SOD2 Expression Research Articles

The formation of lamellar body-like structures may be a trigger of cetylpyridinium chloride-induced cell death and inflammatory response

Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 μg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately −6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death.

Heavy metals and elderly kidney health: A multidimensional study through Enviro-target Mendelian Randomization

Chronic Kidney Disease (CKD), closely linked to environmental factors, poses a significant public health challenge. This study, based on 529 triple-repeated measures from key national environmental pollution area and multiple gene-related public databases, employs various epidemiological and bioinformatics models to assess the impact of combined heavy metal exposure (Chromium [Cr], Cadmium [Cd], and Lead [Pb]) on early renal injury and CKD in the elderly. Introducing the novel Enviro-Target Mendelian Randomization method, our research explores the causal relationship between metals and CKD. The findings indicate a positive correlation between increased levels of metal and renal injury, with combined exposure caused renal damage more significantly than individual exposure. The study reveals that metals primarily influence CKD development through oxidative stress and metal ion resistance pathways, focusing on three related genes (SOD2, MPO, NQO1) and a transcription factor (NFE2L2). Metals were found to regulate oxidative stress levels in the body by increasing the expression of SOD2, MPO, NQO1, and decreasing NFE2L2, leading to CKD onset. Our research establishes a new causal inference framework linking environmental pollutants-pathways-genes-CKD, assessing the impact and mechanisms of metal exposure on CKD. Future studies with more extensive in vitro evidence and larger population are needed to validate.

Flaxseed Oil, Casitose, and Its Combination Diets Increase Antioxidant Activity and Upregulates Aging-related Genes in Drosophila melanogaster

Abstract Background: Nutrigenomics refers to the study of how diet influences the genomic expression and function of an organism. Diet is a significant factor that impacts metabolism, aging, and lifespan. Long-term dietary patterns can influence the risk of age-related diseases, including diabetes, cardiovascular diseases, hypertension, and cancer. While research in Drosophila melanogaster has focused on areas such as calorie restriction, high-sugar and high-fat diets, micronutrients, and disease-specific nutritional interventions, the effects of different combinations of macronutrients have not been adequately studied. This study aimed to analyze the impact of individual macronutrients, specifically flaxseed oil (a source of fat) and casitose (hydrolyzed milk protein), as well as their combinations, on longevity, antioxidant activity, and the expression of aging-related genes in D. melanogaster. Methods: The study examined the in vivo effects of different concentrations of flaxseed oil (120 μl, 240 μl, 480 μl, and 960 μl), casitose (125 mg, 250 mg, 500 mg, and 1000 mg), and their combinations with a base diet on longevity, antioxidant activity, and the expression of aging-related genes, namely manganese superoxide dismutase (Mn-SOD or SOD1) and copper–zinc SOD (Cu-Zn SOD or SOD2) in D. melanogaster. Results: The study found that flaxseed oil, casitose, and their combinations increased lipid peroxidation (LPO) activity, leading to the production of reactive oxygen species. However, these substances also enhanced the activity of the antioxidant enzymes SOD and catalase, which help combat-free radicals. Furthermore, the gene expression of SOD1 and SOD2 was upregulated, suggesting a potential mechanism for the observed improvements in lifespan. Interestingly, high doses of flaxseed oil (960 μl) were associated with decreased lifespan in the flies. Conclusion: The findings indicate that the optimal levels of flaxseed oil, casitose, or their combination can increase lifespan in Drosophila by upregulating the expression of the antioxidant enzymes SOD1 and SOD2. This provides insights into the potential of targeted nutrient combinations as a dietary approach to combat aging-related diseases.

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events.

Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK's ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1β and TNF-α, besides downregulation of NF-κB and IL-1β expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.

Therapeutic effects of Tanshinone IIA and Tetramethylpyrazine nanoemulsions on cognitive impairment and neuronal damage in Alzheimer's disease rat models.

The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer's disease (AD) rats. The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism. The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats. TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.

RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene lowering a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNASOD1 extended survival in SOD1-G93A ALS mice, surpassing survival previously seen in these mice by ASO modalities, slowed disease progression, and prevented ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.

Interaction Between Aging-Related Elastin-Derived Peptide (VGVAPG) and Sirtuin 2 and its Impact on Functions of Human Neuron Cells in an In Vitro Model.

Elastin is a stable protein present in many tissues, including brain tissues, and is one of the most long-life proteins with a half-life of approximately 70 years. The peptide with a Val-Gly-Val-Ala-Pro-Gly (VGVAPG) amino acid sequence is released during elastin decay, which correlates with aging-related neurodegeneration. A recent study has shown enhanced protein expression of Sirtuin 2 (SIRT2 - one of the redox homeostatic factors) in aged rodent brains, while the correlation between VGVAPG and SIRT2 has never been evaluated so far. Therefore, the study aimed to determine the impact of the VGVAPG hexapeptide on SIRT2 and neuronal functions in differentiated SH-SY5Y cells at the gene and protein expression levels. The present results showed that VGVAPG caused a 52.69% decrease in the level of reactive oxygen species (ROS), as in the case of neurons treated with AGK2 (Sirtuin 2 inhibitor) after 24h and 48h. Furthermore, a decrease in superoxide dismutase (SOD) activity was observed. The SIRT2 gene expression was found to fluctuate after 6h and 24h as a result of the exposure to the VGVAPG peptide. In turn, a decrease in the PPARγ, P53, SOD2, and CAT mRNA expression was shown in VGVAPG-treated cells. Additionally, an increase in the Sirtuin 2 protein expression was recorded after 24h and 48h in the VGVAPG peptide-treated neurons. Last but not least, the decrease in the level of acetylation of α-tubulin after the hexapeptide treatment was correlated with shortening of neurites, which may indicate the destabilization of the microtubule and ROS-independent induction of neurodegeneration.

Preclinical Effects Of Melatonin On The Development Of Ehrlich's Tumor: A Biochemical, Cognitive, And Molecular Approach.

It has already been shown that melatonin is an antitumoral molecule that affects malignant cells via some mechanisms. The benefit played by this hormone on cancer is due to its antioxidant effects. This study aimed to evaluate the preclinical effects of melatonin in mice with the Ehrlich ascites tumor. Twenty Balb/ c male mice with Ehrlich tumor were treated with different melatonin doses. Their inflammatory and oxidative stress were accessed by gene expression. Hepatotoxicity and hematological parameters were also evaluated through biochemical analyses. Animal welfare was analysed weekly from the categories guided by the NC3Rs. Gene expression analyses have shown that only Tnfα and Sod1 were expressed in all groups studied. Only the M-3 group showed increased Tnfα expression compared to the control. All groups treated with melatonin showed decreased Sod1 expression compared to the control. No signs of hepatotoxicity were caused by any of the melatonin doses used in the treatment. In animals with Ehrlich´s tumor treated with melatonin, a decrease in oxidative stress, an amelioration in welfare and in cognitive tasks could be observed, even if the treatment has not reduced the size of the tumor itself. In parallel with the already patented use of melatonin in the treatment of sleep disorders or chronic kidney disease, our results propose its use to improve the general well-being of breast cancer patients.

Screening and Mechanism Study of Three Antagonistic Drugs, Oxysophoridine, Rutin, and Phellodendrine, against Zearalenone-Induced Reproductive Toxicity in Ovine Oocytes.

Zearalenone (ZEN) is a common fungal toxin with reproductive toxicity in various grains. It poses a serious threat to ovine and other animal husbandry industries, as well as human reproductive health. Therefore, investigating the mechanism of toxicity and screening antagonistic drugs are of great importance. In this study, based on the natural compound library and previous Smart-seq2 results, antioxidant and anti-apoptotic drugs were selected for screening as potential antagonistic drugs. Three natural plant compounds (oxysophoridine, rutin, and phellodendrine) were screened for their ability to counteract the reproductive toxicity of ZEN on ovine oocytes in vitro using quantitative polymerase chain reaction (qPCR) and reactive oxygen species detection. The compounds exhibited varying pharmacological effects, notably impacting the expression of antioxidant (GPX, SOD1, and SOD2), autophagic (ATG3, ULK2, and LC3), and apoptotic (CAS3, CAS8, and CAS9) genes. Oxysophoridine promoted GPX, SOD1, ULK2, and LC3 expression, while inhibiting CAS3 and CAS8 expression. Rutin promoted SOD2 and ATG3 expression, and inhibited CAS3 and CAS9 expression. Phellodendrine promoted SOD2 and ATG3 expression, and inhibited CAS9 expression. However, all compounds promoted the expression of genes related to cell cycle, spindle checkpoint, oocyte maturation, and cumulus expansion factors. Although the three drugs had different regulatory mechanisms in enhancing antioxidant capacity, enhancing autophagy, and inhibiting cell apoptosis, they all maintained a stable intracellular environment and a normal cell cycle, promoted oocyte maturation and release of cumulus expansion factors, and, ultimately, counteracted ZEN reproductive toxicity to promote the in vitro maturation of ovine oocytes. This study identified three drugs that antagonize the reproductive toxicity of ZEN on ovine oocytes, and compared their mechanisms of action, providing data support and a theoretical basis for their subsequent application in the ovine breeding industry, reducing losses in the breeding industry, screening of ZEN reproductive toxicity antagonists and various toxin antagonists, improving the study of ZEN reproductive toxicity mechanisms, and even protection of human reproductive health.

PAR level mediates the link between ROS and inflammatory response in patients with type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (T2DM) is characterized by disrupted glucose homeostasis and metabolic abnormalities, with oxidative stress and inflammation playing pivotal roles in its pathophysiology. Poly(ADP-ribosyl)ation (PARylation) is a post-translational process involving the addition of ADP-ribose polymers (PAR) to target proteins. While preclinical studies have implicated PARylation in the interplay between oxidative stress and inflammation in T2DM, direct clinical evidence in humans remains limited. This study investigates the relationship between oxidative stress, PARylation, and inflammatory response in T2DM patients. MethodsThis cross-sectional investigation involved 61 T2DM patients and 48 controls. PAR levels were determined in peripheral blood cells (PBMC) by ELISA-based methodologies. Oxidative stress was assessed in plasma and PBMC. In plasma, we monitored reactive oxygen metabolites (d-ROMs) and ferric-reducing antioxidant power. In PBMC, we measured the expression of antioxidant enzymes SOD1, GPX1 and CAT by qPCR. Further, we evaluated the expression of inflammatory mediators such as IL6, TNF-α, CD68 and MCP1 by qPCR in PBMC. ResultsT2DM patients exhibited elevated PAR levels in PBMC and increased d-ROMs in plasma. Positive associations were found between PAR levels and d-ROMs, suggesting a link between oxidative stress and altered PAR metabolism. Mediation analysis revealed that d-ROMs mediate the association between HbA1c levels and PAR, indicating oxidative stress as a potential driver of increased PARylation in T2DM. Furthermore, elevated PAR levels were found to be associated with increased expression of pro-inflammatory cytokines IL6 and TNF-α in the PBMC of T2DM patients. ConclusionsThis study highlights that hyperactivation of PARylation is associated with poor glycemic control and the resultant oxidative stress in T2DM. The increase of PAR levels is correlated with the upregulation of key mediators of the inflammatory response. Further research is warranted to validate these findings and explore their clinical implications.

Integrated physiological, whole transcriptomic and functional analysis reveals the regulatory mechanism in the liver of rainbow trout (Oncorhynchus mykiss) in response to short-term and chronic hypoxia stress

The frequency of fish encountering hypoxia has risen dramatically as global warming and water pollution intensify, posing a serious threat to survival. Rainbow trout (Oncorhynchus mykiss), which is an economically important fish worldwide, belongs to a typical hypoxia-sensitive fish. However, little is known about the differences in response mechanisms employed by rainbow trout to short-term and chronic hypoxia stress and the roles of non-coding RNAs (ncRNAs) in the response of rainbow trout to hypoxia stress. In this study, we systematically analyzed the changes of liver biochemical parameters in rainbow trout exposed to moderate hypoxic conditions (DO: 4.5 ± 0.1 mg/L) for different durations (4, 8, 12, 24 h and 1 month) and 24 h reoxygenation, and histologic and transcriptome profiles (lncRNA, miRNA and mRNA) under hypoxia stress for 12 h (Tm12L) and 1 month (TmlL) compared with control (normoxia, DO: 8.5 ± 0.1 mg/L), and target and regulatory relationships between LOC110520201, miR-2188-y and superoxide dismutase 1 (sod1) were verified by dual-luciferase reporter, overexpression and silencing assays. Histological observations revealed that liver showed no pathological changes in TmlL. Integrating biochemical parameters and mRNA expression profiles, we found that exposure to short-term hypoxia stress resulted in enhanced immune response, aerobic and anaerobic glycolysis and lipid metabolism. In TmlL, increased anaerobic glycolysis and decreased aerobic glycolysis were observed, and antioxidant and immune capacity has returned to normal. Additionally, several key hypoxia-related genes (epo, vegfc, epor, sod1, ppara, foxo1a, gk, dusp1, nlrc3 and nlrp3) and ceRNA regulatory networks were identified from 2711 differentially expressed (DE) mRNAs, 575 DElncRNAs and 395 DEmiRNAs, including LOC110520201-miR-2188-y-sod1, LOC110533332-miR-144-y-vegfc, LOC110526066-miR-465-x-ppara and LOC110535032-miR-743-y-nlrp3. The analysis of expression patterns in rainbow trout liver and liver cells treated with hypoxia suggested that changes in LOC110520201, miR-2188-y and sod1 showed a ceRNA regulatory relationship. Further experiments demonstrated that sod1 was a target of miR-2188-y, and LOC110520201 silencing increased the expression of miR-2188-y and inhibited sod1 expression. These results facilitate our understanding of the molecular mechanisms of hypoxia response in rainbow trout and provide genetic resources for breeding hypoxia-tolerant varieties.

A trend over time study of hepatic Farnesoid-X-activated receptor and its downstream targets modulation by valproic acid in mice

Valproic acid (VA) is a broad-spectrum anticonvulsant agent that acts through several molecular mechanisms to control different types of seizures. The main concern of the drug is its liver toxicity. Considering the regulatory roles of the Farnesoid nuclear receptors and the nuclear transcription factor Nrf2 in modifying and neutralizing the harmful effects of oxidative damage, the present study was designed to evaluate the role of FXR-Nrf2 and some downstream target gene alterations in hepatotoxicity induced by VA. Thirty-five eight-week-old male albino mice were randomly divided into five groups, including a control group, and four groups were assigned to receive VA (300 mg/kg/day; oral) for 3, 7, 10, and 14 days. Serum levels of ALT, AST, ALP, and total and direct bilirubin (TB, DB) were measured. Liver histology and the expression of FXR, Nrf2, α-GST, SOD, and TNF-α were assessed using H&E staining and real-time RT-PCR techniques. Maximum extent of biochemical and histopathological damage was observed on the 14th day, but changes in the expression of FXR, Nrf2, α-GST, and SOD were seen at three points: a significant upregulation on the 3rd day, a remarkable downregulation on the 10th day, and a second-time upregulation on the 14th day. In conclusion, considering the observed dysregulation in FXR-Nrf2 cascade expression during VA administration, it seems that downregulation in this pathway and consequently its downstream detoxification and antioxidant genes may play a role in liver toxicity.

Jujubae Fructus extract prolongs lifespan and improves stress tolerance in Caenorhabditis elegans dependent on DAF-16/SOD-3

Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Manganese porphyrin-based treatment improves fetal-placental development and protects against oxidative damage and NLRP3 inflammasome activation in a rat maternal hypothyroidism model

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1β, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.

TGR5, GLP-1, and GIP expression in diabetic Wistar rats in response to Ficus exasperata vahl leaf extract

BackgroundDiabetes mellitus remains a critical global health issue, driving the need for continual exploration of new therapeutic strategies. Ficus exasperata Vahl, renowned for its extensive ethnomedicinal use, holds promise as a potential remedy for diabetes. However, its precise mechanisms of action in managing diabetes remain unclear. This study aimed to investigate the impact of Ficus exasperata Vahl leaf extract (MEFE) on the expression of TGR5, GLP-1, and GIP in diabetic Wistar rats. MethodUsing methanol extraction, Ficus exasperata was processed and characterized through GC–MS analysis. Twenty rats were divided into four groups: diabetic untreated, normal control, diabetes treated with MEFE (200 mg/kg), and diabetes treated with insulin (0.3 units). Diabetes induction utilized alloxan monohydrate (150 mg/kg, intraperitoneal), followed by daily treatments for 28 days. Blood glucose and insulin levels were assessed via glucose oxidase and ELISA, while antioxidant enzyme activities (SOD, catalase, GPx) and total protein were measured using randox kits. Gene expression of GLP-1, TGR5, and GIP was quantified through qPCR. In silico docking of MEFE compounds to the P2Y1 receptor was conducted using Cavity-detection guided blind-docking software. Pancreatic islet histology was examined with hematoxylin and eosin stains, and statistical significance was determined with GraphPad Prism (p < 0.05). ResultThe GC–MS analysis identified 23 constituents in MEFE, with kaur-16-ene exhibiting the highest binding affinity (-8.2 Kcal) against the P2Y1 receptor. Significant reductions in blood glucose levels were observed in the MEFE-treated diabetic group, accompanied by increased expression of insulin, TGR5, GLP-1, GIP, SOD, catalase, and GPx compared to the untreated diabetic group. Additionally, MEFE treatment facilitated the regeneration of pancreatic islet cells. ConclusionThese findings suggest that MEFE exerts antioxidative effects and stimulates genes crucial for controlling blood glucose levels in diabetic rats.

Environmental and Sublethal Concentrations of Polystyrene Nanoplastics Induced Antioxidant System, Transcriptomic Responses, and Disturbed Gut Microbiota in Oyster Magallana Hongkongensis.

Nanoplastics (NPs) are emerging contaminants having persistent nature, diverse ecological impacts, and potential food safety risks. Here, we examined the ecotoxicity of 80 nm polystyrene nanoplastics (PS-NPs) at environmentally relevant concentrations (ERCs, 10 and 100 μg/L), and sublethal concentrations (SLCs, 500 and 2500 μg/L) in Magallana hongkongensis. Results showed that SLCs significantly (p < 0.05) increased superoxide dismutase (SOD), catalase (CAT), and alkaline phosphatase (AKP) activities and altered tnfα, cat, gst, sod, and se-gpx genetic expressions. Further, PS-NP exposure at both levels reduced beneficial bacteria and increased potentially pathogenic bacteria in the gut. In transcriptomic analysis, 5118 and 4180 differentially expressed genes (DEGs) were identified at ERCs, while 5665 and 4817 DEGs were found at SLCs, respectively. Upregulated DEGs enriched lysosomes, ABC transporters, and apoptosis pathways, while downregulated DEGs enriched ribosomal pathways. Overall, ERCs significantly altered gut microbiota and transcriptomic responses, while SLCs, in addition, also impacted the antioxidant and immune systems.

Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging.

Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO2 peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins SOD2, TRX2, PRX3, PRX5, and GRX2 were associated with higher levels of mitochondrial respiration and VO2 peak. In addition, greater SOD2, PRX3, and GRX2 expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.

Alpha terpineol preconditioning enhances regenerative potential of mesenchymal stem cells in full thickness acid burn wounds

Regeneration of full thickness burn wounds is a significant clinical challenge. Direct stem cell transplantation at the wound site has a promising effect on wound regeneration. However, stem cell survival within the harsh wound environment is critically compromised. In this regard, preconditioning of stem cells with cytoprotective compounds can improve the efficiency of transplanted cells. This study evaluated the possible effect of alpha terpineol (αT) preconditioned mesenchymal stem cells (αT-MSCs) in full thickness acid burn wound. An optimized concentration of 10 μM αT was used for MSC preconditioning, followed by scratch assay analysis. A novel rat model of full thickness acid burn wound was developed and characterized via macroscopic and histological examinations. Treatment (normal and αT-MSCs) was given after 48 h of burn wound induction, and the healing pattern was examined till day 40. Skin tissues were harvested at the early (day 10) and late (day 40) wound healing phases and examined by histological grading, neovascularization, and gene expression profiling of healing mediators. In scratch assay, αT-MSCs exhibited enhanced cell migration and wound closure (scratch gap) compared to normal MSCs. In vivo findings revealed enhanced regeneration in the wound treated with αT-MSCs compared to normal MSCs and untreated control. Histology revealed enhanced collagen deposition with regenerated skin layers in normal MSC- and αT-MSC treated groups compared to the untreated control. These findings were correlated with enhanced expression of α-SMA as shown by immunohistochemistry. Additionally, αT-MSC group showed reduced inflammation and oxidative stress, and enhanced regeneration, as witnessed by a decrease in IL-1β, IL-6, TNF-α, and Bax and an increase in BCL-2, PRDX-4, GPX-7,SOD-1, VEGF, EGF, FGF, MMP-9, PDGF, and TGF-β gene expression levels at early and late phases, respectively. Overall findings demonstrated that αT exerts its therapeutic effect by mitigating excessive inflammation and oxidative stress while concurrently enhancing neovascularization. Thus, this study offers new perspectives on managing full thickness acid burn wounds in future clinical settings.

Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans.

Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

Overexpression of Extracellular Superoxide Dismutase 3 Inhibits Cancer Cell Growth and Migration in Colorectal Cancer.

Incidence of colorectal cancer is rapidly increasing worldwide. Extracellular superoxide dismutase (EcSOD; SOD3) is an antioxidant enzyme. However, SOD3 roles in colorectal cancer progression remain uncertain. Superoxide dismutase 3 expression was evaluated, and we analyzed clinical relevance of SOD3 expression in colorectal cancer. Subsequently, SOD3 roles in colorectal cancer progression were detected by gain of function experiments. Changes in subcutaneous tumor and liver nodule size after SOD3 overexpression were examined in nude mice. The expression of proliferation marker Ki67 was assessed by immunohistochemical staining. Supperoxide dismutase 3 was downregulated in colorectal cancer (P <.01). Downregulation of SOD3 was correlated with unfavorable outcomes (P < .05). Superoxide dismutase 3 upregulation limited the proliferative (P <.05), migrative (P <.01) and invasive actions of colorectal cancer cells (P <.01) by suppressing epithelial-mesenchymal transition. Moreover, SOD3 overexpression reduced Ki67 expression (P <.01) and blocked tumor growth (P <01) and liver metastasis (P <.001) in mouse tumor model. Superoxide dismutase 3 upregulation attenuates tumor growth and liver metastasis in colorectal cancer, suggesting that SOD3 has potential diagnostic and prognostic values regarding colorectal cancer treatment.