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Antibiotics (Basel, Switzerland) Jun 2024, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand...
, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect with antimicrobials against various infections. Here, we first found DC exerted a killing effect on planktonic and biofilm cells. Moreover, DC showed a synergistic effect with fluconazole (FLC) and amphotericin B (AMB). Notably, near-to-complete eradication of AMB-tolerant biofilm persisters was achieved upon DC treatment. Next, the mechanism of action of DC was explored through mapping the genes and proteomic profiles of DC-treated . The multi-omics analysis, quantitative real-time PCR and assay of reactive oxygen species (ROS) demonstrated DC exerted an antifungal effect on by increasing cellular oxidative stress. As revealed by multiple analyses (e.g., protein assay based on absorbance at 280 nm and rhodamine 6G assay), DC was able to enhance membrane permeability, inhibit drug efflux and increase cellular FLC/AMB concentration of , thereby mediating its synergism with the antifungals. Furthermore, DC inhibited superoxide dismutase 2 (SOD2) expression and manganese-containing SOD (Mn SOD) activity, leading to ROS production and enhanced killing of biofilm persisters. The current findings demonstrate that the adjunctive use of DC in combination with antifungals is a promising strategy for effective control of infections and management of antifungal resistance/tolerance in biofilms.
PubMed: 38927187
DOI: 10.3390/antibiotics13060521 -
BMC Plant Biology Jun 2024Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal...
Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61-65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na ions and concomitantly decreased the K and Ca absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.
Topics: Brassica napus; Salicylic Acid; Salt Stress; Chlorophyll; Plant Growth Regulators; Plant Leaves; Sodium Chloride; Antioxidants
PubMed: 38926637
DOI: 10.1186/s12870-024-05314-y -
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 -
Journal of Plant Physiology Jun 2024Seed inoculation with entomopathogenic fungi (EPF) causes plant-mediated effects against arthropod herbivores, but the responses vary among EPF isolates. We used a wheat...
Seed inoculation with entomopathogenic fungi (EPF) causes plant-mediated effects against arthropod herbivores, but the responses vary among EPF isolates. We used a wheat model system with three isolates representing Beauveria bassiana and Metarhizium spp. causing either negative or positive effects against the aphid Rhopalosiphum padi. Activities of six carbohydrate enzymes increased in plants showing biomass build-up after EPF inoculations. However, only aldolase activity showed positive correlation with R. padi numbers. Plants inoculated with M. robertsii hosted fewest aphids and showed increased activity of superoxide dismutase, implying a defense strategy of resistance towards herbivores. In M. brunneum-inoculated plants, hosting most R. padi, activities of catalase and glutathione reductase were increased suggesting enhanced detoxification responses towards aphids. However, M. brunneum simultaneously increased plant growth indicating that this isolate may cause the plant to tolerate herbivory. EPF seed inoculants may therefore mediate either tolerance or resistance towards biotic stress in plants in an isolate-dependent manner.
PubMed: 38924905
DOI: 10.1016/j.jplph.2024.154298 -
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