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The widespread use of toothpaste containing various chemical formulations has raised concern regarding their potential impact on aquatic ecosystems. This research examines the molecular toxicity of popular toothpaste brands on post-juveniles of Clarias gariepinus from a commercial fish farm in Akure, Ondo State, Nigeria. Specifically assessing the impact of these toothpaste brands on the mRNA expression levels of the heat shock protein (HSP70), interleukin (IL-1β), melatonin receptors (MEL1C), and growth hormone in comparison to a control group. The results revealed a significant upregulation of HSP70, IL-1β, and MEL1C genes in the exposed group, indicating a potential stress response and immune system activation. Intriguingly, the growth hormone mRNA expression remained unaffected in the treated group compared to the control. These findings underscore the need for further exploration into the potential molecular consequences of common toothpaste ingredients on aquatic organisms, raising important questions about environmental safety and consumer product development. [ABSTRACT FROM AUTHOR]

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

The widespread use of toothpaste containing various chemical formulations has raised concern regarding their potential impact on aquatic ecosystems. This research examines the molecular toxicity of popular toothpaste brands on post-juveniles of Clarias gariepinus from a commercial fish farm in Akure, Ondo State, Nigeria. Specifically assessing the impact of these toothpaste brands on the mRNA expression levels of the heat shock protein (HSP70), interleukin (IL-1β), melatonin receptors (MEL1C), and growth hormone in comparison to a control group. The results revealed a significant upregulation of HSP70, IL-1β, and MEL1C genes in the exposed group, indicating a potential stress response and immune system activation. Intriguingly, the growth hormone mRNA expression remained unaffected in the treated group compared to the control. These findings underscore the need for further exploration into the potential molecular consequences of common toothpaste ingredients on aquatic organisms, raising important questions about environmental safety and consumer product development.

Triclosan (TCS), a commonly used antibacterial preservative, has been demonstrated to have high toxicological potential and adversely affects the water bodies. Since algae are one of the most significant primary producers on the planet, understanding the toxicological processes of TCS is critical for determining its risk in aquatic ecosystems and managing the water environment. The physiological and transcriptome changes in Euglena gracilis were studied in this study after 7 days of TCS treatment. A distinct inhibition ratio for the photosynthetic pigment content in E. gracilis was observed from 2.64% to 37.42% at 0.3–1.2 mg/L, with TCS inhibiting photosynthesis and growth of the algae by up to 38.62%. Superoxide dismutase and glutathione reductase significantly changed after exposure to TCS, compared to the control, indicating that the cellular antioxidant defense responses were induced. Based on transcriptomics, the differentially expressed genes were mainly enriched in biological processes involved in metabolism pathways and microbial metabolism in diverse environments. Integrating transcriptomics and biochemical indicators found that changed reactive oxygen species and antioxidant enzyme activities stimulating algal cell damage and the inhibition of metabolic pathways controlled by the down-regulation of differentially expressed genes were the main toxic mechanisms of TCS exposure to E. gracilis. These findings establish the groundwork for future research into the molecular toxicity to microalgae induced by aquatic pollutants, as well as provide fundamental data and recommendations for TCS ecological risk assessment. [ABSTRACT FROM AUTHOR]

Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of PGM2, a phosphoglucomutase that influences sugar metabolism in yeast. In the presence of galactose, when yeast cells are challenged by LiCl, the phosphoglucomutase activity of PGM2p is decreased, causing an increase in the concentration of toxic galactose metabolism intermediates that result in cell sensitivity. Here, we report that the null yeast mutant strains DBP7∆ and YRF1-6∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that DBP7 and YRF1-6 modulate the translational level of PGM2 mRNA, and the observed alteration in translation seems to be associated with the 5′-untranslated region (UTR) of PGM2 mRNA. Furthermore, we observe that DBP7 and YRF1-6 influence, to varying degrees, the translation of other mRNAs that carry different 5′-UTR secondary structures. [ABSTRACT FROM AUTHOR]

Triclosan (TCS), a commonly used antibacterial preservative, has been demonstrated to have high toxicological potential and adversely affects the water bodies. Since algae are one of the most significant primary producers on the planet, understanding the toxicological processes of TCS is critical for determining its risk in aquatic ecosystems and managing the water environment. The physiological and transcriptome changes in Euglena gracilis were studied in this study after 7 days of TCS treatment. A distinct inhibition ratio for the photosynthetic pigment content in E. gracilis was observed from 2.64% to 37.42% at 0.3–1.2 mg/L, with TCS inhibiting photosynthesis and growth of the algae by up to 38.62%. Superoxide dismutase and glutathione reductase significantly changed after exposure to TCS, compared to the control, indicating that the cellular antioxidant defense responses were induced. Based on transcriptomics, the differentially expressed genes were mainly enriched in biological processes involved in metabolism pathways and microbial metabolism in diverse environments. Integrating transcriptomics and biochemical indicators found that changed reactive oxygen species and antioxidant enzyme activities stimulating algal cell damage and the inhibition of metabolic pathways controlled by the down-regulation of differentially expressed genes were the main toxic mechanisms of TCS exposure to E. gracilis. These findings establish the groundwork for future research into the molecular toxicity to microalgae induced by aquatic pollutants, as well as provide fundamental data and recommendations for TCS ecological risk assessment.

Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of PGM2, a phosphoglucomutase that influences sugar metabolism in yeast. In the presence of galactose, when yeast cells are challenged by LiCl, the phosphoglucomutase activity of PGM2p is decreased, causing an increase in the concentration of toxic galactose metabolism intermediates that result in cell sensitivity. Here, we report that the null yeast mutant strains DBP7∆ and YRF1-6∆ exhibit increased LiCl sensitivity on galactose-containing media. Additionally, we demonstrate that DBP7 and YRF1-6 modulate the translational level of PGM2 mRNA, and the observed alteration in translation seems to be associated with the 5′-untranslated region (UTR) of PGM2 mRNA. Furthermore, we observe that DBP7 and YRF1-6 influence, to varying degrees, the translation of other mRNAs that carry different 5′-UTR secondary structures.

The presence of N -nitroso compounds, particularly N -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products. [Display omitted] • The nitrosamines crisis in pharmaceuticals is discussed. • We delve into the toxicological implications and toxicity profiles of N -nitroso compounds. • We discussed root cause analysis, risk assessment, and mitigation strategies for nitrosamine impurities. • We highlighted GC and LC methods for detection and quantification of N -nitroso compounds in pharmaceuticals. • The emphasis is on developing nitrosamine-free pharmaceutical products to ensure regulatory compliance. [ABSTRACT FROM AUTHOR]

The presence of N -nitroso compounds, particularly N -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Targeted therapy has revolutionized the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) with specific genetic abnormalities. It is still being described as a new landmark therapeutic approach. The main purpose of the use of molecularly targeted drugs and immunotherapy in the treatment of ALL is to improve the treatment outcomes and reduce the doses of conventional chemotherapy, while maintaining the effectiveness of the therapy. Despite promising treatment results, there is limited clinical research on the effect of target cell therapy on the potential toxic events in children and adolescents. The recent development of highly specific molecular methods has led to an improvement in the identification of numerous unique expression profiles of acute lymphoblastic leukemia. The detection of specific genetic mutations determines patients’ risk groups, which allows for patient stratification and for an adjustment of the directed and personalized target therapies that are focused on particular molecular alteration. This review summarizes the knowledge concerning the toxicity of molecular-targeted drugs and immunotherapies applied in childhood ALL.

More and more composite nano-photocatalysts were developed by doping, modifying and coupling, which expanded its application but resulted in pollution due to the unrecyclability. Composite photocatalyst TiO 2 /WO 3 /GO, as a model, was evaluated by exploring the molecular mechanism of TiO 2 /WO 3 /GO-induced activity changes of catalase (CAT) and superoxide dismutase (SOD). Results showed that TiO 2 /WO 3 /GO could lead to conformational and functional changes of CAT and SOD. The activity of both CAT and SOD increased depending on the exposure dose of TiO 2 /WO 3 /GO. The change skeleton structure and increase of α-helix content of CAT and SOD were certificated with UV–vis absorption and CD measurements. Intrinsic fluorescence of CAT and SOD were quenched by dynamic quenching. Micro-environment of amino acid residues of CAT and SOD became more hydrophilic, and the microenvironment of Trp residues was more vulnerable than Tyr residues with TiO 2 /WO 3 /GO exposure. In addition, inhibitory comparison between GO, TiO 2 , WO 3 and TiO 2 /WO 3 /GO was made, results showed that composite nano-photocatalyst exhibited different inhibitory compared to their parent nano-particles. [ABSTRACT FROM AUTHOR]

In the present survey, the plasma level of diazinon after acute exposure was measured by HPLC method at a time-course manner. In addition, the impact of diazinon on the expression of the key genes responsible for hepatocellular antioxidative defense, including PON1, GPx and CAT were investigated. The increase in oxidative damages in treated rats was determined by measuring LPO, protein carbonyl content and total antioxidant power in plasma. After administration of 85 mg/kg diazinon in ten groups of male Wistar rats at different time points between 0-24 hours, the activity of AChE enzyme was inhibited to about 77.94%. Significant increases in carbonyl groups and LPO after 0.75 and 1 hours were also observed while the plasma antioxidant power was significantly decreased. Despite the dramatic reduction of GPX and PON1 gene expression, CAT gene was significantly upregulated in mRNA level by 1.1 fold after 4 hours and 1.5-fold after 24 hours due to diazinon exposure, compared to control group. Furthermore, no significant changes in diazinon plasma levels were found after 4 hours in the treated rats. The limits of detection and quantification were 137.42 and 416.52 ng/mL, respectively. The average percentage recoveries from plasma were between 90.62% and 95.72%. In conclusion, acute exposure to diazinon increased oxidative stress markers in a time-dependent manner and the changes were consistent with effects on hepatic antioxidant gene expression pattern. The effect of diazinon even as a non-lethal dose was induced on the gene expression of antioxidant enzymes. The change in antioxidant defense system occurs prior to diazinon plasma peak time. These results provide biochemical and molecular evidence supporting potential acute toxicity of diazinon and is beneficial in the evaluation of acute toxicity of other organophosphorus pesticides as well. [ABSTRACT FROM AUTHOR]

The importance of evaluating the toxic effects associated with the use of reclaimed water has been increasing. The purpose of this research was to investigate the cytotoxicity and molecular toxicity of reclaimed water on the human embryonic kidney 293 (HEK293) cells. The culture medium was synthesized using the reclaimed water samples. Wastewater treatment plant influent (WTI) and effluent (WTE), containing micropollutants at the nanogram per liter level, decreased cell proliferation (93.4–98.9% and 91.5–96.6% of the control, respectively) and increased cell damage (103.6–117.5% and 100.7–109% of the control, respectively) at all exposure times, except for a decrease in cell damage observed after an 8-h exposure to WTE. Membrane bioreactor permeate (MBRP) increased cell proliferation (102.1–106.7% of the control) and decreased cell damage at 8 and 12 h (92.4 and 98.4% of the control, respectively), but slightly increased cell damage at 24 h and later time points (101.1–104.9% of the control). All three water samples induced cell apoptosis (120.9–123.4% of the control). They also affected the expression of cell-cycle regulatory proteins (p16 INK4a , p27 Kip1 , cyclin-dependent kinases 2 and 4, cyclin D1, and cyclin E) and apoptosis-related regulatory proteins ( p -JNK, Bcl-2, caspase-9, and caspase-3). In conclusion, all three water samples showed cytotoxicity and molecular toxicity in the HEK293 cells, and the results of the cell-cycle and apoptosis regulatory protein expression after WTI and WTE treatments were consistent with the results of the cytotoxicity. [ABSTRACT FROM AUTHOR]

Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism. Most studies show that antioxidants can attenuate oxidative stress and the consequent changes in liver function. However, few studies have examined the relationship between OP structures and the severity and mechanism of their action. We hope that future in vitro, in vivo, and clinical trials will answer the remaining questions about the mechanisms of OP hepatotoxicity and its management. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (nZnOs) released from popular sunscreens used during marine recreation apparently endanger corals; however, the known biological effects are very limited. Membrane lipids constitute the basic structural element to create cell a dynamic structure according to the circumstance. Nano-specific effects have been shown to mechanically perturb the physical state of the lipid membrane, and the cells accommodating the actions of nZnOs can be involved in the alteration of the membrane lipid composition. To gain insight into the effects of nanoparticles on coral, glycerophosphocholine (GPC) profiling of the coral Seriatopora caliendrum exposed to nZnOs was performed in this study. Increasing lyso-GPCs, docosapentaenoic acid-possessing GPCs and docosahexaenoic acid-possessing GPCs and decreasing arachidonic acid-possessing GPCs were the predominant changes responded to nZnO exposure in the coral. A backfilling of polyunsaturated plasmanylcholines was observed in the coral exposed to nZnO levels over a threshold. These changes can be logically interpreted as an accommodation to nZnOs-induced mechanical disturbances in the cellular membrane based on the biophysical properties of the lipids. Moreover, the coral demonstrated a difference in the changes in lipid profiles between intra-colonial functionally differentiated polyps, indicating an initial membrane composition-dependent response. Based on the physicochemical properties and physiological functions of these changed lipids, some chronic biological effects can be incubated once the coral receives long-term exposure to nZnOs. [ABSTRACT FROM AUTHOR]

Targeted therapy has revolutionized the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) with specific genetic abnormalities. It is still being described as a new landmark therapeutic approach. The main purpose of the use of molecularly targeted drugs and immunotherapy in the treatment of ALL is to improve the treatment outcomes and reduce the doses of conventional chemotherapy, while maintaining the effectiveness of the therapy. Despite promising treatment results, there is limited clinical research on the effect of target cell therapy on the potential toxic events in children and adolescents. The recent development of highly specific molecular methods has led to an improvement in the identification of numerous unique expression profiles of acute lymphoblastic leukemia. The detection of specific genetic mutations determines patients' risk groups, which allows for patient stratification and for an adjustment of the directed and personalized target therapies that are focused on particular molecular alteration. This review summarizes the knowledge concerning the toxicity of molecular-targeted drugs and immunotherapies applied in childhood ALL. [ABSTRACT FROM AUTHOR]

Oxygen-derived free radical damage is associated with the molecular toxicity of hemoglobin. Especially in thalassemia syndromes, this toxicity has a relationship with "free" alpha globin concentrations. This study of beta thalassemia trait blood samples from 39 individuals shows that the evaluation of methemoglobin is a sensitive method of indicating molecular toxicity and the superoxide dismutase concentration revealing the intensity of oxidative stress of this process.