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Combinatorial Chemistry & High... Jun 2024The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are...
BACKGROUND
The occurrence of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is prevalent and perilous among older individuals. Inflammation and oxidative stress are vital factors in the progression of ALI in this population. Dayuan Yin (DYY) is a classic Chinese herbal formula used for treating pulmonary diseases. Therefore,this situation can be well simulated by selecting suitable aged rats and induced by LPS, which is helpful to evaluate the role of DYY.
OBJECTIVE
The objective of this study is to assess the therapeutic efficacy of DYY in reducing pulmonary inflammation and oxidative stress injury in aged rats induced by LPS.
METHODS
In elderly male Sprague Dawley (SD) rats, the ALI model was induced by injecting LPS into the peritoneal cavity. The therapeutic effect of the DYY group was evaluated after 3 days of oral administration. Lung tissue damage was assessed using hematoxylin-eosin staining and the lung wet/dry (W/D) ratio. Inflammatory reaction in lung tissue was analyzed by counting inflammatory agents, measuring total protein (TP), and examining the concentration of inflammatory components in bronchoalveolar lavage fluid (BALF). Lung oxidative stress was assessed by measuring malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and superoxide dismutase (SOD) levels in BALF. The impact of DYY on the phosphorylation of PI3K, AKT, and NF-κBp65 protein was analyzed using Western Blot (WB).
RESULTS
The administration of DYY exhibited a dose-dependent reduction in the severity of lung injury caused by LPS, leading to a reversal of the LPS-induced lung W/D ratio. Furthermore, DYY treatment resulted in decreased levels of leukocytes, eosinophils, neutrophils, macrophages, lymphocytes, and total protein in BALF. Additionally, DYY significantly inhibited the upregulation of Interleukin -6, Interleukin -10, and Interleukin -1β (IL-6, IL-10, IL-1β) as well as Tumor necrosis factor-α(TNF-α) induced by LPS (P<0.01). The lungs experienced oxidative stress due to LPS, leading to the production of MDA and iNOS, as well as a decrease in SOD activity. DYY reduced oxidative stress in the lungs and inhibited the activation of p-PI3K, p-Akt, and p-NF-κBp65, with a greater effect at higher doses.
CONCLUSION
In a dose-dependent manner, DYY suppresses the inflammatory response and oxidative stress in the lung tissue of elderly rats, thereby reducing ALI caused by LPS. This effect may be attributed to the inhibition of the PI3K/AKT/NF-κB pathway activation.
PubMed: 38920065
DOI: 10.2174/0113862073294620240527102409 -
Clinical Science (London, England :... Jul 2024Optimal vascular structure and function are essential for maintaining the physiological functions of the cardiovascular system. Vascular remodelling involves changes in... (Review)
Review
Optimal vascular structure and function are essential for maintaining the physiological functions of the cardiovascular system. Vascular remodelling involves changes in vessel structure, including its size, shape, cellular and molecular composition. These changes result from multiple risk factors and may be compensatory adaptations to sustain blood vessel function. They occur in diverse cardiovascular pathologies, from hypertension to heart failure and atherosclerosis. Dynamic changes in the endothelium, fibroblasts, smooth muscle cells, pericytes or other vascular wall cells underlie remodelling. In addition, immune cells, including macrophages and lymphocytes, may infiltrate vessels and initiate inflammatory signalling. They contribute to a dynamic interplay between cell proliferation, apoptosis, migration, inflammation, and extracellular matrix reorganisation, all critical mechanisms of vascular remodelling. Molecular pathways underlying these processes include growth factors (e.g., vascular endothelial growth factor and platelet-derived growth factor), inflammatory cytokines (e.g., interleukin-1β and tumour necrosis factor-α), reactive oxygen species, and signalling pathways, such as Rho/ROCK, MAPK, and TGF-β/Smad, related to nitric oxide and superoxide biology. MicroRNAs and long noncoding RNAs are crucial epigenetic regulators of gene expression in vascular remodelling. We evaluate these pathways for potential therapeutic targeting from a clinical translational perspective. In summary, vascular remodelling, a coordinated modification of vascular structure and function, is crucial in cardiovascular disease pathology.
Topics: Humans; Vascular Remodeling; Inflammation; Cardiovascular Diseases; Hypertension; Animals; Oxidative Stress; Signal Transduction; Oxidation-Reduction
PubMed: 38920058
DOI: 10.1042/CS20220797 -
Current Neuropharmacology Jun 2024Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing...
BACKGROUND
Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.
METHODS
An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls.
RESULTS
EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients.
CONCLUSION
EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.
PubMed: 38919004
DOI: 10.2174/1570159X22666240530095721 -
Current Pharmaceutical Biotechnology Jun 2024Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are...
INTRODUCTION
Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases.
METHOD
The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart.
RESULTS
It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status.
CONCLUSION
Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.
PubMed: 38918977
DOI: 10.2174/0113892010303097240605105013 -
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 -
Burns : Journal of the International... Jun 2024Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme...
INTRODUCTION
Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme plays an important role in cellular defense against oxidative stress such as burn injury. The aim of this study was to load SOD into solid lipid nanoparticles for the treatment of rat burn wounds.
METHODS
Solid lipid nanoparticles were prepared by Solvent Emulsification Diffusion method and evaluated for particle size, enzyme activity and enzyme entrapment efficiency. Twenty-seven rats in 3 different groups were induced with deep second-degree burns and then treated with SOD-loaded solid lipid nanoparticles, solid lipid nanoparticles without enzyme, or SOD solution. After the treatment period, the wounds were evaluated macroscopically for the area of healing and microscopically for indices of re-epithelialization, granulation tissue and angiogenesis.
RESULTS
The optimized SOD-loaded solid lipid nanoparticles showed a particle size of 35-85 ± 2.41 nm, 78.4 ± 4.31 % entrapment efficiency and 90 % initial enzyme activity. Macroscopic examination showed that the best recovery rate belonged to the solid lipid nanoparticle group. Pathological studies also showed that angiogenesis and granulation tissue were significantly better in this group. Compared to the other two groups, SOD-loaded solid lipid nanoparticles showed a significant improvement in pathological factors, particularly angiogenesis and granulation tissue, as well as a faster reduction in the number of inflammatory cells.
CONCLUSION
Based on this study, solid lipid nanoparticles could be used as an effective delivery system for SOD in the treatment of second-degree burns.
PubMed: 38918152
DOI: 10.1016/j.burns.2024.05.017 -
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 -
Analytical and Bioanalytical Chemistry Jun 2024Carbon-based nanozymes are synthetic nanomaterials that are predominantly constituted of carbon-based materials, which mimic the catalytic properties of natural enzymes,... (Review)
Review
Carbon-based nanozymes are synthetic nanomaterials that are predominantly constituted of carbon-based materials, which mimic the catalytic properties of natural enzymes, boasting features such as tunable catalytic activity, robust regenerative capacity, and exceptional stability. Due to the impressive enzymatic performance similar to various enzymes such as peroxidase, superoxide dismutase, and oxidase, they are widely used for detecting and degrading pollutants in the environment. This paper presents an exhaustive review of the fundamental design principles, catalytic mechanisms, and prospective applications of carbon-based nanozymes in the environmental field. These studies not only serve to augment the comprehension on the intricate operational mechanism inherent in these synthetic nanostructures, but also provide essential guidelines and illuminating perspectives for advancing their development and practical applications. Future studies that are imperative to delve into the untapped potential of carbon-based nanozymes within the environmental domain was needed to be explored to fully harness their ability to deliver broader and more impactful environmental preservation and management outcomes.
PubMed: 38916795
DOI: 10.1007/s00216-024-05405-7 -
Inflammopharmacology Jun 2024An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential...
An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1β, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1β, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.
PubMed: 38916711
DOI: 10.1007/s10787-024-01512-0