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Scientific Reports Jun 2024Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage...
Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage to different organs. Although there has been progress in the identification and controlling of clinical sepsis, the fatality rates are still significant. This study, for the first time, intended to examine the possible ameliorative impact of Nebivolol, a β1-adrenergic antagonist antihypertensive drug, against nephrotoxicity resulted from cecal ligation and puncture (CLP)-induced sepsis in rats, on molecular basis. Sixty male Wistar albino rats were chosen. Oxidative stress indicators and biochemical markers of kidney activity were evaluated. Inflammatory mediators, fibrosis- and apoptosis-related proteins and gene expressions were investigated. Moreover, renal histopathological investigation was performed. CLP-induced nephrotoxicity characterized by markedly elevated serum levels of creatinine, blood urea nitrogen, uric acid, and renal malondialdhyde. On the other hand, it decreased serum total protein level, renal superoxide dismutase activity and reduced glutathione level. Additionally, it significantly elevated the renal inflammatory mediators (tumor necrosis factor-alpha, ilnerlukin (IL)-6, and IL-1β) and Caspase-3 protein, reduced IL-10 level, amplified the expression of transforming growth factor-beta 1 (TGF-β1), p-Smad2/3 and alpha-smooth-muscle actin proteins, downregulated the B cell lymphoma-2 (Bcl-2) gene and elevated the transcription of Bcl-2-associated X-protein (Bax), p53 and Nuclear factor-kappa B (NF-κB) genes. Furtheremor, kidney tissues exhibited significant histopathological changes with CLP. On the contrary, Nebivolol significantly improved all these biochemical changes and enhanced the histopathological alterations obtained by CLP. This research showed, for the first time, that Nebivolol effectively mitigated the CLP-induced kidney dysfunction via its antioxidant, antifibrotic and anti-apoptotic activity through modulation of oxidative stress, TGF-β/NF-κB and TGF-β/Smad/p53 signaling pathways.
Topics: Animals; Oxidative Stress; Nebivolol; Tumor Suppressor Protein p53; Rats; Male; Sepsis; Signal Transduction; Rats, Wistar; Smad Proteins; Kidney; Transforming Growth Factor beta; Apoptosis; Transforming Growth Factor beta1; Kidney Diseases
PubMed: 38926458
DOI: 10.1038/s41598-024-64577-5 -
PloS One 2024Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic...
Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam leaf extract prevents assault of streptozotocin on liver cells via inhibition of oxidative stress and activation of the NrF2/Keap1, PPARγ, and PTP1B signaling pathways.
BACKGROUND
Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries.
PURPOSE
The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways.
METHODS
A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined.
RESULTS
MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats.
CONCLUSION
It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM.
Topics: Animals; NF-E2-Related Factor 2; Male; Plant Extracts; Kelch-Like ECH-Associated Protein 1; Oxidative Stress; Plant Leaves; Signal Transduction; Rats; Rats, Wistar; Diabetes Mellitus, Experimental; PPAR gamma; Liver; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Asteraceae; Streptozocin; Hypoglycemic Agents
PubMed: 38924022
DOI: 10.1371/journal.pone.0306039 -
Toxins May 2024The aim of this study was to investigate the effects of aflatoxin B (AFB) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old...
The aim of this study was to investigate the effects of aflatoxin B (AFB) on cholestasis in duck liver and its nutritional regulation. Three hundred sixty 1-day-old ducks were randomly divided into six groups and fed for 4 weeks. The control group was fed a basic diet, while the experimental group diet contained 90 μg/kg of AFB. Cholestyramine, atorvastatin calcium, taurine, and emodin were added to the diets of four experimental groups. The results show that in the AFB group, the growth properties, total bile acid (TBA) serum levels and total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) liver levels decreased, while the malondialdehyde (MDA) and TBA liver levels increased ( < 0.05). Moreover, AFB caused cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin could reduce the TBA serum and liver levels ( < 0.05), alleviating the symptoms of cholestasis. The qPCR results show that AFB upregulated () and () gene expression and downregulated () gene expression in the liver, and taurine and emodin downregulated and gene expression ( < 0.05). In summary, AFB negatively affects health and alters the expression of genes related to liver bile acid metabolism, leading to cholestasis. Cholestyramine, atorvastatin calcium, taurine, and emodin can alleviate AFB-induced cholestasis.
Topics: Animals; Aflatoxin B1; Ducks; Cholestasis; Liver; Bile Acids and Salts; Poultry Diseases; Cholestyramine Resin; Animal Feed
PubMed: 38922135
DOI: 10.3390/toxins16060239 -
Toxics Jun 2024This study utilizes (MI) for the first time to investigate the uptake and translocation of chlorpyrifos (CPF; 10 µg g) from soil, introducing a new approach to improve...
This study utilizes (MI) for the first time to investigate the uptake and translocation of chlorpyrifos (CPF; 10 µg g) from soil, introducing a new approach to improve the efficacy of this technique, which includes using biosurfactants ( and ) at 10 CFU/mL to degrade CPF under greenhouse conditions. Moreover, antioxidant enzymes, including superoxide dismutase (SOD) and peroxidase (Prx), and oxidative stress due to hydrogen peroxide (HO) and malondialdehyde (MDA) in MI roots and leaves were evaluated under CPF stress. Our results demonstrated that amending soil with MI and followed by significantly reduced CPF levels in the soil ( > 0.05) and enhanced CPF concentrations in MI roots and leaves after 1, 3, 7, 10, and 14 days of the experiment. Furthermore, CPF showed its longest half-life (t) in soil contaminated solely with CPF, lasting 15.36 days. Conversely, its shortest half-life occurred in soil contaminated with CPF and treated with MI along with , lasting 4.65 days. Soil contaminated with CPF and treated with MI and showed a half-life of 7.98 days. The half-life (t) of CPF-contaminated soil with MI alone was 11.41 days. A batch equilibrium technique showed that is better than for eliminating CPF from soil in In vitro experiments. Notably, CPF-polluted soil treated with coadministration of MI and the tested bacteria improved the activities of SOD and Prx and reduced HO and MDA compared with CPF-polluted soil treated with MI alone. Our findings demonstrated that using and as biosurfactants to augment phytoremediation represents a commendable strategy for enhancing the remediation of CPF contamination in affected sites while reducing the existence of harmful pesticide remnants in crop plants.
PubMed: 38922115
DOI: 10.3390/toxics12060435 -
Pathogens (Basel, Switzerland) Jun 2024The sole known heme enzyme of the parasitic protist is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free...
The sole known heme enzyme of the parasitic protist is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome reductase activities and compared these to the activities of the flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s) is about two-thirds of that of Hmp (34 s) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with = 10 μM and 0.27 μM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it.
PubMed: 38921778
DOI: 10.3390/pathogens13060480 -
Journal of Nanobiotechnology Jun 2024Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2...
INTRODUCTION
Breast cancer ranks second as the most common malignancy globally, after lung cancer. Among the various subtypes of breast cancer, HER2 positive breast cancer (HER2 BC)poses a particularly challenging prognosis due to its heightened invasiveness and metastatic potential. The objective of this study was to construct a composite piezoelectric nanoparticle based on poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for imaging and treatment of HER2 BC.
METHOD
By reshaping the crystal structure of P(VDF-TrFE) piezoelectric nanoparticles, improving hydrophilicity, and incorporating imaging capabilities, we developed piezoelectric composite nanoparticles (PGd@tNBs) that integrate imaging and therapeutic functions. The in vitro characterization encompassed the assessment of piezoelectric properties, hydrophilicity, imaging performance, and therapeutic efficacy of these particles. The targeting and therapeutic effectiveness of PGd@tNBs particles were further validated in the SK-BR3 cell line and subsequently confirmed in HER2-positive tumor-bearing mice.
RESULTS
The nanoparticle demonstrated excellent biocompatibility and impressive multimodal imaging performance. Magnetic resonance imaging (MRI) observations revealed significant accumulation of PGd@tNBs particles in the HER2 positive tumor, exhibiting superior contrast-enhanced ultrasound performance compared to traditional ultrasound contrast agents, and small animal in vivo imaging showed that PGd@tNBs particles were primarily excreted through respiration and urinary metabolism. Piezoforce Microscopy characterization highlighted the outstanding piezoelectric properties of PGd@tNBs particles. Upon targeted binding to HER2-BC, ultrasound stimulation influenced the cell membrane potential, leading to reversible electroporation. This, in turn, affected the balance of calcium ions inside and outside the cells and the mitochondrial membrane potential. Following ingestion by cells, PGd@tNBs, when exposed to ultrasound, triggered the generation of reactive oxygen species (ROS), resulting in the consumption of glutathione and superoxide dismutase and achieving sonodynamic therapy. Notably, repeated ultrasound stimulation, post PGd@tNBs particles binding and entry into cells, increased ROS production and elevated the apoptosis rate by approximately 45%.
CONCLUSION
In conclusion, the PGd@tNBs particles developed exhibit outstanding imaging and therapeutic efficacy, holding potential for precise diagnosis and personalized treatment of HER2 BC.
Topics: Animals; Female; Breast Neoplasms; Humans; Mice; Cell Line, Tumor; Receptor, ErbB-2; Nanoparticles; Magnetic Resonance Imaging; Ultrasonic Therapy; Mice, Nude; Mice, Inbred BALB C; Contrast Media; Apoptosis
PubMed: 38918812
DOI: 10.1186/s12951-024-02639-6 -
BMC Plant Biology Jun 2024Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to...
BACKGROUND
Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network.
RESULTS
Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (HO) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB.
CONCLUSIONS
The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.
Topics: Plant Diseases; Melatonin; Disease Resistance; Fusarium; Vigna; Gene Regulatory Networks; Gene Expression Regulation, Plant; Salicylic Acid
PubMed: 38918732
DOI: 10.1186/s12870-024-05289-w -
PloS One 2024Increases in near-surface ozone (O3) concentrations is a global environmental problem. High-concentration O3 induces stress in plants, which can lead to visible damage... (Meta-Analysis)
Meta-Analysis
Increases in near-surface ozone (O3) concentrations is a global environmental problem. High-concentration O3 induces stress in plants, which can lead to visible damage to plants, reduced photosynthesis, accelerated aging, inhibited growth, and can even plant death. However, its impact has not been comprehensively evaluated because of the response differences between individual plant species, environmental O3 concentration, and duration of O3 stress in plants. We used a meta-analysis approach based on 31 studies 343 observations) to examine the effects of elevated O3 on malondialdehyde (MDA), superoxide dismutase (SOD), and peroxidase (POD) activities in herbaceous plants. Globally, important as they constitute the majority of the world's food crops. We partitioned the variation in effect size found in the meta-analysis according to the presence of plant species (ornamental herb, rice, and wheat), O3 concentration, and duration of O3 stress in plants. Our results showed that the effects of elevated O3 on plant membrane lipid peroxidation depending on plant species, O3 concentration, and duration of O3 stress in plants. The wheat SOD and POD activity was significantly lower compared to the herbs and rice (P<0.01). The SOD activity of all herbaceous plants increased by 34.6%, 10.5%, and 26.3% for exposure times to elevated O3 environments of 1-12, 13-30, and 31-60 days, respectively. When the exposure time was more than 60 days, SOD activity did not increase but significantly decreased by 12.1%. However, the POD activity of herbaceous plants increased by 30.4%, 57.3%, 21.9% and 5.81%, respectively, when exposure time of herbaceous plants in elevated O3 environment was 1-12, 13-30, 31-60 and more than 60 days. Our meta-analysis revealed that (1) rice is more resistant to elevated O3 than wheat and ornamental herbs likely because of the higher activity of antioxidant components (e.g., POD) in the symplasts, (2) exposure to elevated O3 concentrations for >60 days, may result in antioxidant SOD lose its regulatory ability, and the antioxidant component POD in the symplast is mainly used to resist O3 damage, and (3) the important factors affected the activity of SOD and POD in plants were not consistent: the duration of O3 stress in plants was more important than plant species and O3 concentration for SOD activity. However, for POD activity, plant species was the most important factor.
Topics: Superoxide Dismutase; Antioxidants; Ozone; Malondialdehyde; Lipid Peroxidation; Plants; Oxidative Stress; Oxidoreductases; Oryza; Peroxidase
PubMed: 38917096
DOI: 10.1371/journal.pone.0305688 -
Frontiers in Plant Science 2024The tolerance to salinity stress is an intricate phenomenon at cellular and whole plant level that requires the knowledge of contributing physiological and biochemical...
The tolerance to salinity stress is an intricate phenomenon at cellular and whole plant level that requires the knowledge of contributing physiological and biochemical processes and the genetic control of participating traits. In this context, present study was conducted with objective to evaluate the physiological, biochemical, and genetic responses of different wheat genotypes including bread wheat (BW) and synthetic hexaploids (SHs) under saline and control environment. The experiment was conducted in two factorial arrangement in randomized complete block design (RCBD), with genotypes as one factor and treatments as another factor. A significant decline in physiological traits (chlorophyll, photosynthesis, stomatal conductance, transpiration, and cell membrane stability) was observed in all genotypes due to salt stress; however, this decline was higher in BW genotypes as compared to four SH genotypes. In addition, the biochemical traits including enzymes [superoxide dismutase, catalase, and peroxidase (POD)] activity, proline, and glycine betaine (GB) illustrated significant increase along with increase in the expression of corresponding genes (, , , , and ) due to salt stress in SHs as compared to BW. Correspondingly, highly overexpressed genes, , , and caused a significant decline in Na/K in SH as compared to BW genotypes under salt stress. Moreover, correlation analysis, principal component analysis (PCA), and heatmap analysis have further confirmed that the association and expression of physiological and biochemical traits varied significantly with salinity stress and type of genotype. Overall, the physiological, biochemical, and genetic evaluation proved SHs as the most useful stock for transferring salinity tolerance to other superior BW cultivars via the right breeding program.
PubMed: 38916034
DOI: 10.3389/fpls.2024.1336571 -
Frontiers in Plant Science 2024Rapid industrialization and urbanization have caused severe soil contamination with cadmium (Cd) necessitating effective remediation strategies. Phytoremediation is a...
Rapid industrialization and urbanization have caused severe soil contamination with cadmium (Cd) necessitating effective remediation strategies. Phytoremediation is a widely adopted technology for remediating Cd-contaminated soil. Previous studies have shown that has a high Cd accumulation capacity and tolerance indicating its potential for Cd soil remediation. However, the mechanisms underlying its response to Cd stress remain unclear. In this study, physiological, transcriptomic, and metabolomic analyses were conducted to explore the response of roots to Cd stress at different time points. The results revealed that Cd stress significantly increased malondialdehyde (MDA) levels in , which simultaneously activated its antioxidant defense system, enhancing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) by 19.73%-50%, 22.87%-38.89%, and 32.31%-45.40% at 12 h, 36 h, 72 h, and 7 days, respectively, compared with those in the control (CK). Moreover, transcriptomic and metabolomic analyses revealed 245, 5,708, 9,834, and 2,323 differentially expressed genes (DEGs), along with 66, 62, 156, and 90 differentially expressed metabolites (DEMs) at 12 h, 36 h, 72 h, and 7 days, respectively. Through weighted gene coexpression network analysis (WGCNA) of physiological indicators and transcript expression, eight hub genes involved in phenylpropanoid biosynthesis, signal transduction, and metal transport were identified. In addition, integrative analyses of metabolomic and transcriptomic data highlighted the activation of lipid metabolism and phenylpropanoid biosynthesis pathways under Cd stress suggesting that these pathways play crucial roles in the detoxification process and in enhancing Cd tolerance in . This comprehensive study provides detailed insights into the response mechanisms of to Cd toxicity.
PubMed: 38916029
DOI: 10.3389/fpls.2024.1389207