High Concentrations Research Articles

Targeting CCR3 with antagonist SB 328437 sensitizes 5‑fluorouracil‑resistant gastric cancer cells: Experimental evidence and computational insights.

Gastric cancer (GC) ranks fifth globally in cancer diagnoses and third for cancer-related deaths. Chemotherapy with 5-fluorouracil (5-FU), a primary treatment, faces challenges due to the development of chemoresistance. Tumor microenvironment factors, including C-C motif chemokine receptor 3 (CCR3), can contribute to chemoresistance. The present study evaluated the effect of CCR3 receptor inhibition using the antagonist SB 328437 and the molecular dynamics of this interaction on resistance to 5-FU in gastric cancer cells. The 5-FU-resistant AGS cell line (AGS R-5FU) demonstrated notable tolerance to higher concentrations of 5-FU, with a 2.6-fold increase compared with the parental AGS cell line. Furthermore, the mRNA expression levels of thymidylate synthase (TS), a molecular marker for 5-FU resistance, were significantly elevated in AGS R-5FU cells. CCR3 was shown to be expressed at significantly higher levels in these resistant cells. Combining SB 328437 with 5-FU resulted in a significant decrease in cell viability, particularly at higher concentrations of 5-FU. Furthermore, when SB 328437 was combined with 5-FU at a high concentration, the relative mRNA expression levels of CCR3 and TS decreased significantly. Computational analysis of CCR3 demonstrated dynamic conformational changes, especially in extracellular loop 2 region, which indicated potential alterations in ligand recognition. Docking simulations demonstrated that SB 328437 bound to the allosteric site of CCR3, inducing a conformational change in ECL2 and hindering ligand recognition. The present study provides comprehensive information on the molecular and structural aspects of 5-FU resistance and CCR3 modulation, highlighting the potential for therapeutic application of SB 328437 in GC treatment.

Pharmacokinetics of Anti-Rheumatic drugs Methotrexate and Tofacitinib with its metabolite M9 in Rats by UPLC-MS/MS.

Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The clinical efficacy and safety of an administered tofacitinib, either monotherapy or in combination with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate (MTX), have been evaluated. The high plasma concentration with delayed medicine clearance may affect the liver and/or kidney functions. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC- MS/MS) method for the quantitative analysis of methotrexate, tofacitinib, and metabolite M9 in plasma of Sprague Dawley (SD) rats was developed, and its effectiveness was validated as well. Methotrexate, tofacitinib, M9 and fedratinib (internal standard, IS) were separated by gradient elution. The chromatography was performed on an Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column with the mobile phases of acetonitrile and 0.1% formic acid aqueous solution with different proportions at the flow rate of 0.30 mL/min. In the positive ionization mode, the analyzes were detected using a Xevo TQ-S triple quadrupole tandem mass spectrometer, with the following mass transition pairs: m/z 313.12 → 148.97 for tofacitinib, m/z 329.10 → 165.00 for M9 and m/z 455.12 → 308.05 for methotrexate. The obtained results manifested good calibration linearity over the ranges of tofacitinib at 0.1-100 ng/mL, M9 at 0.05-100 ng/mL, and methotrexate at 0.05-100 ng/mL. The lower limit of quantifications (LLOQs) of methotrexate, tofacitinib and M9 were 0.05 ng/mL, 0.1 ng/mL and 0.05 ng/mL, respectively. Intra-day and inter-day accuracy values were confirmed with a range of -6.3% to 12.7%, while intra-day and inter-- day precision values were ≤14.4%. Additionally, recoveries were greater than 86.5% for each compound without significant matrix effects. The currently established analytical method exhibited great potential for the evaluation of plasma concentrations of methotrexate, tofacitinib and M9 simultaneously, greatly reducing the detection time, which would serve as a supplementary role in formulating dose decisions to achieve personalized treatment, identify drugs that cause adverse reactions and finally, to assess drug-drug interactions on clinical studies.

Nanomaterials as a Potential Target for Infectious Parasitic Agents.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.

Environmental and occupational exposure to bisphenol compounds in Finland

The aim of the study was to assess non-occupational and occupational exposure to bisphenol compounds in Finland. The participants were 151 non-occupationally exposed volunteers and 15 potentially exposed employees of a sewage-pipe relining company and a floor-coating company. The following chemicals were measured in the urine samples: bisphenol A (BPA), bisphenol F (BPF), bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), and the metabolites of the latter two [bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H2O), bisphenol A bis(2,3-dihydroxypropyl) ether (BADGE·2H2O), bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether (BADGE·HCl·H2O), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl), and bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE·2HCl) and bisphenol F bis(2,3-dihydroxypropyl) ether (BFDGE·2H2O), and bisphenol F bis(3-chloro-2-hydroxypropyl) ether (BFDGE·2HCl)]. BADGE and BFDGE were also measured in breathing zone air samples and hand-wipe samples of the sewage-pipe relining and floor-coating workers.Non-occupational exposure to BPA has decreased in Finland. The BPF level of the non-occupationally exposed was higher than the respective levels reported in the recent literature. BPA and BPF concentrations in the workers' urine samples were in the same range as those in the corresponding concentrations of the non-occupationally exposed population. Higher concentrations of BADGE and BFDGE metabolites were found in some of the workers' urine samples. Elevated urine concentrations were also observed in the samples collected the next morning. Some of the urinary BADGE and BFDGE metabolite results correlated with the hand-wipe results.The results show that occupational exposure to BADGE and BFDGE may occur in sewage-pipe relining and floor-coating work. They also indicate that dermal contamination plays a role in total exposure. Although the measured urinary levels indicate that the absorption of these bisphenol compounds are unlikely to pose a systemic health risk, the risk of dermal sensitization remains.

Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders - a Mendelian randomization study

Mental disorders seriously affect people's health and social stability. This Mendelian randomization (MR) study was designed to investigate the causal relationship between circulating vitamin C (VC) or 25-hydroxyvitamin D (25(OH)D) levels and mental disorders. The data used for the MR analysis were derived from the summary genome-wide association studies (GWAS) database for VC and 25(OH)D and from the FinnGen consortium for fourteen mental disorders. Based on the inverse variance weighted (IVW) method, we found a potential causal association between circulating VC and anxiety disorders (IVW: OR=1.139, 95 %CI: 1.0231.269, P = 0.018). However, no causal association was found between VC or 25(OH)D and other mental disorders (P > 0.05). In the reverse MR analysis, individuals with Alzheimer's disease was causally associated with higher concentrations of circulating VC(P = 0.012), while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D (P = 0.012). However, the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders. In addition, there was no causal association between circulating VC and 25(OH)D (P > 0.05). Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

Cytotoxic effect of 1% and 3% Sodium hypochlorite as irrigation agent in primary teeth on human red blood cells: an in vitro study

Background and objectives. The endodontic treatment of primary teeth presents significant challenges due to their unique anatomical characteristics. To ensure a successful treatment, it is essential to evaluate a few factors. These factors include accurate diagnosis, disinfection protocol, intracanal medicaments, and irrigation solutions. While Sodium hypochlorite (NaOCl) has gained success as an irrigation agent in primary teeth, it is important to note that higher concentrations of NaOCl can potentially cause toxicity to the periapical environment if they pass through the tooth's apical foramina. Thus, this study compared the cytotoxicity of two different concentrations of sodium hypochlorite at varied volumes on red blood cells (RBC). Materials and methods. In order to evaluate the cytotoxicity potential, fresh human blood was collected from a single healthy individual and subjected to testing. For the test, 10 µL, 20 µL, 30 µL, 40 µL and 50 µL of 1% and 3% NaOCl were added to the RBC. The tubes were gently mixed and incubated at 37°C for 30 minutes. A UV-visible spectrophotometer was used to calculate the absorbance of the supernatant at a wavelength of 540 nm. Results. There was no significant difference in 1% sodium hypochlorite at different volumes with a p value >0.05 using Tukey's post hoc test. However, there was a significant difference between the volumes of 3% sodium hypochlorite at 40 and 50 µg/ml with a p value of 0.004 and 0.001 respectively. Conclusions. According to the current study's findings, 1% sodium hypochlorite solution exhibited less toxicity than 3% sodium hypochlorite.

Effect of foreign impurity and growth temperatures on hexagonal structure and fundamental properties of ZnO nanorods.

This study examined the influence of growth temperature and dopant concentration on the properties of Gd- and Ni-doped zinc oxide nanorods (ZnO NRs). ZnO seed layers were deposited on glass substrates using a sol-gel and dip-coating approach. Gd- and Ni-doped ZnO NRs were hydrothermally grown on the seed layers at different temperatures such as 75, 90, and 105°C for a constant growth time of 5 h. The crystal structure, optical, surface morphology views, and electrical properties of the NRs were extensively investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), UV-visible spectroscopy, and four probe experimental methods. The XRD analysis confirmed the successful substitution of Zn2+ ions by Gd3+ and Ni2+ within the ZnO main matrices. The reordering of hexagonal structures with varied electronegativity, ionic radius dimensions, and valence electron states of Gd and Ni dopants affected seriously the fundamental characteristic features of NRs. The SEM images showed that the ZnO NRs grown at 90°C possessed a more favorable surface morphology and well-defined hexagonal shape compared with those grown at other growth temperatures. Higher dopant concentration led to an increase in NR diameter but a decrease in density depending on the increase in the space between the NRs. Additionally, the optical transmittance was found to generally enhance with increasing dopant concentration. The results obtained highlighted the interplay between growth temperature, dopant type and concentration in tailoring the structural, morphological, and optical properties of Gd- and Ni-doped ZnO NRs, paving the way for the development of optimized nanomaterials for various applications. RESEARCH HIGHLIGHTS: The XRD analysis confirmed the successful substitution of Zn2+ ions by Gd3+ and Ni2+ within the ZnO main matrices. The SEM images showed that the ZnO NRs grown at 90°C possessed a more favorable surface morphology and well-defined hexagonal shape compared with those grown at other growth temperatures. The optical transmittance was found to generally enhance with increasing dopant concentration. The results obtained highlighted the interplay between growth temperature, dopant type and concentration in tailoring the structural, morphological, and optical properties of Gd- and Ni-doped ZnO NRs, paving the way for the development of optimized nanomaterials for various applications.

Mercury Levels in Selected Medicines and Dietary Supplements in Poland.

Current trends are promoting youth, beauty, health, and fitness. Individuals often seek out remedies, such as medicines or dietary supplements (DS), to achieve these goals. However, highly processed foods, chronic stress, and environmental pollution contribute to the development of civilization diseases. The aim of this study was to evaluate the mercury (Hg) content in medicines and DS that are available in Poland. A total of 139 preparations were tested (75 drugs, 64 DS). The medicines contained preparations belonging to antibacterial, antiviral, antifungal; analgesic, antipyretic, and anti-inflammatory; heart and blood vessel disease preventatives; respiratory tract infections treatment; diuretics; aiding digestion; supplements; antidiarrhoeals; anti-allergics; anti-rheumatics; antibiotics; and others. The tested dietary supplements had an effect on the following: improve the condition of skin, hair, and nails; vitamins; minerals; probiotics; weight loss; special for women; and others. The Hg content of the samples was determined using atomic absorption spectrometry (AAS). The Hg content of all the preparations varied widely (0.1-57.4µg/kg), with a median Hg concentration of 1.2µg/kg. The median Hg concentration for medicines was 0.8µg/kg, prescription medicines having higher Hg concentrations (0.9µg/kg) than over-the-counter (OTC) drugs (0.5µg/kg). For DS, the Hg content was found to be higher than for drugs, at 2.0µg/kg. The herbal preparations showed the highest Hg content among the individual DS groups (3.4µg/kg). The Hg concentrations in the tested drug and DS samples did not exceed acceptable standards. However, if multiple pharmaceutical preparations are taken simultaneously over a long period of time, and there is existing environmental exposure, there is a possibility of Hg concentration accumulation and adverse health effects.

Higher Plasma Myo-Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial

We previously reported that a combined myo-inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo-inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo-inositol in early pregnancy was associated with a PBL reduction [βadj −1.26 (95%CI −2.23, −0.29) mL per µmol/L myo-inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week-myo-inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo-inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved.

Relationships between pesticides, polychlorinated biphenyls, blood parameters and oxidative stress of white stork Ciconia ciconia chicks in Poland.

The white stork Ciconia ciconia is a bird species located at the top of the trophic pyramid in grassland and wetland ecosystems. This charismatic species is susceptible to pesticides and their environmental residues. In 2016, we collected blood samples from 114 white stork chicks across Western and Southern Poland. Chicks were sexed by molecular analysis and aged by development pattern. We studied the relationship between the concentration of pesticides (beta-HCH, heptachlor, aldrin, endrin, 4.4'-DDD, 4.4'-DDE and 4.4'-DDT) and of PCB in the chicks' blood with blood morphology and biochemistry parameters in the blood. The mean (± SD) values of concentrations of above detection level pesticides were: for (1) beta-HCH 4.139 ± 19.205; (2) 4.4'-DDE 9.254 ± 91.491 and additionally (3) PCB 16.135 ± 44.777ppb. We found negative relationships between beta-HCH and oxidative stress enzyme activity in the blood, between beta-HCH and leukocyte concentration and between 4.4'-DDE and catalase activity. We also found a positive relationship between the concentration of pesticides in blood and the age of chicks. Interestingly, we found a higher concentration of PCB in the blood of male stork chicks than in female stork chicks. We provide more evidence that the presence of pesticides in the environment can be a strong stress factor, shaping the health status of birds.

Toxicokinetics of selenate in earthworm sub-tissues and potential bio-accessibility assessment of earthworm-derived selenium

Selenium (Se) pollution is mainly caused by anthropogenic activities, and the resulting biosecurity concerns have garnered significant attention in recent years. Using one-compartmental toxicokinetic (TK) modelling, this study explored the kinetic absorption, sub-tissue distribution, and elimination processes of the main Se species (selenate, Se(VI)) in the cultivated aerobic soil of the earthworm Eisenia fetida. The bio-accessibility of earthworm-derived Se was assessed using an in vitro simulated gastrointestinal digestion test to evaluate its potential trophic risk. The results demonstrated that Se accumulated in the pre-clitellum (PC) and total tissues (TT) of earthworms in a time- and dose-dependent manner. The highest Se levels in the PC, post-clitellum (PoC), and TT were 70.54, 57.93, and 64.26 mg/kg during the uptake phase, respectively. The kinetic Se contents in the earthworms PC and TT were consistent with the TK model but not with PoC. The earthworm TT exhibited a faster uptake (Kus = 0.83–1.02 mg/kg/day) and elimination rate of Se (Kee = 0.044–0.049 mg/kg/day), as well as a shorter half-life time (LT1/2 = 15.88–14.22 days) than PC at low soil Se levels (≤5 mg/kg). Conversely, the opposite trend was observed with higher Se concentrations (10 and 20 mg/kg). These results are likely attributable to the tissue specificity and concentration of the toxicant. Earthworms PC and TT exhibited a higher kinetic Se accumulation factor (BAFk) than steady-state BAF (BAFss), with values ranging from 8 to 24 and 3–13, respectively. Furthermore, the bio-accessibility of earthworm-derived Se to poultry ranged from 66.25 % to 84.35 %. As earthworms are at the bottom of the terrestrial food chain, the high bio-accessibility of earthworm-derived Se poses a potential risk to predators. This study offers data support and a theoretical foundation for understanding the biological footprint of soil Se and its toxicological impacts and ecological hazards.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

Plasma β-amyloid-1-42/1-40 (Aβ42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aβ42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aβ42/40 ratio (decreased in amyloid abnormal: β = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: β = 0.246, 95% CI 0.011-0.481; P-tau231: β = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (β = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (β = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (β = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. Our study suggests a possible utility of plasma Aβ42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

Residential segregation and summertime air temperature across 13 northeastern U.S. states: Potential implications for energy burden

Abstract High ambient summertime temperatures are an increasing health concern with climate change. This is a particular concern for minoritized households in the United States, for which differential energy burden may compromise adaptive capacity to high temperatures. Our research question was: Do minoritized groups experience hotter summers than the area average, and do non-Hispanic white people experience cooler summers? Using a fine-scaled spatiotemporal air temperature model and U.S. census data, we examined local (within-county) differences in warm season cooling degree days (CDDs) by ethnoracial group as a proxy for local energy demand for space cooling across states of the northeast and mid-Atlantic U.S. in 2003–2019. Using state-specific regression models adjusted for year and county, we found that Black and Latino people consistently experienced more CDDs, non-Hispanic white people experienced fewer CDDs, and Asian populations showed mixed results. We also explored a concentration-based measure of residential segregation for each ethnoracial group as one possible pathway towards temperature disparities. We included the segregation measure as a smooth term in a regression model adjusted for county and year. The results were nonlinear, but higher concentrations of white people were associated with lower annual CDDs and higher concentrations of Latino people were associated with higher annual CDDs than the county average. Concentrations for Black and Asian people were nonmonotonic, sometimes with bowed associations. These findings suggest that present-day residential segregation, as modeled by spatially smoothed ethnoracial subgroup concentrations, may contribute to summertime air temperature disparities and influence adaptive capacity. We hope these findings can support place-based interventions, including targeting of energy insecurity relief programs.

Serial block-face scanning electron microscopy of adherent cells on thin plastic substrate

Abstract Serial block-face (SBF) scanning electron microscopy (SEM) is used for imaging the entire internal ultrastructure of cells, tissue samples or small organisms. Here, we present a workflow for SBF SEM of adherent cells, such as Giardia parasites and HeLa cells, attached to the surface of a plastic culture dish, which preserves the interface between cells and plastic substrate. Cells were embedded in situ on their substrate using silicone microwells and were mounted for cross-sectioning which allowed SBF imaging of large volumes and many cells. A standard sample preparation and embedding protocol for thin section electron microscopy provided already sufficient resolution and image quality to visualize larger structures. To improve resolution and image quality of SBF imaging, we stepwise tested modifications of the protocol, such as the moderate increase of the heavy metal content of the sample. Modifications of the embedding by either the reduction of the resin layer (minimal embedding) or the addition of silver colloid to the resin were evaluated at high and low vacuum imaging conditions. The optimized sample preparation protocol is very similar to the standard preparation protocol for thin section electron microscopy, so that the samples can also be used for this application. The protocol applies a higher concentration of osmium tetroxide, a higher temperature for heavy metal incubation and an additional lead en bloc staining. In summary, the presented workflow provides a generic and adaptable solution for studying adherent cells by SBF SEM.

Comparative Analysis of Myokines and Bone Metabolism Markers in Prepubertal Vegetarian and Omnivorous Children

The role of bone and muscle as endocrine organs may be important contributing factors for children’s growth and development. Myokines, secreted by muscle cells, play a role in regulating bone metabolism, either directly or indirectly. Conversely, markers of bone metabolism, reflecting the balance between bone formation and bone resorption, can also influence myokine secretion. This study investigated a panel of serum myokines and their relationships with bone metabolism markers in children following vegetarian and omnivorous diets. A cohort of sixty-eight healthy prepubertal children, comprising 44 vegetarians and 24 omnivores, participated in this study. Anthropometric measurements, dietary assessments, and biochemical analyses were conducted. To evaluate the serum concentrations of bone markers and myokines, an enzyme-linked immunosorbent assay (ELISA) was used. The studied children did not differ regarding their serum myokine levels, except for a higher concentration of decorin in the vegetarian group (p = 0.020). The vegetarians demonstrated distinct pattern of bone metabolism markers compared to the omnivores, with lower levels of N-terminal propeptide of type I procollagen (P1NP) (p = 0.001) and elevated levels of C-terminal telopeptide of type I collagen (CTX-I) (p = 0.018). Consequently, the P1NP/CTX-I ratio was significantly decreased in the vegetarians. The children following a vegetarian diet showed impaired bone metabolism with reduced bone formation and increased bone resorption. Higher levels of decorin, a myokine involved in collagen fibrillogenesis and essential for tissue structure and function, may suggest a potential compensatory mechanism contributing to maintaining bone homeostasis in vegetarians. The observed significant positive correlations between myostatin and bone metabolism markers, including P1NP and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), suggest an interplay between muscle and bone metabolism, potentially through the RANK/RANKL/OPG signaling pathway.

Monitoring of soil pollution with heavy metals using some microbiological parameters

ABSTRACT Although heavy metal pollution significantly impacts living organisms, the monitoring biomarkers can guide remediation. This study examined the response of Pb²⁺, Cd²⁺, Cu²⁺, Zn²⁺, Cr⁶⁺, Ni²⁺, and Hg²⁺ to soil microorganisms. Bacterial counts were measured at three metal concentrations (T₁, T₂, and T₃). Results revealed that Hg²⁺-T₁ caused a 91.4% reduction in bacterial counts within 10 days, while the other metals reduced counts by 32.9% to 71.8%. Higher concentrations (T₂ and T₃) of all metals, except Ni²⁺ (48.8%) at T₂, reduced counts by 92.1% to 99.6%. After 40 days, reductions were 74.5% for Hg²⁺-T₁, 97.0% for Cr6+-T2 , and 95.2 to 98.0 % for Hg2+, Cr6+, Cu2+ and Zn2+-T3 . Intrinsically resistant bacteria were observed after 40 days, constituting 34.2%–71.8% in T₁ of most metals, except Hg²⁺ (25.5%). These percentages decreased in T2 and T3 . 55.3% of the initial organic-N was oxidized after 20 days in untreated soil, while Pb²⁺ was the least toxic for ammonification, and Hg²⁺ was the highest. In untreated soil, 67.4% of ammoniacal-N was oxidized after 20 days. Nitrification was unaffected by T₁, except for Hg²⁺. At T₂, Hg²⁺, Ni²⁺, and Cd²⁺ were the most suppressive, while at T₃, Hg²⁺, Zn²⁺, and Cd²⁺ showed the most harmful effects.

Spatial and cumulative organochlorine and mercury exposure assessments in Steller Sea lions of Alaska: Emphasizing pups

Steller sea lions (SSL) are sentinels for monitoring environmental contaminants in remote areas of the Aleutian Islands, Alaska. Therefore, concentrations of several organochlorines (OCs) were measured in blood from 123 SSL pups sampled from 3 regions; the western Aleutian Islands (WAI), central Aleutian Islands (CAI), and the central Gulf of Alaska. Blood, blubber, and milk from 12 adult female SSL from WAI, CAI and southeast Alaska also were analyzed. Findings included the following. SSL pups had higher concentrations of some OCs and mercury (Hg) on rookeries in the WAI than those more easterly. Pups had significantly higher blood concentrations of many OC classes than adult females sampled within the same region; some pups had PCB concentrations exceeding thresholds of concern (∑PCBs >8600 ng/g lw). ∑PCB concentration in pup whole blood was positively correlated with the trophic marker, δ15N within the regions sampled, along with two PCB congeners (PCB138 and PCB153). This suggests that the dams of pups with higher ∑PCBs, PCB138, and PCB153 concentrations were feeding on more predatory prey. Adult female blubber ∑DDT and hexachlorocyclohexane concentrations were also positively correlated with δ15N values. Several pups (mostly from WAI) had blood Hg concentrations and/or blood PCB concentrations (surrogate for overall OC exposures) of concern. The finding that WAI SSL pups have been exposed to multiple contaminants calls for future investigation of their cumulative exposure to a mixture of contaminants especially their transplacental and then transmammary exposure routes.

Harnessing Walnut-Based Zinc Oxide Nanoparticles: A Sustainable Approach to Combat the Disease Complex of Meloidogyne arenaria and Macrophomina phaseolina in Cowpea

Zinc oxide nanoparticles (ZnO NPs) exhibit diverse applications, including antimicrobial, UV-blocking, and catalytic properties, due to their unique structure and properties. This study focused on the characterization of zinc oxide nanoparticles (ZnO NPs) synthesized from Juglans regia leaves and their application in mitigating the impact of simultaneous infection by Meloidogyne arenaria (root-knot nematode) and Macrophomina phaseolina (root-rot fungus) in cowpea plants. The characterization of ZnO NPs was carried out through various analytical techniques, including UV–visible spectrophotometry, Powder-XRD analysis, FT-IR spectroscopy, and SEM-EDX analysis. The study confirmed the successful synthesis of ZnO NPs with a hexagonal wurtzite structure and exceptional purity. Under in vitro conditions, ZnO NPs exhibited significant nematicidal and antifungal activities. The mortality of M. arenaria juveniles increased with rising ZnO NP concentrations, and a similar trend was observed in the inhibition of M. phaseolina mycelial growth. SEM studies revealed physical damage to nematodes and structural distortions in fungal hyphae due to ZnO NP treatment. In infected cowpea plants, ZnO NPs significantly improved plant growth parameters, including plant length, fresh mass, and dry mass, especially at higher concentrations. Leghemoglobin content and the number of root nodules also increased after ZnO NP treatment. Additionally, ZnO NPs reduced gall formation and egg mass production by M. arenaria nematodes and effectively inhibited the growth of M. phaseolina in the roots. Furthermore, histochemical analyses demonstrated a reduction in oxidative stress, as indicated by decreased levels of reactive oxygen species (ROS) and lipid peroxidation in ZnO NP-treated plants. These findings highlight the potential of green-synthesized ZnO NPs as an eco-friendly and effective solution to manage disease complex in cowpea caused by simultaneous nematode and fungal infections.

Assessment of polycyclic aromatic hydrocarbon (PAH) profiles in heat-processed meat and fish: a study on health risk evaluation

The profiles of polycyclic aromatic hydrocarbons (PAHs) in selected heat-processed meat and fish were evaluated to determine the potential health risk associated with consumption. The samples were analysed using a gas Chromatography-Mass spectrometer. Different concentrations of individual PAHs were detected in the samples, with the smoked samples having the highest concentrations. The total PAHs (mg/kg) in smoked samples were 2.763 ± 0.185 (game meat), 1.618 ± 0.102 (mackerel fish), and 1.718 ± 0.129 (catfish), whereas levels (mg/kg) in grilled samples were 0.771 ± 0.049 (chicken) and 0.911 ± 0.053 (fish). The total carcinogenic PAH (PAH7) concentrations (mg/kg) in grilled chicken and fish and smoked (game meat, mackerel fish, and catfish) samples were 0.231, 0.294, 0.440, 0.309, and 0.332, while their total PAH8 concentrations were 0.356, 0.371, 0.537, 0.465, and 0.476 respectively. The non-carcinogenic PAH risk estimations, both individually (hazard quotient) and cumulatively (hazard index), were below 1 in all the samples. The mean concentrations of PAH markers B[a]P and the PAH4 were above the EU limits in both the smoked and the grilled samples tested. This implies that exposure to high levels of these PAHs through regular consumption of these products may increase the risk of developing certain types of cancer and other health issues. The smoked fishes has the lowest MOE values for the PAH8 compared to the other samples. The margin of exposures (MOEs), carcinogenic toxic equivalent (TEQ), and excess cancer risk (ECR) also indicated that frequent consumption of smoked fish (mackerel or catfish) by an adult of 70 kg body weight above the reported intake rate of 0.0019 kg/AME/day for a prolonged period may have higher cancer risks than in other samples. Smoked game meat had the highest PAH16 level, but indicated a relatively lower risk level, possibly because of its relatively low intake rate (0.0004 kg/AME/day).