Simultaneous immobilization of multiple heavy metal(loid)s in contaminated water and alkaline soil inoculated Fe/Mn oxidizing bacterium.

Two strains of Fe/Mn oxidizing bacteria tolerant to high concentrations of multiple heavy metal(loid)s and efficient decontamination for them were screened. The surface of the bio-Fe/Mn oxides produced by the oxidation of Fe(II) and Mn(II) by Pseudomonas taiwanensis (marked as P4) and Pseudomonas plecoglossicida (marked as G1) contains rich reactive oxygen functional groups, which play critical roles in the removal efficiency and immobilization of heavy metal(loid)s in co-contamination system. The isolated strains P4 and G1 can grow well in the following environments: pH 5-9, NaCl 0-4%, and temperature 20-30°C. The removal efficiencies of Fe, Pb, As, Zn, Cd, Cu, and Mn are effective after inoculation of the strains P4 and G1 in the simulated water system (the initial concentrations of heavy metal(loid) were 1 mg/L), approximately reaching 96%, 92%, 85%, 67%, 70%, 54% and 15%, respectively. The exchangeable and carbonate bound As, Cd, Pb and Cu are more inclined to convert to the Fe-Mn oxide bound fractions in P4 and G1 treated soil, thereby reducing the phytoavailability and bioaccessible of heavy metal(loid)s. This research provides alternatives method to treat water and soil containing high concentrations of multi-heavy metal(loid)s.

Real-time observation of a metal complex-driven reaction intermediate using a porous protein crystal and serial femtosecond crystallography.

Determining short-lived intermediate structures in chemical reactions is challenging. Although ultrafast spectroscopic methods can detect the formation of transient intermediates, real-space structures cannot be determined directly from such studies. Time-resolved serial femtosecond crystallography (TR-SFX) has recently proven to be a powerful method for capturing molecular changes in proteins on femtosecond timescales. However, the methodology has been mostly applied to natural proteins/enzymes and limited to reactions promoted by synthetic molecules due to structure determination challenges. This work demonstrates the applicability of TR-SFX for investigations of chemical reaction mechanisms of synthetic metal complexes. We fix a light-induced CO-releasing Mn(CO)3 reaction center in porous hen egg white lysozyme (HEWL) microcrystals. By controlling light exposure and time, we capture the real-time formation of Mn-carbonyl intermediates during the CO release reaction. The asymmetric protein environment is found to influence the order of CO release. The experimentally-observed reaction path agrees with quantum mechanical calculations. Therefore, our demonstration offers a new approach to visualize atomic-level reactions of small molecules using TR-SFX with real-space structure determination. This advance holds the potential to facilitate design of artificial metalloenzymes with precise mechanisms, empowering design, control and development of innovative reactions.

[Quantitative Activity-Induced Manganese-Enhanced Magnetic Resonance Imaging: Principles, Applications, and Limitations].

Accurate identification of regions that show activity changes in response to functional expression is necessary to understand the mechanisms underlying functional expression in the brain. Quantitative activity-induced manganese-enhanced magnetic resonance imaging (qAIM-MRI) is a noninvasive whole-brain activity history imaging method used for this purpose. Notably, qAIM-MRI is a pseudo-Ca2+ imaging method that uses Mn2+ as a surrogate marker for Ca2+. In this paper, I describe the principles, applications, and limitations of qAIM-MRI.

Serum macroelements and microelements levels in periparturient dairy cows in relation to fatty liver diseases.

BACKGROUND: Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows. RESULTS: A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows. CONCLUSIONS: Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur.

Background: The development of autism spectrum disorder (ASD) may stem from exposure to environmental pollutants such as heavy metals. The primary objective of this study is to determine the role of heavy metals of concern such as manganese (Mn), cadmium (Cd), lead (Pb), arsenic (As), and essential trace element selenium (Se) among ASD children in Kuala Lumpur, Malaysia. Method: A total of 155 preschoolers in Kuala Lumpur between the ages 3 to 6 participated in an unmatched case-control study, comprising ASD children (n = 81) recruited from an early intervention program for autism, and 74 children without autism who were recruited from public preschools. Urine samples were collected at home, delivered to the study site, and transported to the environmental lab within 24 hours. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to measure the concentration of heavy metals in the samples. Data were analysed using bivariate statistical tests (Chi-square and T-test) and logistic regression models. Result: This study demonstrated that Cd, Pb, and As urine levels were significantly greater in children without autism relative to those affected with ASD (p < 0.05). No significant difference was in the levels of Se (p = 0.659) and Mn (p = 0.875) between children with ASD and the control group. The majority of children in both groups have urine As, Pb, and Cd values lower than 15.1 µg/dL, 1.0 µg/dL, and 1.0 µg/dL, respectively which are the minimal risk values for noncarcinogenic detrimental human health effect due to the heavy metal's exposure . Factors associated with having an ASD child included being a firstborn, male, and higher parental education levels (adjusted odds ratios (aOR) > 1, p < 0.05). Conclusion: Preschoolers in this study demonstrated low levels of heavy metals in their urine samples, which was relatively lower in ASD children compared to the healthy matched controls. These findings may arise from the diminished capacity to excrete heavy metals, especially among ASD children, thereby causing further accumulation of heavy metals in the body. These findings, including the factors associated with having an ASD child, may be considered by healthcare professionals involved in child development care, for early ASD detection. Further assessment of heavy metals among ASD children in the country and interventional studies to develop effective methods of addressing exposure to heavy metals will be beneficial for future reference.

Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.

Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn2+), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro: promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.

Synergistic solidification and mechanism research of electrolytic manganese residue and coal fly ash based on C-A-S-H gel material.

Electrolytic manganese residue (EMR) is known for high concentrations of Mn2+, NH4+, and heavy metals. Failure to undergo benign treatment and landfill disposal would undeniably lead to negative impacts on the quality of the surrounding ecological environment. This study sought to mitigate the latent environmental risks associated with EMR using a cooperative solidification/stabilization (S/S) method involving coal fly ash (CFA). Leveraging leaching toxicity tests, the leaching behavior of pollutants in electrolytic manganese residue-based geopolymer materials (EMRGM) was determined. At the same time, mechanistic insights into S/S processes were explored utilizing characterization techniques such as XRF, XRD, FT-IR, SEM-EDS, and XPS. Those results confirmed significant reductions in the leaching toxicities of Mn2+ and NH4+ to 4.64 µg/L and 0.99 mg/L, respectively, with all other heavy metal ions falling within the permissible limits set by relevant standards. Further analysis shows that most of NH4+ volatilizes into the air as NH3, and a small part is fixed in the EMRGM in the form of struvite; in addition to being oxidized to MnOOH and MnO2, Mn2+ will also be adsorbed and wrapped by silicon-aluminum gel together with other heavy metal elements in the form of ions or precipitation. This research undeniably provides a solid theoretical foundation for the benign treatment and resourceful utilization of EMR and CFA, two prominent industrial solid wastes.

Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition.

Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting superoxide (O2●-) to molecular oxygen (O2) and hydrogen peroxide (H2O2) with proton-coupled electron transfers (PCETs). Human MnSOD has evolved to be highly product inhibited to limit the formation of H2O2, a freely diffusible oxidant and signaling molecule. The product-inhibited complex is thought to be composed of a peroxide (O22-) or hydroperoxide (HO2-) species bound to Mn ion and formed from an unknown PCET mechanism. PCET mechanisms of proteins are typically not known due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the mechanism, we combine neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states of the enzyme to reveal the positions of all the atoms, including hydrogen, and the electronic configuration of the metal ion. The data identifies the product-inhibited complex, and a PCET mechanism of inhibition is constructed.

Mesoporous Oxidized Mn-Ca Nanoparticles as Potential Antimicrobial Agents for Wound Healing.

Managing chronic non-healing wounds presents a significant clinical challenge due to their frequent bacterial infections. Mesoporous silica-based materials possess robust wound-healing capabilities attributed to their renowned antimicrobial properties. The current study details the advancement of mesoporous silicon-loaded MnO and CaO molecules (HMn-Ca) against bacterial infections and chronic non-healing wounds. HMn-Ca was synthesized by reducing manganese chloride and calcium chloride by urotropine solution with mesoporous silicon as the template, thereby transforming the manganese and calcium ions on the framework of mesoporous silicon. The developed HMn-Ca was investigated using scanning electron microscopy (SEM), transmission electron microscope (TEM), ultraviolet-visible (UV-visible), and visible spectrophotometry, followed by the determination of Zeta potential. The production of reactive oxygen species (ROS) was determined by using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction. The wound healing effectiveness of the synthesized HMn-Ca is evaluated in a bacterial-infected mouse model. The loading of MnO and CaO inside mesoporous silicon enhanced the generation of ROS and the capacity of bacterial capture, subsequently decomposing the bacterial membrane, leading to the puncturing of the bacterial membrane, followed by cellular demise. As a result, treatment with HMn-Ca could improve the healing of the bacterial-infected wound, illustrating a straightforward yet potent method for engineering nanozymes tailored for antibacterial therapy.

The Role of Ovalbumin in Manganese Homeostasis during Chick Embryogenesis: An EPR Spectroscopic Study.

Ovalbumin (OVA), a protein vital for chick embryo nutrition, hydration, and antimicrobial protection, together with other egg-white proteins, migrates to the amniotic fluid and is orally absorbed by the embryo during embryogenesis. Recently, it has been shown that for optimal eggshell quality, the hen diet can be supplemented with manganese. Although essential for embryonic development, manganese in excess causes neurotoxicity. This study investigates whether OVA may be involved in the regulation of manganese levels. The binding of Mn(II) to OVA was investigated using electron paramagnetic resonance (EPR) spectroscopy. The results show that OVA binds a maximum of two Mn(II) ions, one with slightly weaker affinity, even in a 10-fold excess, suggesting it may have a protective role from Mn(II) overload. It seems that the binding of Mn(II), or the presence of excess Mn(II), does not affect OVA's tertiary structure, as evidenced from fluorescence and UV/vis measurements. Comparative analysis with bovine and human serum albumins revealed that they exhibit higher affinities for Mn(II) than OVA, most likely due to their essentially different physiological roles. These findings suggest that OVA does not play a role in the transport and storage of manganese; however, it may be involved in embryo protection from manganese-induced toxicity.

Trace elements in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PCA) is an extremely aggressive malignant cancer with an increasing incidence and a low five-year survival rate. The main reason for this high mortality is that most patients are diagnosed with PCA at an advanced stage, missing early treatment options and opportunities. As important nutrients of the human body, trace elements play an important role in maintaining normal physiological functions. Moreover, trace elements are closely related to many diseases, including PCA. REVIEW: This review systematically summarizes the latest research progress on selenium, copper, arsenic, and manganese in PCA, elucidates their application in PCA, and provides a new reference for the prevention, diagnosis and treatment of PCA. CONCLUSION: Trace elements such as selenium, copper, arsenic and manganese are playing an important role in the risk, pathogenesis, diagnosis and treatment of PCA. Meanwhile, they have a certain inhibitory effect on PCA, the mechanism mainly includes: promoting ferroptosis, inducing apoptosis, inhibiting metastasis, and inhibiting excessive proliferation.

Bimetallic porous Mn/Co oxide nanosheets with efficient oxidase-mimicking activity for the sensitive colorimetric determination of resveratrol in different matrices.

BACKGROUND: Resveratrol, a natural polyphenol compound used as an ingredient in dietary supplements, and pharmaceuticals, has gained significant attention due to its potential health benefits. However, the accurate and sensitive determination of resveratrol in complex matrices remains a challenge. In this study, we propose the utilization of bimetallic porous Mn/Co oxide nanosheets (MnCoO-NSs) as catalysts for the colorimetric determination of resveratrol. RESULTS: The bimetallic porous MnCoO-NSs were prepared through a facile one-stone-two-birds strategy. These nanosheets exhibited superior oxidase-mimicking activity, as evidenced by the catalytic oxidation of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB), producing a blue-colored oxTMB species with a prominent absorbance peak at 655 nm. The catalytic activity was promoted through the production of superoxide anion (O2•-), which enhanced the affinity of MnCoO-NSs to the TMB molecules. Upon the addition of resveratrol, the oxidation process was inhibited, resulting in rapid fading of the blue color. This colorimetric sensing platform exhibited a linear response to resveratrol concentrations over the range of 2.2-87.6 µM, with a limit of detection of 0.210 µM. The method was further applied for the determination of resveratrol in different matrices including biological fluids, pharmaceuticals, and environmental water. SIGNIFICANCE: The utilization of these MnCoO-NSs offers a simple and cost-effective alternative to conventional analytical techniques for the determination of resveratrol. Their high sensitivity, selectivity, and stability enable accurate measurements of resveratrol in various complex matrices. This research has implications in areas such as pharmaceutical analysis, biomedical research, and environmental analysis, where the reliable determination of resveratrol is crucial for assessing its therapeutic potential and ensuring product quality.

Adjusting luminescence properties of ZnAl2O4:Mn2+(Mn4+), Li+ phosphors through cation substitution.

ZnAl2O4 with a typical spinel structure is highly expected to be a novel rare-earth-free ion-activated oxide phosphor with red emission, which holds high actual meaning for advancing phosphor-converted light-emitting diode (pc-LED) lighting. Among the rare-earth-free activators, Mn4+ ions have emerged as one of the most promising activators. Considering the price advantage of MnCO3 generating Mn2+ ions and the charge compensation effect potentially obtaining Mn4+ ions from Mn2+ ions, this research delves into a collection of ZnAl2O4:Mn2+(Mn4+), x Li+ (x = 0%-40%) phosphors with Li+ as co-dopant and MnCO3 as Mn2+ dopant source prepared by a high temperature solid-state reaction method. The lattice structure was investigated using X-ray diffraction (XRD), photoluminescence (PL), and photoluminescence excitation (PLE) spectroscopy. Results suggest a relatively high probability of Li+ ions occupying Zn2+ lattice sites. Furthermore, Li+ ion doping was assuredly found to facilitate the oxidization of Mn2+ to Mn4+, leading to a shift of luminescence peak from 516 to 656 nm. An intriguing phenomenon that the emission color changed with the Li+ doping content was also observed. Meanwhile, the luminescence intensity and quantum yield (QY) at different temperatures, as well as the relevant thermal quenching mechanism, were determined and elucidated detailedly.

Effect and mechanism of Mn2+ on urease activity during anaerobic biological treatment of landfill leachate.

As a crucial hydrolytic enzyme, urease plays a vital role in anaerobic biological treatment. It is well-known that manganese ions are abundant in landfill leachate, but their concentration fluctuates significantly. However, few studies have investigated the effect and mechanism of different concentrations of Mn2+ on urease activity during anaerobic biological treatment of landfill leachate. This paper aimed to investigate the effects and mechanisms of different concentrations of Mn2+ on urease activity. The results showed that an appropriate amount of Mn2+ could significantly enhance urease activity, while a high concentration of Mn2+ could inhibit it. Insight into the mechanisms behind this phenomenon, various methods such as Zeta potential, particle size, ultraviolet spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, and statistical analysis were employed in our study. Research suggested that, on one hand, Mn2+ may form hydrogen bonds with the side chain amino or carboxyl groups of urease amino acid residues, affecting the structure of urease through hydrogen bonding. Additionally, Mn2+ also binds to urease through hydrophobic interactions. On the other hand, the C-OH and C-N functional groups in urease have a strong affinity for Mn2+, and changes in these functional groups can greatly enhance the activity of urease. Furthermore, under the action of high concentrations of Mn2+, while the structure of urease becomes more stable, there is also a steric hindrance phenomenon that affects the substrate from entering the catalytic center. Therefore, studying the mechanism of Mn2+ affecting urease activity has significant biological significance and provides a new perspective for exploring the impact of metals on anaerobic bioprocessing of landfill leachate.

Study on harmless treatment of electrolytic manganese residue by low temperature thermochemical method.

The Electrolytic Manganese Residue (EMR) is a by-product of the electrolytic manganese metal (EMM) industry, containing high concentrations of potential pollutants such as NH4+-N and soluble Mn2+. These components pose a serious threat to the ecological environment. To explore accurate, efficient, and harmless treatment methods for EMR, this study proposes a low-temperature thermochemical approach. The orthogonal experiment design investigates the effects of reaction temperature, reaction time, quicklime (CaO), sodium carbonate (Na2CO3), sodium phosphate (Na3PO4) (Reviewer #3), and water consumption on manganese solidified and ammonia removal from EMR. The results indicate that optimal conditions are a reaction temperature of 60 ℃ (Reviewer #3) and a reaction time of 10 min. CaO precipitates Mn2+ as manganese hydroxide (Mn(OH)2) (Reviewer #3), achieving effective manganese solidified and ammonia removal. The addition of Na2CO3 causes Mn2+ to form manganesecarbonate (MnCO3) (Reviewer #3)precipitate, while Na3PO4 makes Mn2+ form Manganese phosphate trihydrate (Mn3(PO4)2·3H2O) (Reviewer #3). Increased water consumption enhances the interaction adequacy between ions. Under optimal conditions (CaO 10%, Na2CO3 1%, Na3PO4 0.5%, and 80% water consumption), the removal rate of ammonium ions reaches 98.5%, and the solidification rate of soluble Mn2+ is 99.9%. The order of influence on ammonium ion removal is CaO > water consumption > Na3PO4 > Na2CO3. Therefore, this study provides a new method for low-cost process disposal and efficient harmless treatment of EMR (Reviewer #3).

The mechanism of arbuscular mycorrhizal fungi-alleviated manganese toxicity in plants: A review.

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research.

Formation of Biogenic Manganese Oxide Nodules on Hyphae of a New Fungal Isolate of Periconia That Immobilizes Aqueous Copper.

Mn(II)-oxidizing microorganisms are considered to play significant roles in the natural geochemical cycles of Mn and other heavy metals because the insoluble biogenic Mn oxides (BMOs) that are produced by these microorganisms adsorb other dissolved heavy metals and immobilize them as precipitates. In the present study, a new Mn(II)-oxidizing fungal strain belonging to the ascomycete genus Periconia, a well-studied plant-associating fungal genus with Mn(II)-oxidizing activity that has not yet been exami-ned in detail, was isolated from natural groundwater outflow sediment. This isolate, named strain TS-2, was confirmed to oxidize dissolved Mn(II) and produce insoluble BMOs that formed characteristic, separately-located nodules on their hyphae while leaving major areas of the hyphae free from encrustation. These BMO nodules also adsorbed and immobilized dissolved Cu(II), a model analyte of heavy metals, as evidenced by elemental mapping ana-lyses of fungal hyphae-BMO assemblages using a scanning electron microscope with energy-dispersive X-ray spectroscopy (SEM-EDX). Analyses of functional genes within the whole genome of strain TS-2 further revealed the presence of multiple genes predicted to encode laccases/multicopper oxidases that were potentially responsible for Mn(II) oxidation by this strain. The formation of BMO nodules may have functioned to prevent the complete encrustation of fungal hyphae, thereby enabling the control of heavy metal concentrations in their local microenvironments while maintaining hyphal functionality. The present results will expand our knowledge of the physiological and morphological traits of Mn(II)-oxidizing Periconia, which may affect the natural cycle of heavy metals through their immobilization.

Manganese porphyrin-based treatment improves fetal-placental development and protects against oxidative damage and NLRP3 inflammasome activation in a rat maternal hypothyroidism model.

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1ß, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.

Investigating the Interplay of Toxic Metals and Essential Elements in Liver Disease.

Liver diseases, including non-alcoholic fatty liver disease (NAFLD), are a growing global health issue. Environmental exposure to toxic metals can harm the liver, increasing the risk of NAFLD. Essential elements are vital for liver health, but imbalances or deficiencies can contribute to the development of NAFLD. Therefore, understanding the interplay between toxic metals and essential elements in liver disease is important. This study aims to assess the individual and combined effects of toxic metals (lead(Pb), cadmium (Cd), mercury (Hg)), and essential elements (manganese and selenium) on the risk of liver disease. Methods: We assessed the individual and combined effects of Pb, Cd, Hg, manganese (Mn), and selenium (Se) on liver disease risk using data from the National Health and Nutrition Examination Survey between 2017 and 2018. We performed descriptive statistics and linear regression analysis and then utilized Bayesian Kernel Machine Regression (BKMR) techniques such as univariate, bivariate, and overall effect analysis. BKMR enabled the assessment of non-linear exposure-response functions and interactions between metals and essential elements. Posterior Inclusion Probabilities (PIPs) were calculated to determine the importance of each metal and essential element in contributing to liver disease. Regarding our study results, the regression analysis of liver injury biomarkers ALT, AST, ALP, GGT, total bilirubin, and the FLI-an indicator of NAFLD-with toxic metals and essential elements, adjusting for covariates such as age, sex, BMI, alcohol consumption, ethnicity, income, and smoking status, demonstrated the differential effects of these contaminants on the markers of interest. Our BKMR analysis provided further insights. For instance, the PIP results underscored Pb's consistent importance in contributing to liver disease (PIP = 1.000), followed by Hg (PIP = 0.9512), Cd (PIP = 0.5796), Se (PIP = 0.5572), and Mn (PIP = 0.4248). Our univariate analysis showed a positive trend with Pb, while other exposures were relatively flat. Our analysis of the single-variable effects of toxic metals and essential elements on NAFLD also revealed that Pb significantly affected the risk of NAFLD. Our bivariate analysis found a positive (toxic) trend when Pb was combined with other metals and essential elements. For the overall exposure effect of exposure to all the contaminants together, the estimated risk of NAFLD showed a steady increase from the 60th to the 75th percentile. In conclusion, our study indicates that Pb exposure, when combined with other toxic metals and essential elements, plays a significant role in bringing about adverse liver disease outcomes.

Encapsulated Mn-Saturated Lactoferrin as a Safe Source of Manganese Ions for Restoring Probiotic Lactobacillus plantarum.

The growth of Lactobacillus plantarum, a member of the Lactobacillus genus, which plays a crucial role in the bacterial microbiome of the gut, is significantly influenced by manganese ions. They can be safely delivered to the intestines by exploiting the chelating abilities of lactoferrin. The aim of this work was to encapsulate lactoferrin saturated with manganese ions (MnLf) in a system based on the Eudragit® RS polymer to protect protein from degradation and manganese release in the gastric environment. The entrapment efficiency was satisfactory, reaching about 95%, and most importantly, manganese ions were not released during microparticles (MPs) formation. The release profile of the protein from the freshly prepared MPs was sustained, with less than 15% of the protein released within the first hour. To achieve similar protein release efficiency, freeze-drying was carried out in the presence of 10% (w/v) mannitol as a cryoprotectant for MPs frozen at -20 °C. MPs with encapsulated MnLf exhibited prebiotic activity towards Lactobacillus plantarum. More importantly, the presence of equivalent levels of manganese ions in free form in the medium, as well as chelating by lactoferrin encapsulated in MPs, had a similar impact on stimulating bacterial growth. This indicates that the bioavailability of manganese ions in our prepared system is very good.