Detoxification Pathways Research Articles

Oxidative Stress in Genetic Cataract Formation

Background: Cataracts are the leading cause of blindness worldwide, and age-related cataracts are the result of environmental insults that largely lead to oxidative stress imposed on a genetic background that determines susceptibility to these stresses. Methods: A comprehensive literature review was performed to identify GWAS, targeted association studies, and TWAS that identified genes associated with age-related cataract. Additional genes associated with age-related cataracts were identified through the CAT-MAP online database. Pathway analysis was performed using Qiagen Ingenuity Pathway Analysis and pathways related to oxidative stress were analyzed using the same program. Results: A large number of genes have been identified as causes of both Mendelian and complex cataracts. Of these, 10 genes related to oxidative stress were identified, and all were associated with age-related cataracts. These genes fall into seven canonical pathways primarily related to glutathione metabolism and other pathways related to detoxifying reactive oxygen species. Conclusions: While a relatively small number of antioxidant related genes were identified as being associated with cataracts, they allow the identification of redox pathways important for lens metabolism and homeostasis. These are largely related to glutathione and its metabolism, other pathways for detoxification of reactive oxygen species, and the transcriptional systems that control their expression.

Identification and characterization of a novel formaldehyde dehydrogenase in Bacillus subtilis.

Formaldehyde is a key metabolite in methanol assimilation for many methylotrophic microorganisms, and at the same time, it is toxic to all living cells, which means its intracellular concentrations must be tightly controlled. An in-depth understanding of methanol detoxification systems in industrially relevant microorganisms is a prerequisite for the introduction of methanol utilization pathways into their metabolism (synthetic methylotrophy). Bacillus subtilis, an industrial workhorse conventionally used for the production of enzymes, is known to possess two formaldehyde detoxification pathways. Here, we identify a novel formaldehyde dehydrogenase in this bacterium as a path towards creating innovative prospect strategies for strain engineering towards synthetic methylotrophy.

Hepatic toxicity assessment in HIV’s interaction with reverse transcriptase and integrase strand transfer inhibitors at a military hospital, southsouth Nigeria

IntroductionThe use of anti-retroviral therapy (ART) has made HIV a manageable condition, but there are risks associated with medications like reverse transcriptase inhibitors (RTIs) and integrase strand transfer inhibitors (INSTIs), such as liver and renal toxicity. It is essential to understand these risks for effective treatment and case management. Investigating liver toxicity related to RTIs and INSTIs in Nigeria is crucial for optimizing HIV treatment. This study aimed to assess the impact of tenofovir lamivudine dolutegravir (TLD) on the liver function of HIV patients at Nigerian Navy Hospital (NNH)-Warri.MethodsThe liver function of 170 participants was assessed, with 120 on ART and the remainder being HIV-negative attendees at NNH-Warri. The study used a cross-sectional design and selected participants through random sampling. We collected data using a semi-structured questionnaire. Blood samples were taken through venipuncture and stored at – 20 °C before analysis. Ethical approval was obtained, and data analysis was conducted using SPSS Statistical Software Version 23, with significance set at p < 0.05.ResultsThe study found significant differences in AST, TP, Alb, and GST levels between HIV-positive subjects receiving TLD and HIV-negative individuals. HIV-positive subjects had lower AST and Alb levels but higher TP and GST levels. Further analysis revealed correlations between age, gender, and liver enzymes, highlighting the complex relationship between HIV, liver function, and treatment outcomes.ConclusionThe study suggests that decreased AST levels may have a protective effect, while ALT activity had minimal impact. Changes in TP, Alb, and GSTs emphasize the importance of monitoring hepatic synthetic function and detoxification pathways in HIV patients taking TLD.

Comparison of urinary 3-hydroxybenzo(a)Pyrene (3-OHBaP) and trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)Pyrene (TetraolBaP) as biomarkers of exposure to carcinogenic BaP

IntroductionBiomonitoring of exposure to carcinogenic Benzo(a)Pyrene is generally based on measurement of urinary 3-hydroxybenzo(a)pyrene (3-OHBaP), but its analysis is complex and only reflects the BaP detoxification pathway. TetraolBaP, another BaP metabolite resulting from the metabolic activation pathway, is now available but has not yet been studied in occupational settings or compared with 3-OHBaP. MethodsBiomonitoring was carried out on 118 subjects working in the aluminium smelting industry. 3 urine samples were collected from each subject at the beginning and end of the working week. Pyrene metabolite (1-hydroxypyrene) and the two BaP biomarkers (3-OHBaP and TetraolBaP) were analysed using LC-Fluorescence and GC-NCI-MS-MS. ResultsThe workers studied were found to be highly exposed, with 1-OHP and 3-OHBaP frequently exceeding maximum recommended values in occupational settings. Maximum concentrations were measured at end of shift+16h for all biomarkers, highlighting dermal exposure and/or temporary storage. Correlations were strong between 1-OHP and 3-OHBaP (r = 0.68–0.75) as well as between 3-OHBaP and TetraolBaP (r = 0.67–0.78), and moderate between 1-OHP and TetraolBaP (r = 0.59–0.76). While TetraolBaP levels were higher at low PAH exposures, TetraolBaP increased much more slowly at high exposures, indicating progressive saturation of the bioactivation pathway. The [3-OHBaP]/[TetraolBaP] ratio was found to be significantly lower in chronically exposed workers. Urinary TetraolBaP levels corresponding to 1-OHP (2.5 μg/L or 1 μmol/mol creatinine) or 3-OHBaP (0.4 nmol/mol creatinine) guidance values were found to range between 0.84 and 0.95 nmol/mol creatinine. ConclusionsTetraolBaP, resulting from carcinogenic BaP's metabolic activation pathway, was shown to be a diagnostically specific and sensitive biomarker for determining subjects' toxic internal exposure to PAHs in different contexts (occupational settings, environment) and assessing health risks.

Elevated temperature increases the susceptibility of D. magna to environmental mixtures of carbamazepine, tramadol and citalopram

The joint risks assessment of thermal stress and rising loads of pharmaceuticals (PhACs) in surface waters is a relevant topic in aquatic ecotoxicology. This study investigated the relevance of increased water temperature to alter the acute toxicity of environmentally relevant carbamazepine (CBZ), citalopram (CIT) and tramadol (TRA) concentrations as mixtures (ECs) and delayed outcomes in Daphnia magna. Responses of detoxification and antioxidant pathways in premature daphnids post an acute 24 h (pulsed) exposure to the PhACs mixtures and delayed responses as the reproductive output over 14 days recovery were investigated under 21- and 26 °C incubation. Biphasic modulation in glutathione S-transferase (GST) activity and significant inhibition of superoxide dismutase (SOD) activity were observed in both thermal regimes with significant shift in effective thresholds from 10-fold ECs at 21 °C to ECs at 26 °C incubation. Significant induction in catalase (CAT) activity and oxidative stress development were recorded at elevated temperatures from the 10-fold ECs dose onward. Pulsed exposures at 26 °C also led to significant decrease in the reproduction of daphnids above the 10-fold ECs of PhACs. The Integrated Biomarker Response scoring (IBRv2) approach outlined a 1.8-fold increase in alterations of daphnids exposed to 100-fold ECs of PhACs at 26 °C.

Assessing the chronic toxicity of climbazole to Daphnia magna: Physiological, biochemical, molecular, and reproductive perspectives

The widespread use of climbazole (CBZ) has led to its increased presence in aquatic environments, potentially threatening freshwater ecosystems. However, evidence regarding the harmful effects of CBZ on aquatic organisms remains limited. In this study, Daphnia magna was exposed to CBZ at concentrations of 0, 0.2, 20, and 200 μg/L for 21 days to evaluate its chronic toxicity through assessment of life-history traits, physiological parameters, biochemical analyses, and gene expression. The results indicated that CBZ exposure delayed the days to the first brood, reduced the frequency of molting per adult, decreased the offspring number at first brood, diminished the body length, and decreased both the total number of broods per female and the total number of offspring per female. Additionally, CBZ inhibited the swimming speed, filtration rate, and ingestion rate. Moreover, CBZ altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while increasing malondialdehyde (MDA) levels. Gene expression analysis revealed varied responses in mRNA levels related to metabolic detoxification (cyp360a8, gst, and p-gp), digestive enzymes (α-amylase, α-esterase, and trypsin), energy (ak), oxygen transport (dhb), and reproduction (nvd, cyp314, ecr, vtg, and jhe) following CBZ exposure. These results indicate that the presence of CBZ in aquatic environments can induce toxicity by altering energy acquisition, supply, and metabolism; impairing metabolic detoxification pathways; eliciting oxidative stress; and causing reproductive toxicity in D. magna.

Metatranscriptomics provides an in-depth perspective on the resistance and detoxification of anammox bacteria to dissolved oxygen in a pilot CANON process

In the completely autotrophic nitrogen removal over nitrite (CANON) process, the conflicting oxygen requirements of anammox and ammonium-oxidizing bacteria often lead to retardation in anammox activity. However, our study achieved stable nitrogen removal with a maximum capacity of 1096 g-N/m3/d in a 20 m3 CANON reactor under long-term intensive aeration. The anammox bacteria unusually distributed in the outer layer of the biofilm and demonstrated remarkable oxygen tolerance. Their activity only declined by 18.5 % under 2.0 mg/L of dissolved oxygen. When anammox bacteria encountered oxygen exposure, they adopted some strategies. Metatranscriptomics revealed that Candidatus Kuenenia, the dominant anammox species in our system, downregulated its gene expressions involved in carbon metabolism and oxidative phosphorylation. This may reduce electron leakage that combines with O2, thereby minimizing the generation of reactive oxygen species (ROS). By contrast, the secretion of extracellular proteins and conversion of O2·− were upregulated to eliminate ROS promptly. This behavior endowed Ca. Kuenenia with a unique oxygen detoxification pathway: O2·− were initially converted to H2O2 by superoxide dismutase SOD2 and superoxide reductase dfx (major role), followed by reduction to H2O via non-heme chloroperoxidase cpo (a newly recognized mechanism in the oxygen detoxification of anammox) and catalase katE. These results expanded the current knowledge of anammox alleviating oxidative stress.

Isothiocyanate-Rich Moringa Seed Extract Activates SKN-1/Nrf2 Pathway in Caenorhabditis elegans.

Moringa oleifera is a tropical tree that has its leaves, fruits, and seeds used as medicine and food. A standardized hydroalcoholic moringa seed extract (MSE) contains up to 40% of an isothiocyanate (MIC-1; moringin), a phytochemical known to have antioxidant and anti-inflammatory properties. Animal studies suggest that MSE may help with diseases, such as edema, colitis, obesity, and diabetes. In vitro studies have shown that MIC-1 activates the Nrf2 pathway, involved in detoxification and antioxidant pathways. To broaden the understanding of the molecular pathways regulated by MSE, we hypothesized that MSE improves the health span in Caenorhabditis elegans by activating the Nrf2 homolog (SKN-1). Our whole RNA-seq data showed that MSE at 0.1 mg/mL (100 µM MIC-1) regulated the expression of a total of 1555 genes, including genes related to C. elegans cuticle, molting cycle, and glutathione metabolism. MSE upregulated several glutathione S transferases (GST), involved in the detoxification of xenobiotics, and other SKN-1 downstream targets. MSE and MIC-1 upregulate skn-1 expression and induce SKN-1 nuclear translocation, suggesting that they activate the SKN-1/Nrf2 pathway. Moreover, the regulation of glutathione metabolism is likely dependent on the SKN-1 pathway, as the gst-4 upregulation by MSE was inhibited in skn-1 knockout mutant. However, MSE decreased survivability and delayed growth rate, while purified MIC-1 increased the lifespan of C. elegans. This study shows that MIC-1 is responsible for SKN-1/Nrf2 activation by MSE; however, components other than MIC-1 within MSE likely cause detrimental effects in C. elegans.

Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells.

Exposure to military burn pit smoke during deployment is associated with different respiratory and non-respiratory diseases. However, information linking smoke exposure to human pulmonary health is lacking. This study examined the effects of simulated burn pit smoke condensates on human airway epithelial cells (HAECs) from twelve donors (smokers/non-smokers, biological female/male) cultured at an air-liquid interface and exposed to condensates from three simulated burn pit waste materials (cardboard, plywood, and plastic) incinerated at two combustion conditions: smoldering and flaming. Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay. Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs. This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. Future studies are needed to further characterize how sex and smoking status affect deployment-related diseases.

The role of carbon textile surface functionalities in reactive adsorption of vapor and liquid 2-chloroethyl ethyl sulfide: Evaluating interactions at the interface

A carbon textile (CT) was chemically modified to increase its surface activity and promote the adsorption and degradation of 2-chloroethyl ethyl sulfide (CEES) - a surrogate for mustard gas. CT was initially subjected to oxidation (CTO), and then heated under ammonia (CTON) or hydrogen sulfide (CTOS) atmosphere to incorporate nitrogen or sulfur functionalities, respectively. Detoxification experiments were performed in closed vials using either vapor or liquid forms of CEES. The maximum vapor weight uptakes on CT, CTO, CTOS, and CTON were 399, 372, 434, and 489 mg/g, respectively. All textiles were able to prevent the vaporization of CEES liquid droplets. Although similar reaction products were detected in both vapor and liquid systems, the marked differences in the extent of CEES chemical transformation on the surfaces of the textiles indicate distinct detoxification pathways influenced by surface chemistry. Even though the heterogeneous surface of CTO, enriched with oxygen surface groups, facilitated various reactions, hydrolysis was the predominant pathway. The thermal treatment, regardless of the atmosphere, reduced the oxygen content, decreasing the extent of hydrolysis. However, incorporating basic surface groups such as pyridines, amines, or weak acids such as thiols promoted dehydrohalogenation as the main detoxification pathway on these samples.

Ecotoxicological insights into the effects of triflumezopyrim on P. fuscipes fitness, detoxification pathways, and gene expression

The primary objective was to evaluate the toxicity of triflumezopyrim (TFP) on P. fuscipes larvae and adults at lethal and sublethal levels through topical application. Sublethal effects were assessed by examining developmental period, fecundity, life-table parameters, and fitness parameters. Enzymatic and transcriptional analyses were conducted to determine the impact of TFP on P. fuscipes physiology and gene expression. The LC50, LC30, and LC10 of TFP against P. fuscipes larvae and adults were lower than the field-recommended dose (48.75 mg a.i. L−1), indicating direct toxicity and sublethal effects during immature stages. Exposure to LC30 of TFP extended developmental periods for 2nd-instar larvae and pupae, reduced oviposition, larval predation efficiency, and body weight in both sexes. Sublethal concentrations affected antioxidant, detoxification, and energy reservoir enzymes significantly. Transcriptional analysis revealed impacts on insecticide detoxification, resistance, and stress-related genes. KEGG analysis showed glycerolipid metabolism is the most regulated pathway, and UGT2B10 regulated several detoxification-related pathways under TFP stress. These findings prompt reconsideration of the role of TFP in paddy field IPM due to its adverse effects on P. fuscipes, emphasizing the importance of assessing its ecological impacts before widespread application in agricultural practices.

Comparing alpha-synuclein-interactomes between multiple systems atrophy and Parkinson's disease reveals unique and shared pathological features.

Primary synucleinopathies, such as Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are neurodegenerative disorders with some shared clinical and pathological features. Aggregates of alpha-synuclein (αsyn) phosphorylated at serine 129 (PSER129) are the hallmark of synucleinopathies, which for PD/DLB are found predominantly in neurons (Neuronal cytoplasmic inclusions "NCIs"), but for MSA, aggregates are primarily found in oligodendroglia (Glial cytoplasmic inclusions "GCIs"). It remains unclear if the distinct pathological presentation of PD/DLB and MSA are manifestations of distinct or shared pathological processes. We hypothesize that the distinct synucleinopathies MSA and PD/DLB share common molecular features. Using the in-situ proximity labeling technique biotinylation by antibody recognition (BAR), we compare aggregated αsyn-interactomes (BAR-PSER129) and total αsyn-interactomes (BAR-MJFR1) between MSA (n=5) and PD/DLB (n=10) in forebrain and midbrain structures. For BAR-PSER129 and BAR-MJFR1 captures, αsyn was the most significantly enriched protein in PD/DLB and MSA. In PD/DLB, BAR-PSER129 identified 194 αsyn-aggregate-interacting proteins, while BAR-MJFR1 identified 245 αsyn interacting proteins. In contrast, in the MSA brain, only 38 and 175 proteins were identified for each capture, respectively. When comparing MSA and PD/DLB, a high overlap (59.5%) was observed between BAR-MJFR1 captured proteins, whereas less overlap (14.4%) was observed for BAR-PSER129. Direct comparison between MSA and PD/DLB revealed 79 PD/DLB-associated proteins and only three MSA-associated proteins (CBR1, CRYAB, and GFAP). Pathway enrichment analysis revealed PD/DLB interactions were dominated by vesicle/SNARE-associated pathways, in contrast to MSA, which strongly enriched for metabolic/catabolic, iron, and cellular oxidant detoxification pathways. A subnetwork of cytosolic antioxidant enzymes called peroxiredoxins drove cellular detoxification pathways in MSA. A common network of 26 proteins, including neuronal-specific proteins (e.g., SNYGR3) with HSPA8 at the core, was shared between MSA and DLB/PD. Extracellular exosome pathways were universally enriched regardless of disease or BAR target protein. Synucleinopathies have divergent and convergent αsyn-aggregate interactions, indicating unique and shared pathogenic mechanisms. MSA uniquely involves oxidant detoxification processes in glial cells, while vesicular processes in neurons dominate PD/DLB. Shared interactions, specifically SNYGR3 (i.e., a neuronal protein), between MSA and PD/DLB suggest neuronal axons origin for both diseases. In conclusion, we provide αsyn aggregates protein interaction maps for two distinct synucleinopathies.

Investigating the role of the ROS/CncC-xenobiotics signaling pathway in the response to Fenpropathrin in Cyprinus carpio lymphocytes: Involving lipid peroxidation and Fe2+ metabolism imbalance

Fenpropathrin (FPT) is a synthetic pyrethroid insecticide, the persistence and accumulation in water of which could cause harmful effects on vulnerable groups like aquatic creatures, particularly posing significant risks to fish immune systems. This study aimed to investigate how environmentally relevant FPT concentrations (10–1000 μ/M) affect lipid peroxidation and Fe2+ metabolism in Cyprinus carpio head kidney lymphocytes, and its relationship with oxidative stress and immunotoxicity. Firstly, CCK-8 results demonstrated that FPT caused a significant increase in lymphocyte death. Secondly, lymphocytes exposed to FPT could lead ferroptosis in lymphocytes, accompanied by evidence of the Fe2+ transporter imbalance, lipid peroxidation, Fe2+ accumulation and ferroptosis related protein increment. Thirdly, we found that FPT esposure leads to a decrease in ATP, mitochondrial DNA and NADPH/NADP+ levels, and the mRNA associated with mitochondrial function-related genes (Fis1, Drp1, and OPA1) in lymphocytes. Additionally, FPT induced the increased the levels of inflammatory genes (TNF-α, IFN-γ, and IL-6) in head kidney lymphocytes. Importantly, exposure to FPT induced oxidative stress to produce intracellular ROS, disrupting the function of the CncC signaling pathway and expression disorder of xenobiotics detoxification (CYP 450 family) genes. Notably, Treatment with NAC (a ROS inhibitor, 5 μM) demonstrated that inhibiting ROS alleviated FPT-induced lymphocyte ferroptosis and inflammatory response via the ROS/CncC-xenobiotics signaling pathway. These findings not only introduces a novel approach to investigating the immunotoxicity of FPT but also offers critical insights into mitigating the adverse effects of FPT on aquatic animal health.

The aryl hydrocarbon receptor in environmentally induced cervical cancer: A Narrative review

The aryl hydrocarbon receptor (AhR) plays a crucial role in cellular responses to various environmental pollutants, including several known carcinogens. As a ligand-activated transcription factor, AhR activation modulates the expression of genes involved in critical cellular processes, including detoxification pathways, cell proliferation and differentiation, and immune system regulation. The AhR exhibits pleiotropic effects under normal physiological conditions, contributing to the development and function of various organ systems. AhR activity is important in angiogenesis, cardiomyocyte differentiation, oocyte maturation, oculomotor nerve formation, and hematopoietic stem cell maintenance. Additionally, AhR plays a role in regulating immune cell differentiation and function, maintaining the integrity of the intestinal epithelium and its associated immune system, and mediating UVB-induced DNA damage repair responses in the skin. It acts as a critical environmental sensor, mediating cellular responses to various exogenous ligands. Importantly, activation or inhibition of AhR affects distinct signaling pathways depending on the specific ligand and cellular context. Ligands for the AhR are divided into exogenous or endogenous and have agonistic or antagonistic activity. Recently, the AhR role was determined in cancer development. It can exert both tumor-promoting and tumor-suppressive effects depending on factors such as the specific ligand, cell type, and tissue microenvironment. Emerging evidence suggests that AhR may represent a promising target for immunotherapy and serve as a potential biomarker for cervical cancer. AhR interacts with apoptotic pathway, immune checkpoint system, steroid hormones, and immune cell regulation process in cervical cancer. Despite its potential significance, the precise role of AhR in cervical cancer development and progression is still unknown. In this review, we describe significant roles of AhR in gynecological cancers; e.g., in cervical cancer.

Microbial strategies for lead remediation in agricultural soils and wastewater: mechanisms, applications, and future directions.

High lead (Pb) levels in agricultural soil and wastewater threaten ecosystems and organism health. Microbial remediation is a cost-effective, efficient, and eco-friendly alternative to traditional physical or chemical methods for Pb remediation. Previous research indicates that micro-organisms employ various strategies to combat Pb pollution, including biosorption, bioprecipitation, biomineralization, and bioaccumulation. This study delves into recent advancements in Pb-remediation techniques utilizing bacteria, fungi, and microalgae, elucidating their detoxification pathways and the factors that influence Pb removal through specific case studies. It investigates how bacteria immobilize Pb by generating nanoparticles that convert dissolved lead (Pb-II) into less harmful forms to mitigate its adverse impacts. Furthermore, the current review explores the molecular-level mechanisms and genetic engineering techniques through which microbes develop resistance to Pb. We outline the challenges and potential avenues for research in microbial remediation of Pb-polluted habitats, exploring the interplay between Pb and micro-organisms and their potential in Pb removal.

Fungi from Antarctic marine sediment: characterization and assessment for textile dye decolorization and detoxification.

Cold-adapted microorganisms can produce enzymes with activity at low and mild temperatures, which can be applied to environmental biotechnology. This study aimed to characterize 20 Antarctic fungi to identify their genus (ITS rDNA marker) and growth temperatures and evaluate their ability to decolorize and detoxify the textile dye indigo carmine (IC). An individual screening was performed to assess the decolorization and detoxification of IC by the isolates, as well as in consortia with other fungi. The isolates were affiliated with seven ascomycete genera: Aspergillus (n = 4), Cosmospora (n = 2), Leuconeurospora (n = 2), Penicillium (n = 3), Pseudogymnoascus (n = 6), Thelebolus (n = 2), and Trichoderma (n = 1). The two isolates from the genus Leuconeurospora were characterized as psychrophilic, while the others were psychrotolerant. The Penicillium isolates were able to decolorize between 60 and 82% of IC. The isolates identified as Pseudogymnoascus showed the best detoxification capacity, with results varying from 49 to 74%. The consortium using only Antarctic ascomycetes (C1) showed 45% of decolorization, while the consortia with the addition of basidiomycetes (C1 + Peniophora and C1 + Pholiota) showed 40% and 50%, respectively. The consortia C1 with the addition of the basidiomycetes presented a lower toxicity after the treatments. In addition, a higher fungal biomass was produced in the presence of dye when compared with the experiment without the dye, which can be indicative of dye metabolization. The results highlight the potential of marine-derived Antarctic fungi in the process of textile dye degradation. The findings encourage further studies to elucidate the degradation and detoxification pathways of the dye IC by these fungal isolates.

17α-Ethynylestradiol and Levonorgestrel Exposure of Rainbow Trout RTL-W1 Cells at 18 °C and 21 °C Mainly Reveals Thermal Tolerance, Absence of Estrogenic Effects, and Progestin-Induced Upregulation of Detoxification Genes.

Fish are exposed to increased water temperatures and aquatic pollutants, including endocrine-disrupting compounds (EDCs). Although each stressor can disturb fish liver metabolism independently, combined effects may exist. To unveil the molecular mechanisms behind the effects of EDCs and temperature, fish liver cell lines are potential models needing better characterisation. Accordingly, we exposed the rainbow trout RTL-W1 cells (72 h), at 18 °C and 21 °C, to ethynylestradiol (EE2), levonorgestrel (LNG), and a mixture of both hormones (MIX) at 10 µM. The gene expression of a selection of targets related to detoxification (CYP1A, CYP3A27, GST, UGT, CAT, and MRP2), estrogen exposure (ERα, VtgA), lipid metabolism (FAS, FABP1, FATP1), and temperature stress (HSP70b) was analysed by RT-qPCR. GST expression was higher after LNG exposure at 21 °C than at 18 °C. LNG further enhanced the expression of CAT, while both LNG and MIX increased the expressions of CYP3A27 and MRP2. In contrast, FAS expression only increased in MIX, compared to the control. ERα, VtgA, UGT, CYP1A, HSP70b, FABP1, and FATP1 expressions were not influenced by the temperature or the tested EDCs. The RTL-W1 model was unresponsive to EE2 alone, sensitive to LNG (in detoxification pathway genes), and mainly insensitive to the temperature range but had the potential to unveil specific interactions.

New tools for effective production and long-term stabilization of microcystinase (MlrA) - A biotechnological perspective towards hepatotoxic microcystins remediation

Microcystinase (MlrA) is the most specific catalyst and the most efficient enzyme of known microcystins (MCs) detoxification pathways. Very recently, direct MlrA application has effectively degraded MCs within industrial processes, demonstrating MlrA application for sustainable in situ MCs remediation. Heterologous MlrA expression in cyanobacteria offers a unique opportunity, linking harmful MCs remediation with emerging cyanobacterial biotechnologies. Here, we first generate a novel Synechocystis sp. PCC 6803 (6803) using non-native trc promoter for MlrA expression. Whole-cell MlrA activity was comparable to previously described expression via native 6803 PcpcB560 promoter, while cellular extracts of the new strain showed significantly higher MlrA yields (2–15 times, depending on the age of the cultures). Furthermore, efficiency of MlrA production under multiple photoautotrophic cultivation conditions varied, but was not improved by Na2CO3 supplementation nor under increased light, indicating the need to explore new photoautotrophic chassis for higher MlrA productivity.Methods for MlrA stabilization are critical for industrial development, thus lyophilization of MlrA-enriched cellular extracts was explored. Recovered MlrA activity was not statistically different from initial MlrA activity following storage of lyophilized extracts at −20 °C for 20 weeks. In contrast, storage at 20 °C and storage of aqueous lysates at 4 °C resulted in progressive MlrA activity loss. Such stabilized lyophilizate may offer a checkpoint for further optimization of upstream processes (production), while expanding potential for downstream investigations (application), contributing simultaneously to novel MlrA-based MCs remediation approaches and to cyanobacterial biotechnology.

Photodynamic therapy on mRNA levels in bacteria.

Antimicrobial photodynamic therapy (aPDT) has shown efficacy in inactivating different bacterial species by photosensitizer-induced free radical production. Despite aPDT is considered unable to cause resistant strains, enzymatic pathways for detoxification of reactive oxygen species and transmembrane photosensitizer efflux systems could cause resistance to aPDT. Resistance mechanisms can be evaluated by measurement of mRNA from by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Thus, the aim of this study was to access the mRNA level data obtained by RT-qPCR in bacterial cells submitted to photodynamic therapy. Studies performed on mRNA levels in bacteria after PDT were assessed on MEDLINE/Pubmed. The mRNA levels from genes related to various functions have been successfully evaluated in both Gram-positive and -negative bacteria after aPDT by RT-qPCR. Such an approach has improved the understanding of aPDT-induced effects, and reinforced the effectiveness of aPDT on bacteria, which can cause infections in different human tissues.

Transgenerational and parental impacts of acrylamide exposure on Caenorhabditis elegans: Physiological, behavioral, and genetic mechanisms

Acrylamide is pervasive, and its exposure poses numerous health risks. This study examines both the direct and transgenerational effects of acrylamide toxicity in Caenorhabditis elegans, focusing on physiological and behavioral parameters. Parental exposure to acrylamide compromised several aspects of nematode health, including lifespan, reproductive capacity, body dimensions, and motor and sensory functions. Notably, while exposure to low concentrations of acrylamide did not alter the physiological traits of the offspring—except for their learning and memory—these findings suggest a possible adaptive response to low-level exposure that could be inherited by subsequent generations. Furthermore, continued acrylamide exposure in the offspring intensified both physiological and perceptual toxicity. Detailed analysis revealed dose-dependent alterations in acrylamide's detoxification and metabolic pathways. In particular, it inhibits the gene gst-4, which encodes a crucial enzyme in detoxification, mitigates DNA damage induced by acrylamide, and highlights a potential therapeutic target to reduce its deleterious effects.