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Journal of Oleo Science Oct 2023In this study, we analyzed the properties of amphiphilic alkyldi(methoxy poly(ethylene glycol) (MePEG)350-lactate) phosphates based on ethyl lactate, the monomethyl...
In this study, we analyzed the properties of amphiphilic alkyldi(methoxy poly(ethylene glycol) (MePEG)350-lactate) phosphates based on ethyl lactate, the monomethyl ether of poly(ethylene glycol)350, and alkyldichloro phosphates. Interestingly, these triesters combine two biodegradable bonds, -P(O)-O-C and -C(O)-O-C-, and include hydrophilic (MePEG350-lactate) and hydrophobic (R-aliphatic chain of alcohols) moieties. The properties of these esters resemble those of phospholipids. After being placed in an aqueous solution, they self-assembled. We also determined the effects of ester composition on micelle formation, stability, and size using dynamic light scattering. Solubilization tests using Sudan III or doxorubicin hydrochloride (Dox·HCl) revealed that they could be incorporated into the hydrophobic cores of dodecyl di(MePEG350-lactate) phosphate and hexadecyl di(MePEG350-lactate) phosphate. Notably, dodecyl di(MePEG350-lactate) phosphate was stable for five days, whereas hexadecyl di(MePEG350-lactate) phosphate was stable for seven days in phosphate-buffered saline. Moreover, Dox·HCl release rates from the micelles were approximately 30-40, 70-80, and 90-100% after 1, 5, and 28 d, respectively.
Topics: Micelles; Polyethylene Glycols; Doxorubicin; Phosphates; Lactates; Drug Carriers
PubMed: 37704442
DOI: 10.5650/jos.ess23108 -
Biotechnology Advances Nov 2023Cyanotoxins are by definition "harmful agents" produced by cyanobacteria. Their toxicity has been extensively studied and reviewed over the years. Cyanotoxins have been... (Review)
Review
Cyanotoxins are by definition "harmful agents" produced by cyanobacteria. Their toxicity has been extensively studied and reviewed over the years. Cyanotoxins have been commonly classified, based on their poisonous effects on mammals, into three main classes, neurotoxins, hepatotoxins and dermatotoxins, and, considering their chemical features, mainly identified as peptides, alkaloids and lipopolysaccharides. Here we propose a broader subdivision of cyanotoxins into eight distinct classes, taking into account their molecular structures, biosynthesis and modes of action: alkaloids, non-ribosomal peptides, polyketides, non-protein amino acids, indole alkaloids, organophosphates, lipopeptides and lipoglycans. For each class, the structures and primary mechanisms of toxicity of the main representative cyanotoxins are reported. Despite their powerful biological activities, only recently scientists have considered the biotechnological potential of cyanotoxins, and their applications both in medical and in industrial settings, even if only a few of these have reached the biotech market. In this perspective, we discuss the potential uses of cyanotoxins as anticancer, antimicrobial, and biocidal agents, as common applications for cytotoxic compounds. Furthermore, taking into account their mechanisms of action, we describe peculiar potential bioactivities for several cyanotoxin classes, such as local anaesthetics, antithrombotics, neuroplasticity promoters, immunomodulating and antifouling agents. In this review, we aim to stimulate research on the potential beneficial roles of cyanotoxins, which require interdisciplinary cooperation to facilitate the discovery of innovative biotechnologies.
Topics: Animals; Cyanobacteria Toxins; Bacterial Toxins; Microcystins; Cyanobacteria; Alkaloids; Mammals
PubMed: 37567398
DOI: 10.1016/j.biotechadv.2023.108235 -
World Journal of Clinical Cases Aug 2023Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of... (Review)
Review
Alzheimer's disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta, and protein phosphatase-2A. Moreover, it altered the expression of the microtubule associated protein tau gene, and changed levels of intracellular calcium. These changes affected tau protein phosphorylation and neuroinflammation, and also increased oxidative stress. In addition, the exposed subjects had poor level of performance in tests that involved evaluation of novelty, as test on verbal, non-verbal, spatial memory, attention, and problem-solving skills.
PubMed: 37727721
DOI: 10.12998/wjcc.v11.i24.5628 -
Nature Communications Aug 2023Genomic structural variation (SV) has profound effects on organismal evolution; often serving as a source of novel genetic variation. Gene copy number variation (CNV),...
Genomic structural variation (SV) has profound effects on organismal evolution; often serving as a source of novel genetic variation. Gene copy number variation (CNV), one type of SV, has repeatedly been associated with adaptive evolution in eukaryotes, especially with environmental stress. Resistance to the widely used herbicide, glyphosate, has evolved through target-site CNV in many weedy plant species, including the economically important grass, Eleusine indica (goosegrass); however, the origin and mechanism of these CNVs remain elusive in many weed species due to limited genetic and genomic resources. To study this CNV in goosegrass, we present high-quality reference genomes for glyphosate-susceptible and -resistant goosegrass lines and fine-assembles of the duplication of glyphosate's target site gene 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). We reveal a unique rearrangement of EPSPS involving chromosome subtelomeres. This discovery adds to the limited knowledge of the importance of subtelomeres as genetic variation generators and provides another unique example for herbicide resistance evolution.
Topics: Eleusine; 3-Phosphoshikimate 1-Carboxyvinyltransferase; DNA Copy Number Variations; Phosphates; Glyphosate
PubMed: 37567866
DOI: 10.1038/s41467-023-40407-6 -
Ecotoxicology and Environmental Safety Dec 2023Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver...
Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.
Topics: Male; Mice; Animals; Non-alcoholic Fatty Liver Disease; Liver; Inflammation; Adipose Tissue; Diet, Western; Herbicides; 2,4-Dichlorophenoxyacetic Acid; Mice, Inbred C57BL; Glyphosate
PubMed: 37992649
DOI: 10.1016/j.ecoenv.2023.115688 -
Polymers May 2024Decreasing oil resources creates the need to search for raw materials in the biosphere, which can be converted into polyols suitable for obtaining polyurethane foams...
Decreasing oil resources creates the need to search for raw materials in the biosphere, which can be converted into polyols suitable for obtaining polyurethane foams (PUF). One such low-cost and reproducible biopolymer is cellulose. There are not many examples of cellulose-derived polyols due to the sluggish reactivity of cellulose itself. Recently, cellulose and its hydroxypropyl derivatives were applied as source materials to obtain polyols, further converted into biodegradable rigid polyurethane foams (PUFs). Those PUFs were flammable. Here, we describe our efforts to modify such PUFs in order to decrease their flammability. We obtained an ester from diethylene glycol and phosphoric(III) acid and used it as a reactive flame retardant in the synthesis of polyol-containing hydroxypropyl derivative of cellulose. The cellulose-based polyol was characterized by infrared spectra (IR) and proton nuclear magnetic resonance (H-NMR) methods. Its properties, such as density, viscosity, surface tension, and hydroxyl numbers, were determined. Melamine was also added to the foamed composition as an additive flame retardant, obtaining PUFs, which were characterized by apparent density, water uptake, dimension stability, heat conductance, compressive strength, and heat resistance at 150 and 175 °C. Obtained rigid PUFs were tested for flammability by determining oxygen index, horizontal flammability test, and calorimetric analysis. Obtained rigid PUFs showed improved flammability resistance in comparison with non-modified PUFs and classic PUFs.
PubMed: 38794632
DOI: 10.3390/polym16101438 -
Ecotoxicology and Environmental Safety Sep 2023Heavy metals are pervasive pollutants found in water, soil, and solid wastes. Bio-solidification offers an environmentally friendly approach to immobilize heavy metal... (Review)
Review
Heavy metals are pervasive pollutants found in water, soil, and solid wastes. Bio-solidification offers an environmentally friendly approach to immobilize heavy metal ions using two types of bacteria: urease-producing bacteria (UPB) and phosphatase-producing bacteria (PPB). UPB, exemplified by Sporosarcina pasteurii, secretes urease to hydrolyze urea and generate CO ions, while PPB, like Bacillus subtilis, produces alkaline phosphatase to hydrolyze organophosphate monoester (ROP) and produce PO ions. These ions react with heavy metal ions, effectively reducing their concentration by forming insoluble carbonate or phosphate precipitates. The success of bio-solidification is influenced by various factors, including substrate concentration, temperature, pH, and bacterial density. Optimal operational conditions can significantly enhance the remediation performance of heavy metals. UPB and PPB hold great potential for remediating heavy metal pollution in diverse contaminated areas such as tailings ponds, electroplating sewage, and garbage incineration plants. In conclusion, harnessing the power of these microbial methods can provide effective solutions for remediating heavy metal-induced pollution across a range of environmental conditions.
Topics: Urease; Metals, Heavy; Phosphates; Organophosphates; Bacillus subtilis; Soil Pollutants; Soil
PubMed: 37517309
DOI: 10.1016/j.ecoenv.2023.115305 -
Environmental Health Perspectives Nov 2023Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence of the negative impacts of contemporary use insecticides on sperm concentration has increased over the last few decades; however, meta-analyses on this topic are rare.
OBJECTIVES
This investigation assessed the qualitative and quantitative strength of epidemiological evidence regarding adult exposure to two classes of contemporary use insecticides-organophosphates (OPs) and -methyl carbamates (NMCs)-and sperm concentration using robust and reproducible systematic review and meta-analysis methods.
METHODS
Three scientific databases (PubMed, Scopus, and Web of Science), two U.S. government databases (NIOSHTIC-2 and Science.gov), and five nongovernmental organization websites were searched for relevant primary epidemiological studies published in any language through 11 August 2022. Risk of bias and strength of evidence were evaluated according to Navigation Guide systematic review methodology. Bias-adjusted standardized mean difference effect sizes were calculated and pooled using a three-level, multivariate random-effect meta-analysis model with cluster-robust variance estimation.
RESULTS
Across 20 studies, 21 study populations, 42 effect sizes, and 1,774 adult men, the pooled bias-adjusted standardized mean difference in sperm concentration between adult men more- and less-exposed to OP and NMC insecticides was (95% CI: , ; ). Sensitivity and subgroup analyses explored statistical heterogeneity and validated the model robustness. Although the pooled effect estimate was modified by risk of bias, insecticide class, exposure setting, and recruitment setting, it remained negative in direction across all meta-analyses. The body of evidence was rated to be of moderate quality, with sufficient evidence of an association between higher adult OP and NMC insecticide exposure and lower sperm concentration.
DISCUSSION
This comprehensive investigation found sufficient evidence of an association between higher OP and NMC insecticide exposure and lower sperm concentration in adults. Although additional cohort studies can be beneficial to fill data gaps, the strength of evidence warrants reducing exposure to OP and NMC insecticides now to prevent continued male reproductive harm. https://doi.org/10.1289/EHP12678.
Topics: Humans; Male; Adult; Insecticides; Organophosphates; Semen; Carbamates; Spermatozoa
PubMed: 37966213
DOI: 10.1289/EHP12678 -
Toxics Oct 2023Organophosphorus compounds (OPs) have applications in agriculture (e.g., pesticides), industry (e.g., flame retardants), and chemical warfare (nerve agents). In high... (Review)
Review
Organophosphorus compounds (OPs) have applications in agriculture (e.g., pesticides), industry (e.g., flame retardants), and chemical warfare (nerve agents). In high doses or chronic exposure, they can be toxic or lethal. The primary mechanism, common among all OPs, that initiates their toxic effects is the inhibition of acetylcholinesterase. In acute OP exposure, the subsequent surge of acetylcholine in cholinergic synapses causes a peripheral cholinergic crisis and status epilepticus (SE), either of which can lead to death. If death is averted without effective seizure control, long-term brain damage ensues. This review describes the mechanisms by which elevated acetylcholine can cause respiratory failure and trigger SE; the role of the amygdala in seizure initiation; the role of M1 muscarinic receptors in the early stages of SE; the neurotoxic pathways activated by SE (excitotoxicity/Ca overload/oxidative stress, neuroinflammation); and neurotoxic mechanisms linked to low-dose, chronic exposure (Ca dyshomeostasis/oxidative stress, inflammation), which do not depend on SE and do not necessarily involve acetylcholinesterase inhibition. The evidence so far indicates that brain damage from acute OP exposure is a direct result of SE, while the neurotoxic mechanisms activated by low-dose chronic exposure are independent of SE and may not be associated with acetylcholinesterase inhibition.
PubMed: 37888716
DOI: 10.3390/toxics11100866 -
Cell Death & Disease Sep 2023Intracellular Ca signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca is intracellular BAPTA (BAPTA),...
Intracellular Ca signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca is intracellular BAPTA (BAPTA), usually introduced into cells as a membrane-permeant acetoxymethyl ester (BAPTA-AM). Previously, we demonstrated that BAPTA enhanced apoptosis induced by venetoclax, a BCL-2 antagonist, in diffuse large B-cell lymphoma (DLBCL). This finding implied a novel interplay between intracellular Ca signaling and anti-apoptotic BCL-2 function. Hence, we set out to identify the underlying mechanisms by which BAPTA enhances cell death in B-cell cancers. In this study, we discovered that BAPTA alone induced apoptosis in hematological cancer cell lines that were highly sensitive to S63845, an MCL-1 antagonist. BAPTA provoked a rapid decline in MCL-1-protein levels by inhibiting mTORC1-driven Mcl-1 translation. These events were not a consequence of cell death, as BAX/BAK-deficient cancer cells exhibited similar downregulation of mTORC1 activity and MCL-1-protein levels. Next, we investigated how BAPTA diminished mTORC1 activity and identified its ability to impair glycolysis by directly inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) activity, a previously unknown effect of BAPTA. Notably, these effects were also induced by a BAPTA analog with low affinity for Ca. Consequently, our findings uncover PFKFB3 inhibition as an Ca-independent mechanism through which BAPTA impairs cellular metabolism and ultimately compromises the survival of MCL-1-dependent cancer cells. These findings hold two important implications. Firstly, the direct inhibition of PFKFB3 emerges as a key regulator of mTORC1 activity and a promising target in MCL-1-dependent cancers. Secondly, cellular effects caused by BAPTA are not necessarily related to Ca signaling. Our data support the need for a reassessment of the role of Ca in cellular processes when findings were based on the use of BAPTA.
Topics: Myeloid Cell Leukemia Sequence 1 Protein; Phosphoric Monoester Hydrolases; Egtazic Acid; Phosphofructokinase-2; Neoplasms
PubMed: 37684238
DOI: 10.1038/s41419-023-06120-4