more efforts in the field of muscle health across the lifespan.

Harnessing the Power of Polyphenols: A New Frontier in Disease Prevention and Therapy.

There are a wide variety of phytochemicals collectively known as polyphenols. Their structural diversity results in a broad range of characteristics and biological effects. Polyphenols can be found in a variety of foods and drinks, including fruits, cereals, tea, and coffee. Studies both in vitro and in vivo, as well as clinical trials, have shown that they possess potent antioxidant activities, numerous therapeutic effects, and health advantages. Dietary polyphenols have demonstrated the potential to prevent many health problems, including obesity, atherosclerosis, high blood sugar, diabetes, hypertension, cancer, and neurological diseases. In this paper, the protective effects of polyphenols and the mechanisms behind them are investigated in detail, citing the most recent available literature. This review aims to provide a comprehensive overview of the current knowledge on the role of polyphenols in preventing and managing chronic diseases. The cited publications are derived from in vitro, in vivo, and human-based studies and clinical trials. A more complete understanding of these naturally occurring metabolites will pave the way for the development of novel polyphenol-rich diet and drug development programs. This, in turn, provides further evidence of their health benefits.

Increasing Risks to the Health of the Invertebrates-Balancing between Harm and Benefit.

The article discusses the issue of extensive use of detergents and sanitizers in the time of new challenges associated with the COVID-19 (SARS-CoV-2) pandemic. These agents could pose threats to the existence of free-living invertebrates as essential components of the ecosystem. The biological effects of the mentioned classes of substances, their metabolites, and combined effects in the mixture have not been studied enough. The main challenges in trying to balance the threats and benefits of using such substances are the lack of knowledge of the biological effects of these products, the gaps in testing invertebrates' responses, and changes in environment-related regulations to minimize risks to animals and humans. Numerous studies in this field still leave research gaps, particularly concerning the combined toxicity of well-known and widely used disinfectants, surfactants, and heavy metals, posing potential future challenges. Additionally, the review identified the need for additional testing of invertebrates for their sensitivity to disinfectants and surfactants of different compositions, including improved (non-invasive) methods, studies for early life stages, and comparative studies of species resilience.

Chemical and biological effects of zero-valent iron (ZVI) concentration on in-situ production of H2 from ZVI and bioconversion of CO2 into CH4 under anaerobic conditions

The conversion of carbon dioxide (CO2) to methane (CH4) is a strategy for sequestering CO2. Zero-valent iron (ZVI) has been proposed as an alternative electron donor for the CO2 reduction to CH4. In this study, the effects of ZVI concentrations on the abiotic production of H2 (without the action of microorganisms) in the first part and on the biological conversion of CO2 to CH4 using ZVI as a direct electron donor in the second part were examined. In the abiotic H2 production, the increase in the ZVI concentration from 16 to 32, 64, and 96 g/L was found to have positive effects on both the amounts of H2 generated and the rates of H2 production because the extent of ZVI oxidation positively correlates with increasing surface area. Nevertheless, the increase in ZVI concentration from 96 to 224 g/L did not benefit the H2 production because the ZVI dissolution was suppressed by the increasing aqueous pH above 10. In the bioconversion of CO2 to CH4 using ZVI as an electron donor, the main methanogenesis pathway occurred via hydrogenotrophic methanogenesis at pH 8.7–9.5 driven by the genus Methanobacterium of the class Methanobacteria. At ZVI concentrations of 64 g/L and above, the production of volatile fatty acid (VFA) became clear. Acetate was the main VFA, indicating the induction of homoacetogenesis at ZVI concentrations of 64 g/L and above. In addition, the presence of propionate as the second major VFA suggests the production of propionate from CO2 and acetate under conditions with high H2 partial pressure. The results indicated that the pathway for ZVI/CO2 conversion to CH4 was competitive between hydrogenotrophic methanogenesis and homoacetogenesis.

Features of generation and differentiation of iPSCs into retinal cells for modeling human hereditary diseases

Currently, numerous studies demonstrate the possibility of generating human iPSCs from somatic cells, which ensures the rapid progress of research in human diseases for which there are no relevant animal models or limited access to primary human tissues and cells. The utilization of technology for generation of iPSCs with their subsequent differentiation is, among other things, a promising approach for studying the disease pathogenesis and developing methods for treating optical neuropathies and retinopathy - the most common types of pathologies of the visual system, in which degeneration of retinal ganglion cells occurs (and, as a consequence, optic nerve atrophy) or pigment epithelial cells and photoreceptors are affected, respectively. This review presents a variety of protocols for generating iPSCs from somatic cells and their subsequent differentiation, with an emphasis on the observed biological effects of the resulting cell cultures, including organoids, and also discusses the prospects of using such models. The article may be useful to researchers studying the pathogenesis of various hereditary forms of blindness and developers of approaches for the treatment of these diseases who need to obtain a relevant cellular model.

Integrated meta-analyses of genome-wide effects of PM2.5 in human cells identifies widespread dysregulation of genes and pathways associated with cancer progression and patient survival

Epidemiological studies have consistently shown a positive association between exposure to ambient PM2.5, a major component of air pollution, and various types of cancer. Previous biological research has primarily focused on the association between PM2.5 and lung cancer, with limited investigation into other cancer types. In this study, we conducted a meta-analysis on multiple PM2.5-treated normal human cell lines to identify potential molecular targets and pathways of PM2.5. Our analysis revealed 310 common differentially expressed genes (DEGs) that exhibited significant dysregulation upon exposure to PM2.5. These dysregulated genes covered a diverse range of functional categories, including oncogenes, tumor suppressor genes, and immune-related genes, which collectively contribute to PM2.5-induced carcinogenesis. Pathway enrichment analysis revealed the up-regulation of pathways associated with HIF-1, VEGF, and MAPK signalling, all of which have been implicated in various cancers. Induction in the levels of HIF pathway genes (HIF1⍺, HIF2⍺, VEGFA, BNIP3, EPO and PGK1) upon PM2.5 treatment was also confirmed by qRT-PCR. Furthermore, the construction of a protein-protein interaction (PPI) network unveiled hub genes, such as NQO1 and PDGFRB, that are known to be dysregulated and significantly correlated with overall survival in lung and breast cancer patients, suggesting their potential clinical significance. This study provides a deep insight into how PM2.5-mediated dysregulation of oncogenes or tumor suppressor genes across various human tissues may play an important role in PM2.5-induced carcinogenesis. Further exploration of these dysregulated molecular targets may enhance our understanding of the biological effects of PM2.5 and facilitate the development of preventive strategies and targeted therapies for PM2.5-associated cancers.

Exosomes derived from adipose tissue-derived stem cells alleviated H2O2-induced oxidative stress and endothelial-to-mesenchymal transition in human umbilical vein endothelial cells by inhibition of the mir-486-3p/Sirt6/Smad signaling pathway

Hypertrophic scar (HS) is characterized by excessive collagen deposition and myofibroblasts activation. Endothelial-to-mesenchymal transition (EndoMT) and oxidative stress were pivotal in skin fibrosis process. Exosomes derived from adipose tissue-derived stem cells (ADSC-Exo) have the potential to attenuate EndoMT and inhibit fibrosis. The study revealed reactive oxygen species (ROS) levels were increased during EndoMT occurrence of dermal vasculature of HS. The morphology of endothelial cells exposure to H2O2, serving as an in vitro model of oxidative stress damage, transitioned from a cobblestone-like appearance to a spindle-like shape. Additionally, the levels of endothelial markers decreased in H2O2-treated endothelial cell, while the expression of fibrotic markers increased. Furthermore, H2O2 facilitated the accumulation of ROS, inhibited cell proliferation, retarded its migration and suppressed tube formation in endothelial cell. However, ADSC-Exo counteracted the biological effects induced by H2O2. Subsequently, miRNAs sequencing analysis revealed the significance of mir-486-3p in endothelial cell exposed to H2O2 and ADSC-Exo. Mir-486-3p overexpression enhanced the acceleration of EndoMT, its inhibitors represented the attenuation of EndoMT. Meanwhile, the target regulatory relationship was observed between mir-486-3p and Sirt6, whereby Sirt6 exerted its anti-EndoMT effect through Smad2/3 signaling pathway. Besides, our research had successfully demonstrated the impact of ADSC-Exo and mir-486-3p on animal models. These findings of our study collectively elucidated that ADSC-Exo effectively alleviated H2O2-induced ROS and EndoMT by inhibiting the mir-486-3p/Sirt6/Smad axis.Graphical A schematic diagram summarizing the impact of ADSC-Exo on oxidative stress and endothelial-to-mesenchymal transition in endothelial cells was presented in this study. ADSC-Exo effectively alleviated the accumulation of ROS in endothelial cells induced by H2O2 and suppressed the pro-fibrotic function through modulation of the mir-486-3p/Sirt6/Smad signaling pathway. ADSC-Exo attenuated the up-regulation of mir-486-3p in endothelial cells exposure to H2O2, establishing a target relationship between mir-486-3p and Sirt6. Overexpression of Sirt6 inhibited the occurrence of endothelial-to-mesenchymal transition, thereby suppressing collagen deposition and myofibroblasts activity by the regulation of Smad2/3 phosphorylation. Consequently, this led to a reduction in hypertrophic scar formation.Graphical Highlights1. The occurrence and development of ROS and endothelial-to-mesenchymal transition promoted hypertrophic scar fibrosis;2. H2O2 induced oxidative stress and EndoMT of endothelial cells, whereas ADSC-Exo ameliorated the process;3. Mir-486-3p was crucial for H2O2-induced EndoMT and the improvement of ADSC-Exo;4. Mir-486-3p directly targeted Sirt6 to facilitate EndoMT by regulating Smad signaling pathway.

Synthesis and characterization of indazole derived Schiff base ligands and their metal complexes: Biological and computational studies

Indazoles represent one of the most important heterocycles in drug molecules. Therefore, in the pursuit of potent biological agents, a series of ligands (HL1-HL4) and their corresponding transition metal complexes [M(L1-L4)2(H2O)2] were synthesized by the condensation reaction of 6-aminoindazole with various derivatives of salicylaldehyde. Further, the compounds underwent characterization through several physicochemical (TGA, powder XRD, SEM, EDAX) and spectroscopic techniques (FT-IR, UV–Vis, NMR, mass spectrometry, ESR). These techniques suggested hexacoordinated stereochemistry of the metal complexes, where ligands chelate via oxygen atom of phenolic ring, azomethine nitrogen and oxygen atom of water molecules in 1:2 (M:L) molar ratio. The thermal stability of the complexes was demonstrated by thermal analysis revealing three step decompositions leaving behind metal oxide as an end residue. The surface morphology of the ligands was distinct from metal complexes as revealed by SEM analysis, while mapping images demonstrated the simultaneously existence of the elements. While, to ascertain the nature of the obtained compounds (crystalline or amorphous), powder X-ray investigation was conducted by utilizing a wavelength of 1.54 Å. The compound’s antioxidant potential was assessed through DPPH assays and anti-inflammatory activity was evaluated using BSA denaturation inhibition assay, while their antimicrobial potential was evaluated against six microbial strains (E. coli, S. aureus, P. aeruginosa, B. subtilis, C. albicans, A. niger) by serial dilution approach. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. HL2 (2) and its Cu(II), Zn(II) complexes (11, 12) exhibited potent antimicrobial activity (MIC value: 0.0047, 0.0048 µmol/mL against B. subtilis) and potent anti-inflammatory efficacy (IC50 value: 6.7 ± 0.044, 6.9 ± 0.036 µM). All the complexes exhibited potent antioxidant activity and their is enhancement in the activity of Schiff base ligands upon complexation, complex (19) demonstrated the greatest activity with IC50 value 2.1 ± 0.059. Additionally, the ADMET score provided a robust indication of the compounds’ drug-like behaviour. Furthermore, the biological effectiveness of the highly microbial potent ligand HL2 (2) and its complexes (9–12) was demonstrated through computational studies. The binding studies exposed that complexes (11, 12) exhibited lowest binding energy at −7.8, −7.9 kcal/mol. While, DFT study emphasized that complex (12) exhibits the highest electrophilicity index value (6.359), suggesting its affinity for binding with biological molecules and also revealed that complexes exhibit greater potency compared to the ligands and could potentially be utilized as drugs for combatting pathogen-induced malformations.

Investigating the biochemical response of proton minibeam radiation therapy by means of synchrotron-based infrared microspectroscopy

The biology underlying proton minibeam radiation therapy (pMBRT) is not fully understood. Here we aim to elucidate the biological effects of pMBRT using Fourier Transform Infrared Microspectroscopy (FTIRM). In vitro (CTX-TNA2 astrocytes and F98 glioma rat cell lines) and in vivo (healthy and F98-bearing Fischer rats) irradiations were conducted, with conventional proton radiotherapy and pMBRT. FTIRM measurements were performed at ALBA Synchrotron, and multivariate data analysis methods were employed to assess spectral differences between irradiation configurations and doses. For astrocytes, the spectral regions related to proteins and nucleic acids were highly affected by conventional irradiations and the high-dose regions of pMBRT, suggesting important modifications on these biomolecules. For glioma, pMBRT had a great effect on the nucleic acids and carbohydrates. In animals, conventional radiotherapy had a remarkable impact on the proteins and nucleic acids of healthy rats; analysis of tumour regions in glioma-bearing rats suggested major nucleic acid modifications due to pMBRT.

Exploration of Rhenium Bisquinoline Tricarbonyl Complexes for their Antibacterial Properties.

Metal complexes have emerged as a promising source for novel classes of antibacterial agents to combat the rise of antimicrobial resistance around the world. In the exploration of the transition metal chemical space for novel metalloantibiotics, the rhenium tricarbonyl moiety has been identified as a promising scaffold. Here we have prepared eight novel rhenium bisquinoline tricarbonyl complexes and explored their antibacterial properties. Significant activity against both Gram-positive and Gram-negative bacteria was observed. However, all complexes also showed significant toxicity against human cells, putting into question the prospects of this specific rhenium compound class as metalloantibiotics. To better understand their biological effects, we conduct the first mode of action studies on rhenium bisquinoline complexes and show that they are able to form pores through bacterial membranes. Their straight-forward synthesis and tuneability suggests that further optimisation of this compound class could lead to compounds with enhanced bacterial specificity.

Studies on Morphological Effect of Some Pesticides on Fresh Water Fish, Labeo rohita in Sai River of Jaunpur District, Uttar Pradesh, India

Pesticides are one of the potentially harmful toxic chemicals introduced into the aquatic environment. Fish serve as important bio-indicators for aquatic life. Widely used pesticides formulation two investigate possible chemical biological and toxicological effects of pesticides that may enter into our eco-system. Effects of pesticides (herbicides insecticides, rodenticides and fungicides) to loss protein content of the liver gill and intestinal tissue of the fresh water fish, Labeorohita.The Recent study is aimed two assess the toxicological impacts of treated and untreated effluents on aquatic fresh water fish, Labeo rohita. The Most common edible fish having diverse characters includes difference in morphology, food and feeding etc. Symptoms were nearly identical on various host spp (Labeo rohita. with respect to behaviour of the infected fish. The toxicity of pesticides to an organism is usualy expressed in terms of the LD50 (lethal dose 50 percent) and LC50 (50 percent lethal concentration) observed the behavioural studies of exposed to Labeorohita. Therefore, the protection and prevention of aquatic ecosystem will be possible only with the appropriate and rationalized application of pesticides.

Antibacterial nanofibrous film encapsulated with 4-terpineol/β-cyclodextrin inclusion complexes: Relative humidity-triggered release and shrimps preservation application

Antibacterial active packaging enables extensive biological effects to improve food safety. However, it still remains difficult to achieve controlled and precise release of bioactive compounds to the specific target location with required quantity in food packaging applications. Here, a novel relative humidity (RH) - responsive polyvinyl alcohol/chitosan (PVA/CS) composite nanofibrous film incorporated with 4-terpineol/β-cyclodextrin inclusion complexes (4-TA@β-CD ICs) was engineered by electrospinning that can be exploited as a functional packaging materials. The characterization results showed the thermal stability of the films was enhanced after the incorporation due to the hydrogen bonds between ICs and biopolymers. Besides, the 4 wt% 4-TA@β-CD ICs/PVA/CS film exhibited optimized morphology, crystallinity, mechanical properties, and water vapor permeability. The incorporation of ICs dramatically promoted the antioxidant and inhibition activity of the film especially towards Shewanella putrefaciens. Moreover, the release behavior of 4-TA indicated that high RH accelerated the releasing rate, and the film obtained a sustained-release effect. Finally, the film with long-term antibacterial effectiveness succeeded in extending the shelf life of Litopenaeus vannamei shrimps by an additional 2 days at 4 °C. This work developed a RH-responsive release packaging material, which may serve as an effective active food packaging.

Helium Ion Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications.

#2000 Analysis between site-specific N-glycosylation of monoclonal immunoglobulin and complement system activation

Abstract Background and Aims Monoclonal immunoglobulin produced by clonal plasma cells is the main cause in multiple myeloma (MM) and monoclonal gammopathy of renal significance (MGRS). Hypocomplementemia and deposition of complement components in the kidney is observed in some patients with MM or MGRS. Previous studies have suggested that glycosylation of the immunoglobulin was associated with complement-mediated-effector activities. Whereas, site-specific N-glycosylation characterization for monoclonal immunoglobulin in MM or MGRS and its effects on complement system activation still remains unclear. Method We separated plasma monoclonal IgG1 and IgA immunoglobulin from patients with MM and human plasma immunoglobulin from healthy controls (HC). Purified IgG and IgA molecules were digested by trypsin. Tryptic peptides without enrichment of intact N-glycopeptides were analyzed using a combination of electron-transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) mass spectrometry (EThcD-sceHCD-MS/MS). N-glycosylation characterization was compared between monoclonal immunoglobulin from MM patients and healthy controls and its association with complement level was evaluated. Results A total of 46 IgG1 digestion samples (HC, n = 16; MM, n = 30) and 38 IgA1 digestion samples (HC, n = 16; MM, n = 22) were analyzed using the EThcDsceHCD-MS/MS. On average, 34 and 37 unique N-glycopeptides of IgG1, 19 unique N-glycans per IgG were identified from HC and MM. The relative abundance of fucosylated N-glycans of IgG1 in MM was significantly higher than HC (94.7% vs 88.8%, p = 0.002). Other types of N-glycans including sialylated, hybrid and complex were similar between the two groups. The types of N-glycans including fucosylated, sialylated, hybrid and complex were similar between patients with hypocomplementemia and normal complement levels. Regarding IgA1, on average, 63 and 52 unique N-glycopeptides of IgA1, 40 and 35 unique N-glycans per IgA were identified from HC and MM. The relative abundance of fucosylated (41.0% vs 26.4%, p < 0.001), sialylated (61.0% vs 45.6%, p = 0.003), mannose (2.44% vs 0.28%, p < 0.001) N-glycans of IgA1 in MM was significantly higher than HC. In MM, the relative abundance of mannose N-glycans of IgA1 in patients with hypocomplementemia was significantly lower than patients with normal complement levels (1.69% vs 7.52%, p < 0.001). The relative abundance of fucosylated and sialylated N-glycans were similar between patients with hypocomplementemia and normal complement levels. Conclusion Site-specific N-glycosylation characterization of monoclonal IgG1 and IgA1 in MM patients were differentially expressed from healthy controls. Certain specific N-glycan types were associated with complement levels. These findings laid a foundation for future investigations of their biological effects.

L-2-Aminopimelic acid acts as an auxin mimic to induce lateral root formation across diverse plant species.

The identification of chemicals that modulate plant development and adaptive responses to stresses has attracted increasing attention for agricultural applications. Recent basic studies have identified functional amino acids that are essential for plant organogenesis, indicating that amino acids can regulate plant growth. In this study, we newly identified 2-aminopimelic acid (2APA), a nonproteinogenic amino acid, as a novel bioactive compound involved in root morphogenesis. This biological effect was confirmed in several plant species. Our phenotypic analysis revealed that the bioactive 2APA is an l-form stereoisomer. Overall, our study identified a promising root growth regulator and provided insight into the intricate metabolism related to root morphology.

Enhancing the biological functionality of poly (lactic‐co‐glycolic acid) cage‐like structures through surface modification with micro‐ and nano‐sized hydroxyapatite particles

AbstractBiomaterials with exceptional performance are crucial for addressing the challenges of complex bone regeneration. Compared with traditional three‐dimensional scaffolds, injectable microspheres enable new strategies for the treatment of irregular bone defects. Biodegradable poly (lactic‐co‐glycolic acid) has found widespread applications as microcarriers of drugs, proteins, and other active macromolecules. Applied to the surface of poly (lactic‐co‐glycolic acid) cage‐like structures (PLGA‐CAS), hydroxyapatite (HA) effectively reduces inflammation while enhancing biological effects. In this study, we loaded the surface of PLGA‐CAS with micro‐ and nano‐hydroxyapatite particles, referred to as μHA/PLGA‐CAS and nHA/PLGA‐CAS, respectively. Subsequently, their material characteristics and biological effects were assessed. The incorporation of hydroxyapatite onto PLGA‐CAS resulted in enhanced surface roughness and hydrophilicity, coupled with improved thermal stability and delayed degradation. Furthermore, μHA/PLGA‐CAS induced osteogenic differentiation of osteoblast precursor cells, while nHA/PLGA‐CAS improved endothelial cell adhesion and stimulated angiogenic differentiation in vitro. Collectively, these findings suggest that μHA/PLGA‐CAS and nHA/PLGA‐CAS, each with distinct characteristics, hold significant potential for application as microcarriers in various biomedical contexts.

#2084 Biologic effect evaluation of de novo long-term release tacrolimus on metabolizer phenotype and T cell composition after kidney transplantation

Abstract Background and Aims Kidney transplantation (KTX) is the current treatment of choice in patients with kidney failure. Since immunosuppressive medication to prevent acute rejection is still needed in high doses with frequent adverse events, new strategies to achieve risk-appropriate personalization of immunosuppression are needed. Calcineurin inhibitors are the cornerstone of T cell suppression, currently available in different release formulations including once daily long-term release tacrolimus (LCPT) and regular twice daily immediate release tacrolimus (IRT). Little is known about the temporal evolution of tacrolimus metabolism potentially influencing T cell composition and clinical endpoints between different tacrolimus formulations after KTX. Method To evaluate the influence of de novo LCPT on clinical endpoints, metabolizer phenotype and immune cell composition after KTX, subgroup analysis of a single-center, prospective, observational cohort study including 32 patients started on LCPT (0.1 mg/kg) and 55 patients started on IRT (0.1 mg/kg) was conducted. Peripheral blood mononuclear cells were isolated from whole blood samples drawn before KTX, 2 months and 12 months after KTX for flow cytometry analysis. Study visits were simultaneously conducted to obtain tacrolimus dosing, plasma levels, acute rejection and infection incidence. Statistical analysis was done using GraphPad Prism (v10), accepting significance for p < 0.05, and flow cytometry analysis was done using FlowJo (v10) software. Results The cohort represented KTX recipients with a median age of 60 years and similar distributions of gender, HLA-mismatches and induction therapy. Clinical outcome data showed a trend towards lower acute rejection rate, lower serum-creatinine values and increased incidence of BK-viremia in LCPT treated patients. Rejection rate was associated with a fast-metabolizer phenotype (HR 3.9; 1.1-6.8, p < 0.01) and HLA mismatch > 3 (HR 4.0; 1.2-7.3, p < 0.01) while this effect was blunted in the LCPT group (HR 1.9; 0.7-3.2, p = 0.67 and HR 0.9; 0.3-1.4, p = 0.38 respectively) in a multivariate Cox-regression model. Cluster exploration and tSNE analysis of flow cytometry data revealed diminution of activated-proliferative effector and regulatory T cell trajectories, with significant reduction in cell counts of CD4+CD15s+/CD45RA-Ki67+Foxp3+ Treg and in CD4+CD147high/CD45RA-LAP+HLADR+FcRL3+ effector T cells in LCPT treated patients after KTX. Conclusion Induction with de novo LCPT was associated with a blunted influence of metabolizer phenotype and HLA-mismatch on acute rejection in our cohort. Major changes were detected in peripheral T cell composition after transplantation, with signs of a stronger immunosuppressive effect of LCPT on circulating activated T cells. Therefore, LCPT may be considered for KTX recipients with higher HLA-mismatch (i.e. “old-for-old”) or fast-metabolizer phenotype. Inclusion of changes in T cell composition as biologic effect measures may be worthwhile in future studies evaluating biomarkers to guide immunosuppression and predict complications after KTX.

Characterisation and comparison site-specific N-glycosylation of whey proteins from donkey and human colostrum and mature milk using glycoproteomics

Although the composition of donkey milk is similar to that of human milk, systematic comparisons of the site-specific N-glycosylation patterns of their whey proteins are lacking. In this study, hydrophilic interaction chromatography-based enrichment of intact N-glycopeptides, coupled with a site-specific glycoproteomics strategy, was used to systematically characterise whey N-glycoproteins in donkey colostrum (DC), donkey mature milk (DM), human colostrum (HC), and human mature milk (HM) for the first time. We identified 628, 347, 868, and 425 site-specific N-glycans mapped to 135, 67, 113, and 60 glycoproteins in DC, DM, HC, and HM, respectively. Bioinformatic analysis revealed the potential biological effects of N-glycosylation modifications on the whey proteins themselves. Our findings elucidated the composition of donkey and human milk whey N-glycoproteins and their potential structure-activity relationships and provided guidance for the production of specific functional donkey milk products and the development of donkey milk-based infant formulas.

Peripartal changes of metabolic and hormonal parameters in Romanian spotted cows and their relation with retained fetal membranes

This clinical study investigates various metabolic and physiological parameters in dairy cows during puerperium. Retained fetal membranes (RFM) is a significant postpartum complication that can affect the overall health, fertility and productivity of dairy cattle. The research focuses on changes in total proteins, albumin, glucose, triglycerides, total cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cortisol, insulin, and insulin-like growth factor 1 (IGF-1) levels among cows experiencing normal post-partum period (NP) and those with RFM. A significant increase in protein levels was noted during the post-partum period in the RFM group, indicating physiological impacts of RFM at this stage. Albumin levels showed significant differences, highlighting a significant biological effect of RFM in the post-partum period. Glucose levels varied significantly in the weeks leading to parturition, suggesting altered metabolic states in cows that suffered RFM. Triglyceride and cholesterol levels were significantly higher during the antepartum period in the group that experienced reproductive failure, indicating substantial alterations in lipid metabolism which could herald the apparition of RFM. AST and ALT levels provided insights into cellular stress and liver function, with significant increases noted around parturition which could be attributed to the substantial physiological strain of parturition itself. Cortisol levels were higher in RFM cows 2 weeks before parturition, which could indicate an increasing stress response or a physiological preparation for the upcoming labor, and may be more pronounced in cows predisposed to RFM. Insulin levels decreased significantly before and at parturition in RFM cows, indicating a strong energy deficit. IGF-1 levels decreased significantly in RFM cows after parturition. Significant changes in metabolic parameters, such as glucose, triglycerides, and cholesterol levels, delineate the pronounced metabolic challenges faced by cows with RFM. The study elucidates that while some variations are noted as parturition approaches, the most substantial impacts attributable to RFM on metabolic and physiological parameters occur after parturition. These changes may have implications for the health, recovery, and productivity of cows postpartum, suggesting the need for targeted management strategies to mitigate the effects of RFM.