Oxidative Stress Response Research Articles

Role of Flavonoids in Modulation of Mitochondria Dynamics during Oxidative Stress.

Flavonoids are a widespread category of naturally occurring polyphenols distinguished by the flavan nucleus in plant-based foods and beverages, known for their various health benefits. Studies have suggested that consuming 150-500 mg of flavonoids daily is beneficial for health. Recent studies suggest that flavonoids are involved in maintaining mitochondrial activity and preventing impairment of mitochondrial dynamics by oxidative stress. This review emphasized the significance of studying the impact of flavonoids on mitochondrial dynamics, oxidative stress, and inflammatory response. This review analysed and summarised the findings related to the impact of flavonoids on mitochondria from publicly available search engines namely Pubmed, Scopus, and Web of Science. Any disruption in mitochondrial dynamics can contribute to cellular dysfunction and diseases, including cancer, cardiac conditions, and neurodegeneration. Flavonoids have been shown to modulate mitochondrial dynamics by regulating protein expression involved in fission and fusion events. Furthermore, flavonoids exhibit potent antioxidant properties by lowering the production of ROS and boosting the performance of antioxidant enzymes. Persistent inflammation is a characteristic of many different disorders. This is because flavonoids also alter the inflammatory response by controlling the expression of numerous cytokines and chemokines involved in the inflammatory process. Flavonoids exhibit an impressive array of significant health effects, making them an effective therapeutic agent for managing various disorders. Further this review summarised available mechanisms underlying flavonoids' actions on mitochondrial dynamics and oxidative stress to recognize the optimal dose and duration of flavonoid intake for therapeutic purposes. This review may provide a solid foundation for developing targeted therapeutic interventions utilizing flavonoids, ultimately benefiting individuals afflicted with various disorders.

Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans

Gelsemium elegans Benth. (G. elegans) is a traditional medicinal herb that has anti-inflammatory, analgesic, sedative, and detumescence effects. However, it can also cause intestinal side effects such as abdominal pain and diarrhea. The toxicological mechanisms of gelsenicine are still unclear. The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans (C. elegans). The nematodes were treated with gelsenicine, and subsequently their growth, development, and locomotion behavior were evaluated. The targets of gelsenicine were predicted using PharmMapper. mRNA-seq was performed to verify the predicted targets. Intestinal permeability, ROS generation, and lipofuscin accumulation were measured. Additionally, the fluorescence intensities of GFP-labeled proteins involved in oxidative stress and unfolded protein response in endoplasmic reticulum (UPRER) were quantified. As a result, the treatment of gelsenicine resulted in the inhibition of nematode lifespan, as well as reductions in body length, width, and locomotion behavior. A total of 221 targets were predicted by PharmMapper, and 731 differentially expressed genes were screened out by mRNA-seq. GO and KEGG enrichment analysis revealed involvement in redox process and transmembrane transport. The permeability assay showed leakage of blue dye from the intestinal lumen into the body cavity. Abnormal mRNAs expression of gem-4, hmp-1, fil-2, and pho-1, which regulated intestinal development, absorption and catabolism, transmembrane transport, and apical junctions, was observed. Intestinal lipofuscin and ROS were increased, while sod-2 and isp-1 expressions were decreased. Multiple proteins in SKN-1/DAF-16 pathway were found to bind stably with gelsenicine in a predictive model. There was an up-regulation in the expression of SKN-1:GFP, while the nuclear translocation of DAF-16:GFP exhibited abnormality. The UPRER biomarker HSP-4:GFP was down-regulated. In conclusion, the treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

Diesel exhaust particulate matter induces GC-1 spg cells oxidative stress by KEAP1-NRF2 pathway and inhibition of ATP5α1 S-sulfhydration

Diesel exhaust particle (DEP) exposure induces a variety of toxicological effects through oxidative stress and inflammation responses. This research investigated the mechanisms underlying DEP-induced GC-1spg cells oxidative stress by examining ROS accumulation, antioxidant defense systems activation, mitochondrial dysfunction, and the Nrf2/Keap1/HO-1 pathway response. Subsequently, we further evaluated the ATP levels, ATP5α synthase activity and ATP5α synthase S-sulfhydrated modification in DEP-exposed GC-1 spg cells. The results showed that DEP exposure significantly inhibited cell proliferation and viability, increased intracellular ROS production, decreased MMP, down-regulated antioxidant capacity, activated the Nrf2/Keap1/HO-1 pathway. However, DEP-induced oxidative stress was partially alleviated by GSH and exogenous H2S. In addition, DEP exposure induced ATP depletion and ATP5α synthase inactivity in GC-1 spg cells, accompanied by ATP5α synthase S-sulfhydrated modification. In conclusion, our research showed that DEP may incapacitate mitochondria through oxidative stress injury, leading to GC-1 spg cells oxidative stress. This process may be associated with the reduction of ATP5α1 S-sulfhydrated modification. It provides a new perspective for the research of the mechanism related to male reproductive toxicity due to air pollution.

β-Caryophyllene promotes the survival of random skin flaps by upregulating the PI3K/AKT signaling pathway

BackgroundFlap transplantation is a widely used plastic repair technique in surgical procedures, aimed at addressing skin defects resulting from diverse wounds and diseases. However, due to the insufficient blood supply after flap surgery, the occurrence of ischemia-reperfusion injury, and an excessive sterile inflammatory response, flaps frequently develop complications (e.g., partial or complete ischemic necrosis). These complications have adverse effects on wound healing and repair. β-Caryophyllene (BCP) is a bicyclic sesquiterpene that is widely present in plants. It mitigates oxidative stress and inflammatory responses, demonstrates neuroprotective and analgesic properties, and serves a protective function in organs or tissues subjected to ischemia-reperfusion injury. However, no study has confirmed whether BCP can be used in the field of flap transplantation to improve the flap survival rate. MethodsTo assess the impact of BCP on random flap survival, we constructed a modified McFarlane random flap model on the rat. After 7 consecutive days of gavage with different doses of BCP, we measured the survival area ratio, angiogenesis, blood perfusion, tissue inflammation level, apoptosis-related protein levels, and the PI3K/AKT signaling pathway expression of the random flap. ResultsBCP treatment increased the survival area of the flap in a dose-dependent manner after random flap transplantation in rats. BCP mainly promoted the formation of tissue blood vessels, improved flap blood perfusion, limited the local inflammatory response, and reduced apoptosis. In addition, we demonstrated that BCP works primarily by promoting the PI3K/AKT signaling expression while enhancing the phosphorylation of AKT. Administration of wortmannin, a selective inhibitor of PI3K, eliminated the effects of BCP. ConclusionBCP can promote the survival of random flaps by upregulating the PI3K/AKT signaling pathway, increasing tissue blood perfusion, and limiting the inflammatory response and apoptosis.

Supercritical carbon dioxide and ethanol-assisted extraction of bioactive compounds from Bourbon, Catimor, and Caturra coffee pulp for maximized antioxidant and therapeutic properties

Coffee pulp waste contains valuable bioactive components that are often discarded, leading to environmental impact. The optimum level of supercritical (50% CO2: ethanol) extraction (SFE) condition revealed the highest yield% and antioxidant activity assayed by 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) in coffee peel compared to hot water (85°C), and 80% ethanol. Additionally, the optimized SFE condition at 60°C, 300 Bar, and 60 min showed the highest yield (p>0.05), and antioxidant activity of Bourbon, Caturra and Catimor coffee pulp extracts (CPE). Cell-based experiments unveiled the fascinating biological effects of the CPE. Cytotoxicity in both RAW 264.7 and HepG-2 cells, indicating their potential to trigger apoptosis, all the while demonstrating anti-inflammatory properties. Among the different coffee varieties, Caturra consistently exhibited the highest level of biological activity. The Western blot analysis further elucidated the extracts' capacity to influence critical cellular markers linked to oxidative stress, inflammation, and antioxidant responses, with the unaltered NF-kB expression implying a targeted impact on specific cellular pathways. Therefore, SFE using 50% CO2: ethanol ratios could extract the maximum phytochemicals and impart excellent functional properties as a functional ingredient for food fortification.

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cows' energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, d 7, d 14, and d 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to LC-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between 2 groups. Serum BHBA, glucose, leptin, aspartate aminotransferase, IL-6, and TNF-α were greater in cows with HFM than in LFM. Serum adiponectin, revised quantitative insulin sensitivity check index and albumin were lower in cows with HFM than LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrices (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.

Bacillus cereus CwpFM induces colonic tissue damage and inflammatory responses through oxidative stress and the NLRP3/NF-κB pathway

Bacillus cereus (B. cereus) from cow milk poses a threat to public health, causing food poisoning and gastrointestinal disorders in humans. We identified CwpFM, an enterotoxin from B. cereus, caused oxidative stress and inflammatory responses in mouse colon and colonic epithelial cells. Colon proteomics revealed that CwpFM elevated proteins associated with inflammation and oxidative stress. Notably, CwpFM induced activation of the NLRP3/NF-κB signaling, but suppressed antioxidant NFE2L2/HO-1 expression in the intestine and epithelial cells. Consistently, CwpFM exposure led to cytotoxicity and ROS accumulation in Caco-2 cells in a dose-dependent manner. Further, NAC (ROS inhibitor) treatment abolished NLRP3/NF-κB activation due to CwpFM. Moreover, overexpression of Nfe2l2 or activation of NFE2L2 by NK-252 reduced ROS production and inhibited activation of the NLRP3/NF-κB pathway. Inhibition of NF-κB by ADPC and/or suppression of NLRP3 by MCC950 attenuated CwpFM-induced inflammatory responses in Caco-2 cells. Collectively, CwpFM induced oxidative stress and NLRP3/NF-κB activation by inhibiting the NFE2L2/HO-1 signaling and ROS accumulation, leading to the development of intestinal inflammation. Our data elucidate the role of oxidative stress and innate immunity in CwpFM enterotoxicity and contribute to developing diagnostic and therapeutic products for B. cereus-related food safety issues.

Combined contamination of microplastic and antibiotic alters the composition of microbial community and metabolism in wheat and maize rhizosphere soil

The widespread application of antibiotics and plastic films in agriculture has led to new characteristics of soil pollution. The impacts of combined contamination of microplastics and antibiotics on plant growth and rhizosphere soil bacterial community and metabolisms are still unclear. We conducted a pot experiment to investigate the effects of polyethylene (0.2%) and norfloxacin/doxycycline (5mgkg–1), as well as the combination of polyethylene and antibiotics, on the growth, rhizosphere soil bacterial community and metabolisms of wheat and maize seedlings. The results showed that combined contamination caused more serious damage to plant growth than individual contamination, and aggravated root oxidative stress responses. The diversity and structure of soil bacterial community were not markedly altered, but the composition of the bacterial community, soil metabolisms and metabolic pathways were altered. The co-occurrence network analysis indicated that combined contamination may inhibit the growth of wheat and maize seedings by simplifying the interrelationships between soil bacteria and metabolites, and altering the relative abundance of specific bacteria genera (e.g. Kosakonia and Sphingomonas) and soil metabolites (including sugars, organic acids and amino acids). The results help to elucidate the potential mechanisms of phytotoxicity of the combination of microplastic and antibiotics.

Dissolved oxygen facilitates efficiency of chlorine disinfection for antibiotic resistance

Controlling the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) is a global concern. While commonly used chlorine disinfectants can damage or even kill ARB, dissolved oxygen (DO) may affect the formation of reactive chlorine species. This leads to the hypothesis that DO may play roles in mediating the effectiveness of chlorine disinfection for antibiotic resistance. To this end, this study investigated the impacts of DO on the efficiency of chlorine disinfection for antibiotic resistance. The results revealed that DO could increase the inactivation efficiency of ARB under chloramine and free chlorine exposure at practically relevant concentrations. Reactive species induced by DO, including H2O2, O2−, and OH, inactivated ARB strains by triggering oxidative stress response and cell membrane damage. In addition, the removal efficiency of extracellular ARGs (i.e. tetA and blaTEM) was enhanced with increasing dosage of free chlorine or chloramine under aerobic conditions. DO facilitated the fragmentation of plasmids, contributing to the degradation of extracellular ARGs under exposure to chlorine disinfectants. The findings suggested that DO facilitates disinfection efficiency for antibiotic resistance in water treatment systems.

Multi-mechanism antitumor/antibacterial effects of Cu-EGCG self-assembling nanocomposite in tumor nanotherapy and drug-resistant bacterial wound infections

Chemotherapy and surgery stand as primary cancer treatments, yet the unique traits of the tumor microenvironment hinder their effectiveness. The natural compound epigallocatechin gallate (EGCG) possesses potent anti-tumor and antibacterial traits. However, the tumor’s adaptability to chemotherapy due to its acidic pH and elevated glutathione (GSH) levels, coupled with the challenges posed by drug-resistant bacterial infections post-surgery, impede treatment outcomes. To address these challenges, researchers strive to explore innovative treatment strategies, such as multimodal combination therapy. This study successfully synthesized Cu-EGCG, a metal-polyphenol network, and detailly characterized it by using synchrotron radiation and high-resolution mass spectrometry (HRMS). Through chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT), Cu-EGCG showed robust antitumor and antibacterial effects. Cu+ in Cu-EGCG actively participates in a Fenton-like reaction, generating hydroxyl radicals (·OH) upon exposure to hydrogen peroxide (H2O2) and converting to Cu2+. This Cu2+ interacts with GSH, weakening the oxidative stress response of bacteria and tumor cells. Density functional theory (DFT) calculations verified Cu-EGCG’s efficient GSH consumption during its reaction with GSH. Additionally, Cu-EGCG exhibited outstanding photothermal conversion when exposed to 808 nm near-infrared (NIR) radiation and produced singlet oxygen (1O2) upon laser irradiation. In both mouse tumor and wound models, Cu-EGCG showcased remarkable antitumor and antibacterial properties.

Coronary Vascular Rarefaction in Heart Failure

Coronary vasculature rarefaction has been thought to play a role in the development of heart failure (HF), causing reduced myocardial perfusion; understanding the role that coronary rarefaction plays within HF presents an avenue for therapeutic strategies. We assessed the coronary microvascular and small vessel networks in left atrial appendage (LAA) samples to determine differences based on HF status. LAA samples were obtained from 15 consecutive patients during cardiac surgery (BMI: 22.8-37.9, age: 51-82, M:F: 9:6, NonHF:HF: 11:4). LAA samples were paraffn-embedded or flash frozen whereby 40 μm thick sections were then immunolabelled using DyLight 594 fluorescent tomato-lectin dye and z-stack images were rendered using microscopy. Z-stack images were input into Vesselucida360 and the vessel networks were three-dimensionally reconstructed via unbiased automatic tracing with multiple quantitative endpoints calculated. LAA samples were also used for proteomic analysis via LC-MS followed by statistical and pathway analyses to determine differences in protein expression and pertinent pathways as well as in a wide-scale gene expression array (NanoString) to further study underlying molecular targets. We found that the number of branching nodes and total vessel length in the coronary vascular network was decreased in HF compared to NonHF patients. Whereas the total volume and surface area were similar between HF and NonHF patients. Proteomic analysis and principal component analysis identified differences in protein profiles in the two groups, with pathway analysis identifying cardiac contraction and metabolism, along with hydrogen peroxide catabolic pathways downregulated in HF. Gene expression profiling identified numerous hypoxia response and oxidative stress response markers as downregulated in HF LAA samples. The data obtained show coronary vascular rarefaction occurring in HF patients, implying potential implications in the progression of HF. Additionally, proteomic data point to the downregulation of hydrogen peroxide response pathways as a potential mechanism for coronary microvascular rarefaction that we want to elucidate in future studies. T32 HL155011 (KAF) F31 NS132564 (KAF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

IRE1α regulates ROS and immune responses after UVB irradiation

UV irradiation of the skin induces photo damage and generates cytotoxic intracellular reactive oxygen species (ROS), activating the unfolded protein response (UPR) to adapt or reduce these UVB-mediated damages. We previously identified a role for the key UPR mediator inositol requiring enzyme 1 (IRE1α) in the UV-DNA damage response. Here, we show that in the absence of IRE1α, PERK activity and protein levels are significantly compromised following UVB irradiation. Additionally, the loss of IRE1α suppressed phosphorylation of the PERK target, nuclear factor erythroid-2-related factor 2 (NRF2), and NRF2-dependent antioxidant gene expression after UVB irradiation. Interestingly, IRE1α-deficient keratinocytes exhibit elevated basal ROS levels, while a robust ROS induction upon UVB exposure is abolished. Because UVB-induced ROS plays an essential role in regulating skin inflammation, we analyzed recruited immune cell populations and the expression of pro-inflammatory cytokines, Il-6 and Tnfα in mice with epidermally-targeted deletion of Ire1α. Following UVB irradiation, there was significantly less recruitment of neutrophils and leukocytes and reduced expression of pro-inflammatory cytokine genes in the skin of mice lacking IRE1α. Furthermore, keratinocyte proliferation was also significantly reduced after chronic UVB exposure in the skin of these mice. Collectively, our findings indicate that IRE1α is essential for basal and UVB-induced oxidative stress response, UV-induced skin immune responses, and keratinocyte proliferation. These findings shed new light on the protective function of IRE1α in the response to UV.

Captopril's influence on Danio rerio embryonic development: Unveiling significant toxic outcomes at environmentally relevant concentrations

Anticipating a global increase in cardiovascular diseases, there is an expected surge in the use of angiotensin-converting enzyme inhibitors, notably captopril (CAP). This heightened usage raises significant environmental apprehensions, mainly due to limited knowledge regarding CAP's toxic effects on aquatic species. In response to these concerns, the current study aimed to tackle this knowledge gap by evaluating the potential influence of nominal concentrations of CAP (0.2–2000 μg/L) on the embryonic development of Danio rerio. The findings revealed that CAP at all concentrations, even at concentrations considered environmentally significant (0.2 and 2 μg/L), induced various malformations in the embryos, ultimately leading to their mortality. Main malformations included pericardial edema, craniofacial malformation, scoliosis, tail deformation, and yolk sac deformation. In addition, CAP significantly altered the antioxidant activity of superoxide dismutase and catalase across all concentrations. Simultaneously, it elevated lipid peroxidation levels, hydroperoxides, and carbonylic proteins in the embryos, eliciting a substantial oxidative stress response. Likewise, CAP, at all concentrations, exerted significant modulatory effects on the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3), organogenesis (tbx2a, tbx2b, and irx3b), and ion exchange (slc12a1 and kcnj1) in Danio rerio embryos. Both augmentation and reduction in the expression levels of these genes characterized this modulation. The Pearson correlation analysis indicated a close association between oxidative damage biomarkers and the expression patterns of all examined genes with the elevated incidence of malformations and mortality in the embryos. In summary, it can be deduced that CAP poses a threat to aquatic species. Nevertheless, further research is imperative to enhance our understanding of the environmental implications of this pharmaceutical compound.

Cardiomyocyte Derived Extracellular Mitochondria in Inflammatory Response During Oxidative Stress

Increased production of reactive oxygen species (ROS) occurs in a variety of disease states. Elevated oxidative stress often co-exists with inflammatory response. A burst of ROS production due to myocardial ischemia or infarction causes damage to the mitochondria, tissue injury and inflammation. The mitochondria have evolved with quality control mechanisms to maintain the homeostasis for energy metabolism, and to control cell death. We have found secretion of mitochondria as a novel mechanism of mitochondrial quality control and for cell-cell communication. Sublethal doses of H2O2 cause an increased release of mitochondria from cardiomyocytes to the extracellular space. Extracellular mitochondria (EM) appear to be smaller with an average diameter of 524.67±54.69nm (control) and 563.27±41.82nm (H2O2 treated cells), compared to the corresponding intracellular mitochondria (IM) having an average diameter of 1192±256.50nm and 818.37±62.74 nm. LC-MS/MS based proteomics showed an increased levels of peroxiredoxins and several respiratory chain proteins in the EM from stressed cells. However, metabolomics did not reveal significant changes in the EM metabolites collected from control or stressed cells. Both have reduced NAD, ATP, ADP, or AMP but increased nicotinamide, lactate, and a number of amino acids compared to the IM. Inhibiting ceramide synthesis, a sphingolipid derivative, reduced the number of EM released from oxidatively stressed cardiomyocytes, indicating a role of lipids in regulating mitochondrial release. Functionally, EM from oxidatively stressed cardiomyocytes caused activation of M1 and M2 macrophages, as measured by cytokine markers TNFα and CD163. Our data have unveiled a novel mechanism of oxidative stress response and secretion of the extracellular mitochondria as a vehicle for initiation of inflammatory response. NIH R01 GM125212, R01 GM126165, Holsclaw Endowment and the University of Arizona College of Pharmacy start-up fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Co-exposure of decabromodiphenyl ethane and cadmium increases toxicity to earthworms: Enrichment, oxidative stress, damage and molecular binding mechanisms

The increase of electronic waste worldwide has resulted in the exacerbation of combined decabromodiphenyl ethane (DBDPE) and cadmium (Cd) pollution in soil, posing a serious threat to the safety of soil organisms. However, whether combined exposure increases toxicity remains unclear. Therefore, this study primarily investigated the toxic effects of DBDPE and Cd on earthworms at the individual, tissue, and cellular levels under single and combined exposure. The results showed that the combined exposure significantly increased the enrichment of Cd in earthworms by 50.32-90.42%. The toxicity to earthworms increased with co-exposure, primarily resulting in enhanced oxidative stress, inhibition of growth and reproduction, intensified intestinal and epidermal damage, and amplified coelomocyte apoptosis. PLS-PM analysis revealed a significant and direct relationship between the accumulation of target pollutants in earthworms and oxidative stress, damage, as well as growth and reproduction of earthworms. Furthermore, IBR analysis indicated that SOD and POD were sensitive biomarkers in earthworms. Molecular docking elucidated that DBDPE and Cd induced oxidative stress responses in earthworms through the alteration of the conformation of the two enzymes. This study enhances understanding of the mechanisms behind the toxicity of combined pollution and provides important insights for assessing e-waste contaminated soils. Environmental ImplicationDBDPE and Cd are commonly used in electronic products. In recent years, the amount of these substances generated by electronic wastes has been increasing annually. However, their toxicity to soil organisms (such as earthworms) under combined exposure is unclear. The toxic effects of the two pollutants on the physiological, biochemical and molecular levels of earthworms were studied at individual, tissue and cell levels. The results showed that combined exposure increased the toxicity to earthworms and aggravated the tissue and cell damage. This study provides reference for assessing the risk of soil environment under the combined pollution of e-waste disposal areas.

Impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response post weaning time

Milk is a whitish liquid that is secreted from mammary glands; and considered as the primary source of nutrition for newborns since they are not able to digest solid food. However, it contains primary nutrients, as well as growth and immune factors. Early weaning is a critical issue that face women and their babies in developing countries. To avoid infant malnutrition, they tend to use other milk types instead of baby formula. Therefore, the present study aimed to evaluate the impact of cow, buffalo, goat or camel milk consumption on oxidative stress, inflammation and immune response in male and female Sprague Dawley rats post weaning time. The amino acids, fatty acids, minerals and vitamins in the tested milk types were evaluated. Animals were divided into 5 groups (control, cow, buffalo, goat and camel milk administrated groups) (10 rats/group); each animal was administrated by 3.4 ml/day. Rats were administered with milk for 6 weeks; at the end of the 5th week, five animals of each group were isolated and the remaining five animals were immunized with sheep red blood cells (SRBCs) and kept for another week to mount immune response. The effect of different milk types on rats’ immune response towards SRBCs was evaluated through pro-inflammatory cytokines, antioxidants, ESR and CRP measurement; together, with the histopathological examination of spleen samples and hemagglutination assay. Camel milk consumption reduced oxidative stress and inflammation in spleen that resulted from SRBCs immunization; in addition to, B cell stimulation that was apparent from the high level of anti-SRBCs antibodies. Camel milk is recommended for newborn consumption, due to its high-water content, unsaturated fatty acids, and vitamin C, as well as low lactose and fat content.

Network pharmacology and in vivo experiment-based strategy for investigating the mechanism of chronic prostatitis/chronic pelvic pain syndrome in QianLieJinDan tablets

BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. ObjectiveTo reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. MethodsThe concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. ResultsIn this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. ConclusionThe potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

Common snook (Centropomus undecimalis) juveniles maintained at high temperature and brackish water improve growth, osmoregulation, and antioxidant responses

The study evaluated the interactions between temperature (25 and 28 °C) and salinity (0, 15, and 32 ppt) on the growth performance, plasmatic ions, ATPases activities, and oxidative and antioxidant parameters in different tissues of common snook (Centropomus undecimalis) reared for 90 days by a 2 × 3 factorial design. The growth performance and feed conversion ratio were influenced by temperature and interaction between factors, with the best results observed in the combination between 28 °C and 15 ppt. There were effects of temperature and salinity (isolated or in interaction) for plasmatic ions, v-type H+-ATPase (VHA) and Na+/K+-ATPase (NKA) activities, and oxidative stress responses. Gill VHA (at 32 ppt) and NKA (at 0 and 15 ppt) activities were higher at 25 than at 28 °C. In the kidney, at 28 °C, the VHA (at 15 ppt) and NKA (at 32 ppt) activities were higher than at 25 °C. The VHA and NKA activities in the stomach at 28 °C and 32 ppt were higher than at the other treatments. In the intestine, the lowest activity of VHA at 25 and 28 °C occurred at 0 and 32 ppt, respectively, and the activity of NKA was highest in the interaction of 0 ppt and 25 °C. At 0 ppt, the plasmatic Na+ and Cl− values at both temperatures were decreased, and the plasmatic K+ values at 25 °C were increased. Liver thiobarbituric acid reactive substances and protein carbonyl content values were higher at the combinations of 15 ppt and 25 °C and 32 ppt and 28 °C than at the other interactions. Liver antioxidant responses (glutathione-S-transferase, glutathione peroxidase, non-protein thiols, and superoxide dismutase) were higher at 15 ppt than other salinities at both temperatures. In conclusion, the improved growth, osmoregulation, and antioxidant responses were found to be higher at 28 °C and 15 ppt.

Interfacial effects of perfluorooctanoic acid and its alternative hexafluoropropylene oxide dimer acid with polystyrene nanoplastics on oxidative stress, histopathology and gut microbiota in Crassostrea hongkongensis oysters

The increasing interfacial impacts of polystyrene nanoplastics (PS) and per- and polyfluoroalkyl substances (PFAS) complex aquatic environments are becoming more evident, drawing attention to the potential risks to aquatic animal health and human seafood safety. This study aims to investigate the relative impacts following exposure (7 days) of Crassostrea hongkongensis oysters to the traditional PFAS congener, perfluorooctanoic acid (PFOA) at 50 μg/L, and its novel alternative, hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX at 50 μg/L, in conjunction with fluorescent polystyrene nanoplastics (PS, 80 nm) at 1 mg/L. The research focuses on assessing the effects of combined exposure on oxidative stress responses and gut microbiota in the C. hongkongensis. Comparing the final results of PS + GenX (PG) and PS + PFOA (PF) groups, we observed bioaccumulation of PS in both groups, with the former causing more pronounced histopathological damage to the gills and intestines. Furthermore, the content of antioxidant enzymes induced by PG was higher than that of PF, including Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR) and Glutathione Peroxidase (GSH). Additionally, in both PG and PF groups, the expression levels of several immune-related genes were significantly upregulated, including tnfα, cat, stat, tlr-4, sod, and β-gbp, with no significant difference between these two groups (p > 0.05). Combined exposure induced significant changes in the gut microbiota of C. hongkongensis at its genus level, with a significant increase in Legionella and a notable decrease in Endozoicomonas and Lactococcus caused by PG. These shifts led to beneficial bacteria declining and pathogenic microbes increasing. Consequently, the microbial community structure might be disrupted. In summary, our findings contribute to a deeper understanding of the comparative toxicities of marine bivalves under combined exposure of traditional and alternative PFAS.

Polysaccharide from Hericium erinaceus improved laying performance of aged hens by promoting yolk precursor synthesis and follicle development via liver-blood-ovary axis

Little information is available on the effect of Hericium erinaceus polysaccharides (HEP) on laying hens, especially on improving liver and ovarian health and function. Therefore, this study was conducted to investigate the impacts of HEP on liver and ovarian function to delay the decline in the laying performance of aged hens. A total of 360 fifty-eight-wk-old laying hens were randomly allocated to 4 treatments, with 6 replicates of 15 birds each. After 2 wk of adaptation, the birds were fed basal diet (CON) or basal diets supplemented with 250, 500, and 750 mg/kg of HEP (HEP250, HEP500, and HEP 750, respectively) for 12 wk. The results showed that, compared with CON, hens fed HEP had significantly increased laying performance (P < 0.05) and promoted follicle development, as evidenced by the increased numbers of hierarchical follicles, small follicles, and total follicles (P < 0.05). Birds fed 500 mg/kg of HEP improved the liver function by increasing T-AOC activity (P < 0.05) and decreasing hepatic oxidative stress and inflammatory responses (inflammatory cell infiltration) caused by aging. The lipid metabolism was improved, and yolk precursor synthesis was promoted in the liver of HEP-treated laying hens by upregulating the mRNA expression of FAS, MTTP, PPAR-α, APOVLDL-Ⅱ, and VTG-Ⅱ (P < 0.05). In addition, HEP significantly decreased ovarian inflammation by regulating the mRNA levels of NF-κB, IL-1β, IL-6, and TNF-α (P < 0.05). As a result, the contents of E2, LH, and FSH in serum and the gene expression of ERα of the liver and FSHR of the ovary increased in HEP-treated hens (P < 0.05). In conclusion, dietary HEP supplementation exhibited potential hepatic and ovarian protective effects, thereby increasing the laying performance of aged hens by enhancing reproductive hormone secretion hormone secretion and promoting yolk precursor synthesis and follicle development via the liver-blood-ovary axis. The optimal supplementation level of HEP in aged hens was 500 mg/kg.