Cellular Damage Research Articles

Unwinding the Threads of Mesoporous Silica Nanoparticles as Cutting-Edge for the Management of Inflammation: An Updated Review.

Inflammation serves as a protective response to combat cellular and tissue damage. There is currently a wide array of synthetic and traditional therapies available for the treatment of inflammatory diseases. However, it is necessary to create a drug delivery system based on nanotechnology that can improve the solubility, permeability, and bioavailability of current treatments. Mesoporous silica nanoparticles (MSNPs) are inorganic materials known for their organised porous interiors, high pore volumes, substantial surface area, exceptional selectivity, permeability, low refractive index, and customisable pore sizes. This review offers concise insights into the progression of the pathophysiology of inflammation, as well as the inducers, mediators, and effectors that are involved in the inflammatory pathway. This study focuses on the growing significance of MSNPs in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing applications. This review also presents the latest information on the crucial role of MSNPs in delivering herbal medicines for the treatment of inflammation. A comprehensive literature search was conducted for this aim, utilising the Google Scholar, PubMed, and ScienceDirect databases. A systematic review was undertaken utilising scholarly articles published in peer-reviewed journals from 2000 to 2024. The inflammatory mediators involved in the pathophysiology of inflammation include platelet-activating factor, lipoxygenase, cyclooxygenase, Interferon-α, interleukin-6, interleukin- 1β, matrix metalloproteinases, inducible nitric oxide synthase, nuclear factor-κB, prostaglandins, nitric oxide, and phospholipase A2. MSNPs have the potential to be used in the treatment of neuroinflammation, inflammatory bowel disease, arthritic inflammation, lung inflammation, and wound healing. The investigation of the MSNPs of plant-based compounds such as berberine, tetrahydrocannabinol, curcumin, and resveratrol has shown successful results in recent years for the purpose of managing inflammation. This review demonstrates that MSNPs have a strong potential to play a positive role in delivering synthetic and plant-based therapies for the treatment of inflammatory illnesses.

The role of NETosis in enhancing of atherosclerosis.

Activated neutrophils release neutrophil extracellular traps (NETs), complex structures composed of extracellular genetic material and proteins sourced from the nucleus, granules, and cytoplasm in response to pathogenic inflammatory conditions. These NETs play a crucial role in the host's innate immune defense against invasive infections. Notably, in conditions like atherosclerosis, these extracellular formations can also be elicited by inflammatory stimuli such as lipids, prothrombotic factors, platelet aggregation, or proinflammatory cytokines. NETs have been identified on the inner arterial walls in cardiovascular disease states. By promoting inflammation through NETosis-mediated cell adhesion processes and exerting cytotoxic effects leading to cellular dysfunction and tissue damage, NETs contribute to the pathogenesis of inflammatory conditions.

Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT’s efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments.

Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles as Natural Nanocarriers in the Treatment of Nephrotoxic Injury In Vitro.

This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects.

Butin Protects Keratinocytes From Particulate Matter 2.5 and Ultraviolet B-Mediated Damages.

Butin is a naturally occurring compound with a wide range of medicinal properties, including anti-inflammatory, anti-arthritic, and antioxidant properties. Particulate matter 2.5 (PM2.5) and ultraviolet B (UVB) radiation contribute to skin cell damage via the induction of oxidative stress. This study sought to assess the protective effects of butin against damage triggered by PM2.5 and UVB in human HaCaT keratinocytes. Assessments were performed to evaluate cell viability, apoptosis, and cellular component damage. Butin exhibited its protective ability via the inhibition of PM2.5-induced reactive oxygen species generation, lipid peroxidation, DNA damage, protein carbonylation, and mitochondrial damage. Butin reduced the PM2.5-induced c-Fos and phospho-c-Jun protein levels as well as mitogen-activated protein kinase. Furthermore, butin mitigated PM2.5- and UVB-induced apoptosis. Butin had the potential as a pharmaceutical candidate for treating skin damage caused by PM2.5 and UVB exposure.

Dual-Activated Photoacoustic Probe for Reliably Detecting Hydroxyl Radical in Ischemic Cardiovascular Disease in Mouse and Human Samples.

Cardiovascular disease (CVD) is a chronic disease characterized by the accumulation of lipids and fibrous tissue within the arterial walls, potentially leading to vascular obstruction and an increased risk of heart disease and stroke. Hydroxyl radicals play a significant role in the formation and progression of CVD as they can instigate lipid peroxidation, resulting in cellular damage and inflammatory responses. However, precisely detecting hydroxyl radicals in CVD lesions presents significant challenges due to their high reactivity and short lifespan. Herein, we present the development and application of a novel activatable optical probe, Cy-OH-LP, designed to detect hydroxyl radicals in lipid-rich environments specifically. Built on the Cy7 molecular skeleton, Cy-OH-LP exhibits near-infrared absorption and fluorescence characteristics, and its specific response to hydroxyl radicals enables a turn-on signal in both photoacoustic and fluorescence spectra. The probe demonstrated excellent selectivity and stability in various tests. Furthermore, Cy-OH-LP was successfully applied in an in vivo model to detect hydroxyl radicals in mouse models, providing a potential tool for diagnosing and monitoring AS. The biosafety of Cy-OH-LP was also verified, showing low cytotoxicity and no significant organ damage in mice. The findings suggest that Cy-OH-LP is a promising tool for the specific detection of hydroxyl radicals in lipid-rich environments, providing new possibilities for research and clinical applications in the field of oxidative stress-related diseases.

Lipoic acid-functionalized platycodin D nanocarrier improves mitochondrial dysfunction and reverses diabetes

The prevalence of metabolic syndrome, particularly type 2 diabetes mellitus (T2DM), is steadily increasing on a global scale. It is widely acknowledged that multi-organ insulin resistance serves as the central pathological mechanism underlying T2DM. Mitochondrial dysfunction is recognized as a significant contributor to insulin resistance, with a focus on maintaining homeostasis and addressing cellular functional impairments. In recent years, the emergence of natural compounds has shed light on the potential of platycodin D (PD) in the realm of diabetes management. However, optimizing its bioavailability and targeted delivery within the intricate gastrointestinal system remains a critical challenge. This study involved the development of PD nanocarriers (PD NPs) through an enzymatic reaction, followed by lipoic acid esterification onto PD NPs to create mitochondrial-functionalized nanocarriers (PA NPs). Cell experiments demonstrated that PA NPs effectively targeted mitochondria and mitigated cellular oxidative damage. In vitro simulations revealed that PA NPs successfully navigated the gastric environment and reached the intestinal tract for controlled release. Animal studies showcased that PA NPs improved islet morphology and function, and its mechanism may be achieved by regulating the GSK3-β/IRS1/AMPK signal pathway cascade. Furthermore, PA NPs modulated the gut microbiota derangement in STZ-induced diabetic mice, driving a healthier state, species evenness, and abundance.

Phospholipids, Sphingolipids, and Cholesterol-Derived Lipid Mediators and Their Role in Neurological Disorders.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol, and proteins. In response to cell stimulation or injury, the metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahexaenoic acid from the sn-2 position of the glycerol moiety by the action of phospholipases A2. Arachidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotrienes, and thromboxane are also involved in cell proliferation, differentiation, blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell protective effects. Sphingolipid-derived metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes, including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hydroxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

Cyclo(Pro-Tyr) elicits conserved cellular damage in fungi by targeting the [H+]ATPase Pma1 in plasma membrane domains

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes.

Dexmedetomidine alleviates CoCl2-induced hypoxic cellular damage in INS-1 cells by regulating autophagy.

Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic β-cell damage by regulating autophagy under hypoxia. INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine. Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1. Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.

A-170 Hypereosinophilic Syndrome and t(5;15): Case Report and Literature Review

Abstract Background Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent eosinophilia (absolute eosinophil count >1,500/mm3), classified into primary/clonal, reactive and idiopathic. After ruling out secondary causes of eosinophilia (parasitic infections, allergic conditions, vasculitis and collagenosis, drugs, eosinophilic lung disease, allergic gastroenteritis and metabolic conditions such as adrenal insufficiency), the main hypotheses become oncohematological diseases. Main entities to consider are myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, FDGFRB, FGFR1 or PCM1-JAK2 and chronic eosinophilic leukemia. Conventional and molecular cytogenetics are the basis for classification and diagnosis of various hematological malignancies. This report describes a rare case of HES with t(5;15) (q33;q22). Methods A 29-year-old male patient was admitted with leukocytosis with the following exams: hemoglobin 6.5g/dL, hematocrit 21.7%, platelets 71,000/mm3, leukocytes 56,190/mm3 (60% neutrophils with a left shift to pro-myelocyte; 6% monocytes and 24% eosinophils), DHL 277 U/L, B12 vitamin 932 pg/mL, folic acid 1.72ng/mL, ferritin 913ng/mL. Non-reactive results were detected for antinuclear antibody, rheumatoid Factor, HIV, hepatitis B and C, syphilis and chagas disease. Bone marrow was hypercellular for age with absolute granulocytic predominance (G:E ratio 64:1) and eosinophilia (38%) in all maturational stages without dysplasia. Bone marrow flow cytometry did not detect neither increases in blasts nor anomalous immunophenotype. Bone marrow biopsy demonstrated 99% cellularity with normal blasts. Cytogenetics with translocation between the long arms of chromosome 5 and 15 in 15 of 20 metaphases analyzed - 46,XY,t(5;15)(q33;q22). No other molecular tests were available for this patient. Results In the case described t(5;15)(q33;q22) was found, which may be related to the TP53BP1::PDGFRB gene rearrangement. This breakpoint generates a chimeric oncoprotein similar to other tyrosine kinase fusions responsive to Imatinib. 53BP1 is a cellular DNA damage response component that binds wild type (non-mutant) p53. Oncogenesis occurs since the coiled-coil domains of TP53BP1 can mediate the homodimerization of PDGFRB and the constitutive activation of its tyrosine kinase activity; on the other hand, the DNA damage response of TP53BP1 may be disrupted. Gene rearrangements involving PDGFRA and FDGFRB are associated with response to tyrosine kinase inhibitors. Elevated vitamin B12 is a common finding in myeloproliferations with eosinophilia due to the increased production of haptocorrins, which binds to vitamin B12 in serum and in other tissues. Conclusions To our knowledge, in the literature there is only one described case of Myeloproliferative Neoplasia with Eosinophilia related to t(5;15)(q33;q22).

Gold nanoclusters stabilized with dopa-containing ligands: Catalyst-indicator integrated probe for tumor cell screening

Elevated hydrogen peroxide (H2O2) levels not only inflict cellular damage but also serve as a harbinger for various diseases. Tumor cells, in particular, often exhibit an abundance of H2O2. Hence, the detection of this pivotal molecule assumes paramount importance in monitoring physiological states and expediting cancer diagnosis. To this end, we have ingeniously devised an enzyme-free and monomeric system for intracellular H2O2 detection. Our astute selection of dopa-containing peptidomimetics, replete with ortho-bisphenol and amino acid moieties, has engendered the synthesis of distinctive fluorescent gold nanoclusters (AuNCs). These nanoclusters not only function as a peroxidase-like catalyst, catalyzing the decomposition of H2O2 into hydroxyl radicals (·OH), but also serve as an indicator, with their fluorescence quenched in response to varying H2O2 concentrations. Experimental results evince that our GDpE-AuNCs exhibit remarkable sensitivity, boasting a detection limit of 0.49 μM and a linear range of 5–1000 μM. Moreover, the amalgamation of catalyst and indicator within a single structure, facilitating efficient cellular uptake, engenders intracellular H2O2 detection and discernment of tumor cells. This pioneering approach bequeaths a valuable assay probe for monitoring physiological states and ushering in early disease diagnosis.

Sustainable Fabrication of Luminescent Zinc Oxide Nanoparticles From Cucumis melo Fruit Peel Extract as Prospective Photocatalytic and Antigermicidal Agent.

The focus of current advances in nanotechnology has shifted significantly towards environmentally conscious methods that use harmless ingredients and moderated reaction circumstances to promote equitable development. Zinc oxide nanoparticles (NPs) currently grabbed attention of multiple medical fields owing to their unique ability to safeguard against cellular damage and alleviate serious human diseases via processes related to metabolism. This work focused on the generation of ZnO NPs using the peel of Cucumis melo fruit. The NPs were then analyzed and characterized using UV-Vis spectroscopy. The results indicated that at a wavelength of 352 nm, it was proven that the biosynthesis of ZnO NPs had occurred. The XRD pattern indicated the presence of dense crystal structures. The field emission scanning electron microscope (FE-SEM) picture confirmed the existence of polygonal-shaped ZnO NPs. The findings indicate that the produced ZnO NPs possess tough antibacterial properties against Gram-positive and Gram-negative microorganisms. When the ZnO NPs were exposed to direct sunshine for 80 min, they showed an 89% dye breakdown efficiency. This research specifically focused on the decomposition of reactivity dyes, with methylene blue dye being used as the target dye. The work demonstrates that the biosynthesis of ZnO NPs has a crucial and versatile role in the biological and environmental sectors.

Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection

BackgroundRespiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood. MethodsWe used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium. ResultsInfant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines. ConclusionsOur data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.

Human anti-apoptotic Bcl-2 and Bcl-xL proteins protect yeast cells from aging induced oxidative stress

Aging is a degenerative, biological, and time-dependent process that affects all organisms. Yeast aging is a physiological phenomenon characterized by the progressive transformation of yeast cells, resulting in modifications to their viability and vitality. Aging in yeast cells is comparable to that in higher organisms in some respects; however, due to their straightforward and well-characterized genetic makeup, these cells present unique advantages when it comes to researching the aging process. Here, we assessed the impact of human anti-apoptotic Bcl-2 and Bcl-xL proteins on aging using a yeast model. The findings clearly showed that these proteins exhibited remarkable anti-aging properties in yeast cells. Our data indicate that the presence of both proteins enhanced the reproductive survival of aging cells, likely by effecting the components functioning as both pro- and anti-oxidants, depending on the stage of yeast cell lifespan. Both proteins partially protected yeast cells from aging-related morphological deformations and cellular damage during the aging period. In particular, Bcl-xL expressing yeast cells reached the maximum activity levels for almost all of the major antioxidant enzymes and the total antioxidant status on the 8th day of lifespan and could provide effective protection at the latest stage of the investigated aging period. The chemometric data analysis of IR spectra confirmed the findings of the morphological and biochemical analyses. In this regard, specifically, understanding the mechanism of action on the cellular redox state of Bcl-xL in yeast may facilitate comprehension of its indirect antioxidant function in higher eukaryotes.

A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy: Reassessment of spinal cord pathology.

Spinal muscular atrophy (SMA) is a life-limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success. As opportunities to study treatment-naïve tissue decrease, we have characterised spinal cord pathology in severe infantile SMA using gold-standard techniques, providing a baseline to measure treatment success and therapeutic limitations. Detailed histological analysis, stereology and transmission electron microscopy were applied to post-mortem spinal cord from severe infantile SMA patients to estimate neuron number at the end of life; characterise the morphology of ventral horn, lateral horn and Clarke's column neuron populations; assess cross-sectional spinal cord area; and observe myelinated white matter tracts in the clinically relevant thoracic spinal cord. Ventral horn neuron loss was substantial in all patients, even the youngest cases. The remaining ventral horn neurons were small with abnormal, occasionally chromatolytic morphology, indicating cellular damage. In addition to ventral horn pathology, Clarke's column sensory-associated neurons displayed morphological features of cellular injury, in contrast to the preserved sympathetic lateral horn neurons. Cellular changes were associated with aberrant development of grey and white matter structures that affected the overall dimensions of the spinal cord. We provide robust quantification of the neuronal deficit found at the end of life in SMA spinal cord. We question long-accepted dogmas of SMA pathogenesis and shed new light on SMA neuropathology out with the ventral horn, which must be considered in future therapeutic design.

Purification of mulberry anthocyanins by macroporous resin and its protective effect against H2O2-induced oxidative stress in vascular endothelial cells

Vascular endothelial cells (VECs), which are cells located in the inner layer of the vessel wall, maintain the homeostasis of the microenvironment; however, a large accumulation of reactive oxygen species can cause cellular damage. In this study, mulberry anthocyanins were enriched and purified by macroporous resin; the protective effect of mulberry anthocyanins against H2O2-induced injury to VECs was investigated. The results showed AB-8 macroporous resin was suitable for the purification of mulberry anthocyanins, the purity was as high as 82.37% ± 1.79%. Mulberry anthocyanins were effective in restoring H2O2-induced reduction in vascular cell viability, and showcased protective effects against apoptosis. Meanwhile, mulberry anthocyanins increased SOD activity, while it decreased the level of MDA and Xanthine oxidase-1 (XO-1), thus further enhancing the antioxidant defense of VECs. This shows that mulberry anthocyanins can be used as antioxidants and play a positive role in the prevention of cardiovascular diseases, and have certain development value.

Performance Study and Application of Antioxidant Peptides CHCIWM and CHCPWM

AbstractWhen the level of reactive oxygen species (ROS) increases abnormally in the body, it damages tissue cells and is closely related to the occurrence of various chronic diseases. Antioxidant peptides (APs) are a class of active short peptides with antioxidant capacity, which have great research value. In this paper, two APs were designed and synthesized based on the structural features of APs: CHIWM (AP1) and CHCPWM (AP2). The reactive sites and activities of APs were analyzed using the quantum chemical density functional theory (DFT) method. The reactive sites are all located in the indolyl heterocycle of tryptophan residues, among which AP1 has a smaller energy gap and single point energy. Multiple free radical scavenging assays showed that AP1 and AP2 had stronger antioxidant activity than the positive control, glutathione (GSH). For scavenging DPPH free radicals, the IC50s values were 0.613 mg/mL and 0.606 mg/mL, respectively. In cellular assays, both AP1 and AP2 were able to scavenge ROS in the cells and attenuate cellular damage. In conclusion, AP1 and AP2 designed in this paper have good antioxidant activity and have the potential to be applied in the treatment of chronic diseases caused by cellular oxidative damage.

Effects of α-olefin sulfonate (AOS) on Tubifex tubifex: toxicodynamic-toxicokinetic inferences from the general unified threshold (GUTS) model, biomarker responses and molecular docking predictions.

We investigated the potential ecological risks and harm to aquatic organisms posed by anionic surfactants such as α-olefin sulfonate (AOS), which are commonly found in industrial and consumer products, including detergents. This study assessed acute (96-h) and subchronic (14-day) responses using antioxidant activity, protein levels, and histopathological changes in Tubifex tubifex exposed to different AOS concentrations (10% of the LC50, 20% of the LC50, and a control). Molecular docking was used to investigate the potential interactions between the key stress biomarker enzymes (superoxide dismutase, catalase, and cytochrome c oxidase) of Tubifex tubifex. Acute AOS exposure showed a concentration-dependent decrease in survival, and the general unified threshold (GUTS) model revealed that survivorship is linked to individual response patterns rather than random (stochastic) fluctuations. The GUTS model also revealed dose-dependent toxicity patterns in Tubifex tubifex exposed to α-olefin sulfonate (AOS), with adaptive mechanisms at lower concentrations but significant increases in mortality beyond a certain threshold, emphasizing the role of the AOS concentration in shaping its toxicological impact. Exposure to AOS disrupted antioxidant activity, inducing oxidative stress, with GST and GPx showing positive associations with surfactant concentration and increased lipid peroxidation (elevated MDA levels); moreover, AOS exposure decreased protein concentration, signifying disturbances in vital cellular processes. Histopathological examinations revealed various tissue-level alterations, including cellular vacuolation, cytoplasmic swelling, inflammation, necrosis, and apoptosis. Molecular docking analysis demonstrated interactions between AOS and enzymes (-catalase, superoxide dismutase, and cytochrome c oxidase) in Tubifex tubifex, including hydrophobic and hydrogen bond interactions, with the potential to disrupt enzyme structures and activities, leading to cellular process disruptions, oxidative stress, and tissue damage. According to the species sensitivity distribution (SSD), the difference in toxicity between Tilapia melanopleura (higher sensitivity) and Daphnia magna (low sensitivity) to AOS suggests distinct toxicokinetic and toxicodynamic mechanisms attributable to more complex physiology in Tilapia and efficient detoxification in Daphnia due to its smaller size.

Effect of Cd2+ and Cu2+ on Desulfovibrio vulgaris strain ATCC 7757: Insights from sulfur isotope fractionation

Microbial sulfate reduction (MSR) is the predominant microbial metabolic process involved in sulfur cycling in metal-sulfide mining areas. In this study, we investigated the effect of Cd2+ and Cu2+ on MSR driven by Desulfovibrio vulgaris strain ATCC 7757, determined the corresponding sulfur isotope compositions to establish a fundamental relationship between toxicity and isotope fractionation. Cd2+ did not cause significant cellular irrecoverable damage until concentrations exceeded 3.5 ppm, and the bacteria would enhance the transfer of SO42- to APS to ensure the bacterial growth. The repair of DNA damage caused by Cd2+ was a gradually stimulated process, which resulted in a tolerance period. Cu2+ inhibited MSR in a dose-dependent manner at concentrations below 1 ppm, and the bacterial growth significantly inhibited. When exposed to 1 ppm Cu2+ for 48h, ATCC 7757 might enhance the substrates transport to maintain its culturability through up-regulating genes encoding H+-transporting ATPase, ABC transporters and Protein export. Cd2+ had minimal impact on δ34Ssulfate, with an enrichment factor (34ε) ranging from -11.7‰ to -12.3‰. Conversely, Cu2+ significantly affected the δ34Ssulfate (34ε = -11.1‰ to -15.4‰), resulting in a substantial decrease in δ34Ssulfide, with the lowest value of δ34Ssulfide recorded as -18.8‰ (-11.5‰ for control group). The study demonstrated that sulfur isotope fractionation could indicate different toxicity mechanisms of heavy metal on ATCC 7757, aiding in the identification of environmental contamination caused by heavy metals.