Oxidative Stress Alterations Research Articles

Biogenic synthesis of ferric nanoparticles of Phyllanthus emblica exhibited breast cancer effect via alteration of mTOR/Maf-1/PTEN signaling pathway

Breast cancer is a major cause of mortality in females worldwide. Chemotherapeutic effects via utilizing natural, edible or synthetic drugs gaining an attention now a days and best approach against Breast cancer. In this experimental study, we fabricated the ferric oxide nanoparticles of Phyllanthus emblica extract (PEFeNPs) and scrutinized against 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary cancer in rodents and explore the possible underlying mechanism. Ferric nanoparticle of Phyllanthus emblica were synthesized, characterized using different spectroscopy method and its efficacy were tested against tumour bearing rats. Different biochemical parameter such as antioxidant profile, proinflammatory cytokines, biotransformation enzymes, gene expression, mitochondrial parameter, glycoprotein were analyzed in the serum or breast tissue. Histology study was performed to determine the reduction in the mammary tissue architecture. Fabricated PEFeNPs showed well defined structure and presence of iron in EDX. Rats treated with PEFeNPs exhibited improved body weight and alteration in organ weight. PEFeNPs significantly (P < 0.001) altered the antioxidant, glycoprotein, mitochondrial, inflammatory cytokines, hematological and biotransformation enzymes. It also altered the mRNA expression of Pi3K, phospho mTOR, phospho AKT, Liver X receptor alpha (LXRα), Liver X receptor beta (LXRβ) and Maf1. Histopathological study also supported the potential anticancer activity of PEFeNPs with well-organized tissue architecture. In short, the results of present research suggested the chemopreventive effect of iron oxide nanoparticles against the DMBA induced mammary cancer via alteration of oxidative stress and inflammatory reaction.

Oxidative Stress, Ferroptosis Indicators, and Nicorandil Efficacy in STEMI Patients During Percutaneous Coronary Intervention.

Myocardial ischemia-reperfusion injury (MI/RI) poses a significant challenge during coronary revascularization. This research investigated alterations in oxidative stress and ferroptosis, alongside the impact of nicorandil on these aspects, among patients undergoing acute ST-elevation myocardial infarction (STEMI) and receiving primary percutaneous coronary intervention (pPCI). 121 patients with STEMI who were undergoing pPCI were included in the study, and we documented their thrombolysis in myocardial infarction (TIMI) blood flow grades before and after the procedure. The serum levels of creatine kinase-MB, creatinine, and N-terminal prohormone of brain natriuretic peptide (NTpro-BNP) were assessed. Additionally, we analyzed serum levels of SIRT1, HIF-1α, GPX-4, FTH1, FSP1, 4-HNE, and SI before pPCI and 6 h post-pPCI. Follow-ups were conducted 12 weeks after discharge, with major adverse cardiovascular events (MACEs) documented. The nicorandil group showed significantly improved TIMI blood flow grades and lower CK-MB and NTpro-BNP levels at 24, 48, and 72 h after PCI. Although preoperative SIRT1, HIF-1α, and ferroptosis-related indicators were similar, post-PCI, SIRT1 increased less and HIF-1α increased more in the nicorandil group. The nicorandil group exhibited higher GPX4, FTH1, and FSP1 levels, and lower levels of 4-HNE and SI. While no significant differences in left ventricular function were observed, the nicorandil group had lower LVEDD at 12 weeks. Importantly, the incidence of unstable angina and heart failure was significantly lower in the nicorandil group. Administering nicorandil perioperatively during pPCI alleviates MI/RI, preserves cardiac and renal function, and reduces unstable anginarisk at 12 weeks post-PCI. These benefits of nicorandil may be attributed to its anti-oxidative stress and anti-ferroptosis effects.

Effect of Tetrahydrocurcumin Improves Erythromycin Estolate Induced Alterations of Acetylcholinesterase, ATPases and Oxidative Stress in Brain of Rats

Effect of Tetrahydrocurcumin Improves Erythromycin Estolate Induced Alterations of Acetylcholinesterase, ATPases and Oxidative Stress in Brain of Rats

Influence of consumption of the food additive carrageenan on the gut microbiota and the intestinal homeostasis of mice.

The safety of the carrageenan (CGN) consumption as a food additive is under debate, with negative effects being associated with the products of hydrolysis of CGN. Moreover, there is an increasing need to integrate gut microbiome analysis in the scientific risk assessment of food additives. The objective of this study was to test the effects of CGN consumption on the gut microbiota and the intestinal homeostasis of young male and female mice. Female and male ICR-CD1 mice (8 weeks old) orally received 540 mg kg-1 day-1 of CGN, representing the maximum-level exposure assessment scenario surveyed for children, over the course of two weeks. Fecal material and peritoneal immune cells were analyzed to determine changes in the fecal microbiota, based on the analysis of bacterial 16S rRNA gene amplicon sequences and short-chain fatty acid (SCFA) concentrations, and some immune functions and redox parameters of peritoneal leukocytes. Non-significant microbiota taxonomical changes associated with CGN intake were found in the mouse stools, resulting the housing time in an increase in bacterial groups belonging to the Bacteroidota phylum. The PICRUSt2 functional predictions showed an overall increase in functional clusters of orthologous genes (COGs) involved in carbohydrate transport and metabolism. A significant increase in the cytotoxicity of fecal supernatants was observed in CGN-fed mice, which correlated with worsening of immune functions and oxidative parameters. The altered immunity and oxidative stress observed in young mice after the consumption of CGN, along with the fecal cytotoxicity shown towards intestinal epithelial cells, may be associated with the gut microbiota's capacity to degrade CGN. The characterization of the gut microbiota's ability to hydrolyze CGN should be included in the risk assessment of this food additive.

Graded Effects of Dry-Feed Added Sodium Benzoate/Ascorbic Acid Combination on Neurobehaviour, Oxidative Stress, and Markers of Inflammation in Mice

Background: Several concerns regarding the safety of sodium benzoate/ascorbic acid combination have been highlighted in various scientific investigations. However, there is a dearth of scientific literature on its effect on the brain. This study investigated the effects of dry-feed added sodium benzoate/ascorbic acid combination on neurobehaviour, oxidative stress, and inflammatory cytokines in mice Methods: Adult male mice were assigned into ten groups of 10 mice each. One group was fed a standard diet, three groups were fed a diet containing sodium benzoate (NaB) at 125 mg/kg with ascorbic acid (AA) at 100, 200, or 300 mg/kg of feed, another three groups were fed NaB at 250 mg/kg with AA at 100, 200, or 300 mg/kg of feed, respectively, and the last three groups were fed NaB at 500 mg/kg with AA at 100, 200 or 300 mg/kg, respectively. Behavioural tests were assessed, following which animals were sacrificed, and their brains were homogenised for the assessment of biochemical parameters. Results: The result showed a decrease in body weight, self-grooming, total antioxidant capacity, inflammatory cytokines, mixed response with food intake, locomotor activity, Y maze spatial working memory, and anxiety-related behaviours and an increase in rearing and radial arm maze spatial working memory. Conclusion: Dry-feed added NaB/AA altered behavioural, oxidative stress, and inflammatory markers in mice. It was found that both beneficial and deleterious effects might be possible, depending on the concentrations ingested in food. However, further investigations are required to ascertain its effects on humans.

Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease

Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD. To address this hypothesis, the levels of 4-hydroxynonenal (4-HNE; i.e. a marker of oxidative stress damage) along with the protein expression and enzymatic activity of PON1 and PON2 have been investigated in the brain and serum of young [Postnatal day (PD)8–10, 20–25 and 60–65] asymptomatic 3xTg-AD female mice, one of the most used transgenic models of AD.At PD 8–10, there were no differences in hippocampus and prefrontal cortex (PFC) 4-HNE expression levels between 3xTg-AD mice compared to controls (Non-Tg mice). On the other hand, significant increased levels of 4-HNE were detected in PD 20–30 3xTg-AD mice hippocampus, while a significant reduction was observed in 3xTg-AD group at PD 60–65. In the PFC, 4-HNE levels were significantly reduced in 3xTg-AD mice brain at PD 20–30, while no differences in 4-HNE levels were detected at PD 60–65.No significant differences in arylesterase and lactonase activities were observed in the plasma of 3xTg-AD and Non-Tg mice at the different considered ages. Compared to Non-Tg mice, a reduction of brain arylesterase activity was found in 3xTg-AD female at PD 20–30 and PD 60–65, but it was significant only in the younger group. Finally, a similar trend was observed also for PON1 and PON2 protein levels, with both significantly, and solely, decreased in 3xTg-AD mice brain at PD 20–30.Overall, these findings suggest that the altered oxidative stress homeostasis in the 3xTg-AD female mice may be related to an early reduction in activity and expression of PONs enzymes most likely via a reduced brain arylesterases activity.

Identification and functional study of AA11 family polysaccharide monooxygenase genes in filamentous fungus Podospora anserina.

The lytic polysaccharide monooxygenase (LPMO) in the auxiliary active protein family (AA family) catalyzes the oxidative depolymerization of various refractory carbohydrates including cellulose, chitin and starch. While accumulating studies investigate the enzymology of LPMO, the research on the inactivation of LPMO genes has been rarely explored. In this study, five LPMO genes PaLPMO11A (Pa_4_4790), PaLPMO11B (Pa_1_5310), PaLPMO11C (Pa_2_7840), PaLPMO11D (Pa_2_8610) and PaLPMO11E (Pa_3_9420) of the AA11 family in the filamentous fungus Podospora anserina were knocked out by homologous recombination. Single mutants ΔPaLPMO11A (ΔA), ΔPaLPMO11B (ΔB), ΔPaLPMO11C (ΔC), ΔPaLPMO11D (ΔD) and ΔPaLPMO11E (ΔE) were constructed, and then all polygenic mutants were constructed via genetic crosses. The differences in the growth rate and sexual reproduction between wild type and mutant strains were observed on different carbon source media. The alteration of oxidative stress and cellulose degradation ability were found on DAB and NBT staining and cellulase activity determination. These results implicated that LPMO11 genes play a key role in the growth, development, and lignocellulose degradation of P. anserina. The results showed that the spore germination efficiency, growth rate and reproductive capacity of mutant strains including ΔBΔCΔE, ΔAΔBΔCΔE, ΔAΔCΔDΔE and ΔAΔBΔCΔDΔE was significantly decreased on different cellulose carbon sources and the remaining strains have no difference. The reduced utilization of various carbon sources, the growth rate, the spore germination rate, the number of fruiting bodies, the normal fruiting bodies, the shortened life span and the ability to degrade cellulose were found in strains which all five genes in the PaLPMO11 family were deleted. However, the strain still had 45% cellulase activity compared to wild type. These results suggest that LPMO11 genes may be involved in the growth and development, sexual reproduction, senescence and cellulose degradation of P. anserina. This study provides information for systematically elucidating the regulatory mechanism of lignocellulose degradation in filamentous fungus P. anserina.

The Uses of Anabolic Androgenic Steroids Among Athletes; Its Positive and Negative Aspects- A Literature Review.

The use of anabolic androgenic steroids (AAS) for strength training and muscle building is a widespread practice among athletes and young individuals. Athletes and bodybuilders are using these substances for various purposes, such as enhancing muscle mass, strengthening their bodies, and enhancing their performances. AAS exert a wide range of physiological effects that result in the activation of central signaling, resulting in adverse effects. Moreover, excessive use of AAS which can be categorized as AAS abuse; is linked to biological and psychological pathologies, which can lead to mortality. Complications arising from steroid abuse involve both cellular and physiological complications. Cellular complications arise when activation of signaling proteins like mTOR, Akt, etc. leads to alteration in protein synthesis pathways, cell cycle, oxidative stress, and apoptosis, contributing to damage at the cellular level. Physiological complications are evident with cardiovascular pathologies, including an altered lipid profile, cardiac hypertrophy, hypogonadism after discontinuation of AAS, and modulation of GABA receptors in the brain, all contributed by the androgen receptor signaling. Clinical complications budding from these altered physiological processes lead to clinical effects like testicular dysfunction, acne, gynecomastia, and neuropsychiatric disorders. Despite potential therapeutic benefits, AAS use is prohibited by the World Anti-Doping Agency (WADA) due to concerns over adverse health effects. This review highlights the molecular mechanisms, physiological processes, and clinical complications arising from the excessive use of AAS among athletes.

Comparison of Pollutant Effects on Cutaneous Inflammasomes Activation

The skin is the outermost layer of the body and, therefore, is exposed to a variety of stressors, such as environmental pollutants, known to cause oxinflammatory reactions involved in the exacerbation of several skin conditions. Today, inflammasomes are recognized as important modulators of the cutaneous inflammatory status in response to air pollutants and ultraviolet (UV) light exposure. In this study, human skin explants were exposed to the best-recognized air pollutants, such as microplastics (MP), cigarette smoke (CS), diesel engine exhaust (DEE), ozone (O3), and UV, for 1 or 4 days, to explore how each pollutant can differently modulate markers of cutaneous oxinflammation. Exposure to environmental pollutants caused an altered oxidative stress response, accompanied by increased DNA damage and signs of premature skin aging. The effect of specific pollutants being able to exert different inflammasomes pathways (NLRP1, NLRP3, NLRP6, and NLRC4) was also investigated in terms of scaffold formation and cell pyroptosis. Among all environmental pollutants, O3, MP, and UV represented the main pollutants affecting cutaneous redox homeostasis; of note, the NLRP1 and NLRP6 inflammasomes were the main ones modulated by these outdoor stressors, suggesting their role as possible molecular targets in preventing skin disorders and the inflammaging events associated with environmental pollutant exposure.

A comparative NMR-based metabolomics study of lung parenchyma of severe COVID-19 patients.

COVID-19 was the most significant infectious-agent-related cause of death in the 2020-2021 period. On average, over 60% of those admitted to ICU facilities with this disease died across the globe. In severe cases, COVID-19 leads to respiratory and systemic compromise, including pneumonia-like symptoms, acute respiratory distress syndrome, and multiorgan failure. While the upper respiratory tract and lungs are the principal sites of infection and injury, most studies on the metabolic signatures in COVID-19 patients have been carried out on serum and plasma samples. In this report we attempt to characterize the metabolome of lung parenchyma extracts from fatal COVID-19 cases and compare them with that from other respiratory diseases. Our findings indicate that the metabolomic profiles from fatal COVID-19 and non-COVID-19 cases are markedly different, with the former being the result of increased lactate and amino acid metabolism, altered energy pathways, oxidative stress, and inflammatory response. Overall, these findings provide additional insights into the pathophysiology of COVID-19 that could lead to the development of targeted therapies for the treatment of severe cases of the disease, and further highlight the potential of metabolomic approaches in COVID-19 research.

The Role of Epigenetic Control of Mitochondrial (Dys)Function in MASLD Onset and Progression.

Metabolic dysfunction-associated steatotic fatty liver disease (MASLD), a novel definition for NAFLD, represents one of the most common causes of liver disease, and its incidence is increasing worldwide. It is characterized by a complex etiopathogenesis in which mitochondrial dysfunction exerts a pivotal role together with alteration of lipid metabolism, inflammation, and oxidative stress. Nutrients and bioactive compounds can influence such mechanisms so that changes in diet and lifestyle are regarded as important treatment strategies. Notably, natural compounds can exert their influence through changes of the epigenetic landscape, overall resulting in rewiring of molecular networks involved in cell and tissue homeostasis. Considering such information, the present review aims at providing evidence of epigenetic modifications occurring at mitochondria in response to natural and bioactive compounds in the context of liver (dys)function. For this purpose, recent studies reporting effects of compounds on mitochondria in the context of NAFLD/MASLD, as well as research showing alteration of DNA methylation and non-coding RNAs-related circuits occurring at liver mitochondria, will be illustrated. Overall, the present review will highlight the importance of understanding the bioactive compounds-dependent epigenetic modulation of mitochondria for improving the knowledge of MASLD and identifying biomarkers to be employed for effective preventative strategies or treatment protocols.

Children with Autism Spectrum Disorder Exhibit Elevated Physical Activity and Reduced Sedentary Behavior.

According to previous research, individuals with autism spectrum disorder (ASD) have lower levels of physical activity than their typically developed (TD) counterparts. There have been conflicting reports about physical activity (PA) levels in people with ASD. Given the conflicting evidence, further investigation is required. We believe that evaluating PA in individuals with ASD is critical in order to offer PA intervention plans aiming at increasing their health-related physical fitness on a daily, systematic, and individualized basis. In the current study, an ActiGraph monitor (GT3X+) was used to accurately measure PA and sedentary activity in 21 children with autism aged 6.43 ± 2.29 years and 30 TD children aged 7.2 ± 3.14 years. Our data indicated that while the light and moderate activity counts were not significantly different between the two groups, the vigorous activity was significantly higher in ASD compared to TD. This finding was attributed to ASD characteristic stereotypy and self-stimulating behaviors. The significantly higher vigorous PA is discussed in relation to altered neurochemistry, oxidative stress, and neuroinflammation as etiological mechanisms in ASD. This research provides a better understanding of the status of PA participation in individuals with ASD.

Intestinal fat absorption shifting by polyglucosamine biopolymer: control of lipids and reduction of progression of early subclinical atherosclerosis.

Atherosclerosis progression is possible in subjects with limited alteration of body weight, lipid profile, and oxidative stress. The ultrasound carotid thickness (IMT) and arterial wall modification (granulation and bubbles) are evident signs of the disease. Intestinal fats absorption shifting (IFAS) is expected to prevent or reduce the arterial damage. The aim of the registry was to evaluate the effects of a mild diet in association with lifestyle modifications (standard management [SM]) and SM+ a polyglucosamine biopolymer (BP) shifting the intestinal absorption of dietary fats. The present is a two-year registry comparing two groups of otherwise healthy subjects, respectively 150 (SM) and 144 (SM+BP). BP was administered at the dosage of 3g/day. IMT and relative arterial damages were measured together with lipid profile, oxidative stress, anthropometric and vital measures. The two groups at the baseline were comparable for all variables: 8 cases of drop out were found limited to SM. Compliance with BP was optimal (>97%) and no side effect were observed. IMT showed a significant decrease in thickness (P<0.05) using BP+SM, while increased in SM group. Intimal granulations and lipid wall bubbles were also significantly decreased with BP in comparison to SM only (P<0.05). BMI significantly decreased with BP (P<0.05) as well as BW, fat mass, lipid profile and oxidative stress in comparison to SM only. A positive variation in blood pressure and heart rate (P<0.05) was also observed. BP allows IFAS to improve early subclinical arterial lesions that tend to progress to plaques and clinical events. The long-term and safe treatment of BP is effective on IMT, lipids, BW, and early lesions of the arterial wall structure in subjects with subclinical conditions. BP also reduces oxidative stress which contributes to lipid oxidation and deposition into the arterial wall layer in areas of high dynamic stress (arterial bifurcations).

CysLTR1 antagonism by montelukast can ameliorate diabetes-induced aortic and testicular inflammation

AimsMontelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic and testicular tissues is unknown. This study investigated the effect of CysLTR1 antagonism by montelukast on toll-like receptor (TLR)4 and nuclear factor kappa B (NF-κB) pathways in diabetes-induced aortic and testicular injury. MethodsAdult male Sprague-Dawley rats were made diabetic with Streptozotocin (STZ, 55 mg/kg). Following this, Streptozotocin-induced diabetic (SD) rats were administered montelukast (10 and 20 mg/kg, orally) for 8 weeks. Blood glucose, serum malondialdehyde (MDA), inflammatory markers, and histopathology were evaluated. ResultsMontelukast showed protection against diabetic complications, as evidenced by the ameliorative effect against STZ-induced alterations in oxidative stress as indicated by serum MDA levels. Moreover, montelukast conferred a significant decrease in the aortic and testicular levels of CysLTR1, TLR4, and NF-κB with a subsequent decrease in the levels of NOD-like receptor family pyrin domain containing (NLRP)3, caspase 1, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α. Additionally, administration of montelukast resulted in autophagy stimulation, as shown by decreased p62/Sequestosome (SQSTM)1 levels. Finally, montelukast protection resulted in normal thickness of whole aortic wall, regular tunica (t.) intima, mild vacuolation of smooth muscle fibers in aorta, increased size of seminiferous tubules, and increased spermatogenesis in testis as demonstrated by histopathology. ConclusionsThe protective effect of montelukast against diabetes-induced aortic and testicular injury is due to its antioxidant, anti-inflammatory, and autophagy stimulation characteristics.

Between eustress and distress: UVB induced changes in carotenoid accumulation in halophytic Salicornia europaea

Halophytes are potential future crops with a valuable nutritional profile. Produced in indoor farming, they are considered to contribute to sustainable and resilient food systems. Indoor farms operate using artificial light. In this context narrowband and low dose UVB radiation can be used to increase plant secondary metabolites, such as carotenoids, and provide an improved nutritional profile for a human diet. UVB radiation can cause eustress or distress in the plant depending on the lighting situation. The aim of this study was to identify the doses of UVB that lead to either eustress or distress and to analyze these responses in Salicornia europaea. Therefore, S. europaea plants were exposed to different UVB radiation levels, low, medium and high, and analyzed for reactive oxygen species (ROS), plant hormones, amino acids, and photosynthetic pigments. High UVB treatment was found to affect phenotype and growth, and the metabolite profile was affected in a UVB dose-dependent manner. Specifically, medium UVB radiation resulted in an increase in carotenoids, whereas high UVB resulted in a decrease. We also observed an altered oxidative stress status and increased SA and decreased ABA contents in response to UVB treatment. This was supported by the results of menadione treatment that induces oxidative stress in plants, which also indicated an altered oxidative stress status in combination with altered carotenoid content. Thus, we show that a moderate dose of UVB can increase the carotenoid content of S. europaea. Furthermore, the UVB stress-dependent response led to a better understanding of carotenoid accumulation upon UVB exposure, which can be used to improve lighting systems and in turn the nutritional profile of future crops in indoor farming.

Evaluation of Diacerein Efficacy on Colitis as Anti-inflammatory and Anti-oxidant and its Role in Enhancing of Colon Barrier in Mice

Ulcerative colitis (UC) is a prevalent disorder characterized by oxidative stress and the release of pro-inflammatory cytokines that disturb the colonic mucosa. Currently, available medicines for UC remain unsatisfactory. Diacerein (DIAC) has exhibited anti-oxidant and anti-inflammatory properties in wide inflammatory disorders. However, the limited understanding of DIAC's role in bowel inflammation has necessitated the investigation of its efficacy in dextran sodium sulfate (DSS)-induced UC in Balb/c mice in this study. Fifty mice were equally divided into five groups. Except for the control, all groups were given DSS for seven days to induce the colitis model. The model was treated with 25 and 50mg/kg/day of DIAC and 00mg/kg/day of 5-aminosalicylic acid (5-ASA) for ten days. Several clinical, molecular and biochemical parameters were evaluated. Following the exposure to DSS, there was a significant upregulation in the pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) and oxidative stress index (MDA). Meanwhile, the concentration of anti-oxidative stress indices (SOD, GPx and CAT) and the levels of IL-10, mucin-1 and 2 and tight junction proteins (TJs) ZO-1 and occludin were markedly suppressed. The colon length and body weight were reduced while DAI and myeloperoxidase (MPO) were elevated. Conversely, DIAC 50mg and 5-ASA significantly reversed the altered pro-inflammatory cytokines, oxidative stress and MPO. Moreover, they significantly restored body weight, colon length, DAI, TJs, mucin-1 and 2 and IL-10. No significant results were found with DIAC 25mg. In conclusion, DIAC exhibited therapeutic effectiveness against colitis. This research may provide hope for testing its effectiveness against UC in humans

Lactobacillus intestinalis/Lactobacillus rhamnosus protects against AFB1-induced liver damage: involvement of intestinal mucosal barrier

Aflatoxin B1 (AFB1) is a widely spread mycotoxin that poses a threat to the healthy to human and animals. The liver is the main target organ for AFB1-induced damage, primarily causing inflammatory injury and oxidative stress. When AFB1 enters the body, it can damage the intestinal barrier function, and its metabolites are transported to the liver. Therefore, the damage to the liver is closely associated with intestinal barrier impairment. Lactobacillus plays a crucial role in mitigating liver damage by improving the intestinal barrier function. In our previous report, we reported that Lactobacillus reduces liver damage caused by AFB1. However, it is still unclear how the intestinal barrier contributes to the protective effects of Lactobacillus against AFB1. To investigate the protective effects and intestinal barrier mechanisms of Lactobacillus intestinals /rhamnosus against AFB1-induced liver damage, we orally administered AFB1 and Lactobacillus intestinals/rhamnosus to male SD rats. Then the body weight, organ index, histopathological changes in the liver and gut, liver and kidney function indicators, intestinal mucosal barrier indicators, serum AFB1 content and inflammatory factors, liver oxidative stress index, and short-chain fatty acids content were analyzed. Our findings demonstrate that exposure to AFB1 resulted in changes in liver histopathology and biochemical functions, altered inflammatory response and oxidative stress, compromised the intestinal mucosal barrier, and induced the accumulation of inflammatory factor and inflammation in the liver. However, supplementation with Lactobacillus intestinals or Lactobacillus rhamnosus significantly prevented AFB1-induced liver injury, alleviated histopathological changes and hepatic injury by the maintenance of intestinal mucosal barrier integrity.

Identification of Fibrotic Biomarkers Associated with Macrophages in Diabetic Nephropathy.

BACKGROUND Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Renal fibrosis is an important pathological feature of kidney injury, and the therapeutic means are very limited. The functions of macrophages play important roles in renal fibrosis. There is a complicated link between altered immune metabolism and oxidative stress. Hence, we designed this study to identify the oxidative stress- and macrophage-relevant biomarkers reflecting fibrosis in DN. MATERIAL AND METHODS Differential expression analysis was performed based on the GSE96804 dataset. xCell and weighted gene co-expression network analysis were used to determine the distinctions in infiltrating immune cells between DN and control specimens. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted. A protein-protein interaction network was constructed to identify the hub genes. Hub genes were validated in an external dataset, GSE30528, and cell models. RESULTS MMP2, CASP3, and HIF-1alpha were identified as biomarkers, which were upregulated in the DN group and positively correlated with the infiltration of macrophages and M1 macrophages. In vitro, the 3 genes were highly expressed in murine MPC5 cells treated with high glucose and human THP-1 macrophages treated with advanced glycation end products. CONCLUSIONS Our results provided biomarkers for predicting the fibrotic progression of DN and confirmed that MMP2, CAPS3, and HIF-1alpha have good diagnostic value. They might be involved in the progression of DN fibrosis by regulating oxidative stress and macrophage recruitment or polarization.

Stalling the Course of Neurodegenerative Diseases: Could Cyanobacteria Constitute a New Approach toward Therapy?

Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.

N-Acetylcysteine may exert hepatoprotective effect by regulating Meteorin-Like levels in Adriamycin-induced liver injury.

Adriamycin (ADR) is an important chemotherapeutic drug, but it has serious side effects such as hepatotoxicity. This study aimed to evaluate whether N-acetylcysteine (NAC) has hepatoprotective effects against ADR-induced hepatotoxicity in rats. In addition, it was aimed to determine how Meteorin-Like (MtrnL), which has pleiotropic effects on immunology, inflammation, and metabolism, is affected by ADR and/or NAC applications in liver tissue. 28 rats were randomly assigned to one of four equal groups in the study: control (no treatment), NAC (150mg/kg/day of NAC intraperitoneally (i.p), ADR (15mg/kg only on the first day of the experiment), and ADR + NAC (ADR 15mg/kg on the first day of the experiment + 150mg/kg/day NAC i.p). After 15days, liver enzyme levels in serum, oxidant/antioxidant parameters in liver tissue, histopathological changes, caspase 3 (Casp3) and heat shock protein 70 (HSP-70) immunoreactivities, and MtrnL levels were examined. Histopathological changes, liver enzyme levels, as well as HSP-70, and Casp3 immunoreactivities increased due to ADR application. Additionally, MtrnL levels in liver tissue were significantly increased as a result of ADR application. However, it was detected that the NAC application significantly regulated the ADR-induced changes. Furthermore, it was determined that NAC administration regulated the changes in ADR-induced oxidative stress parameters. We propose that NAC may exert a hepatoprotective effect by regulating ADR-induced altered oxidative stress parameters, MtrnL levels, Casp3, and HSP-70 immunoreactivities in the liver.