Oxidative Stress Protection Research Articles

Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development.

Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions.

TOMM40-APOE chimera linking Alzheimer's highest risk genes: a new pathway for mitochondria regulation and APOE4 pathogenesis.

The patho-mechanism of apolipoprotein variant, APOE4, the strongest genetic risk for late-onset Alzheimer's disease (AD) and longevity, remains unclear. APOE's neighboring gene, TOMM40 (mitochondria protein transport channel), is associated with brain trauma outcome and aging-related cognitive decline, however its role in AD APOE4-independently is controversial. We report that TOMM40 is prone to transcription readthrough into APOE that can generate spliced TOMM40-APOE mRNA chimera (termed T9A2) detected in human neurons and other cells and tissues. T9A2 translation tethers APOE (normal APOE3 or APOE4) to near-full-length TOM40 that is targeted to mitochondria. Importantly, T9A2-APOE3 boosts mitochondrial bioenergetic capacity and decreases oxidative stress significantly more than T9A2-APOE4 and APOE3, and lacking in APOE4. We describe detailed interactomes of these actors that may inform about the activities and roles in pathogenesis. T9A2 uncovers a new candidate pathway for mitochondria regulation and oxidative stress-protection that are impaired in APOE4 genotypes and could initiate neurodegeneration.

Elucidation of Spartina dimethylsulfoniopropionate synthesis genes enables engineering of stress tolerant plants

The organosulfur compound dimethylsulfoniopropionate (DMSP) has key roles in stress protection, global carbon and sulfur cycling, chemotaxis, and is a major source of climate-active gases. Saltmarshes are global hotspots for DMSP cycling due to Spartina cordgrasses that produce exceptionally high concentrations of DMSP. Here, in Spartina anglica, we identify the plant genes that underpin high-level DMSP synthesis: methionine S-methyltransferase (MMT), S-methylmethionine decarboxylase (SDC) and DMSP-amine oxidase (DOX). Homologs of these enzymes are common in plants, but differences in expression and catalytic efficiency explain why S. anglica accumulates such high DMSP concentrations and other plants only accumulate low concentrations. Furthermore, DMSP accumulation in S. anglica is consistent with DMSP having a role in oxidative and osmotic stress protection. Importantly, administration of DMSP by root uptake or over-expression of Spartina DMSP synthesis genes confers plant tolerance to salinity and drought offering a route for future bioengineering for sustainable crop production.

Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells.

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.

Activated THP-1 Macrophage-Derived Factors Increase the Cytokine, Fractalkine, and EGF Secretions, the Invasion-Related MMP Production, and Antioxidant Activity of HEC-1A Endometrium Cells.

Endometrium receptivity is a multifactor-regulated process involving progesterone receptor-regulated signaling, cytokines and chemokines, and additional growth regulatory factors. In the female reproductive system, macrophages have distinct roles in the regulation of receptivity, embryo implantation, immune tolerance, and angiogenesis or oxidative stress. In the present study, we investigated the effects of PMA-activated THP-1 macrophages on the receptivity-related genes, cytokines and chemokines, growth regulators, and oxidative stress-related molecules of HEC-1A endometrium cells. We established a non-contact co-culture in which the culture medium of the PMA-activated macrophages exhibiting the pro-inflammatory phenotype was used for the treatment of the endometrial cells. In the endometrium cells, the expression of the growth-related factors activin and bone morphogenetic protein 2, the growth hormone EGF, and the activation of the downstream signaling molecules pERK1/2 and pAkt were analyzed by ELISA and Western blot. The secretions of cytokines and chemokines, which are involved in the establishment of endometrial receptivity, and the expression of matrix metalloproteinases implicated in invasion were also determined. Based on the results, the PMA-activated THP-1 macrophages exhibiting a pro-inflammatory phenotype may play a role in the regulation of HEC-1A endometrium cells. They alter the secretion of cytokines and chemokines, as well as the protein level of MMPs of HEC-1A cells. Moreover, activated THP-1 macrophages may elevate oxidative stress protection of HEC-1A endometrium cells. All these suggest that pro-inflammatory macrophages have a special role in the regulation of receptivity-related and implantation-related factors of HEC-1A cells.

Response to chronic crowding stress in shy and bold behavioral groups of male and female zebrafish.

In recent years, there has been a burgeoning interest in exploring the nuances of animal stress physiology, particularly in relation to parameters such as sex and behavioral phenotype-dependent variations, which is crucial for understanding phenotypic variation and its role in evolutionary selection. However, a significant dearth remains in how chronic stressors affect organismal stress physiology concerning the aforesaid parameters. This void is even wider pertaining to the response of peripheral tissues, such as the skin, the organ with the highest surface contact area with the environment. Hence, we behaviorally grouped the zebrafishes based on their boldness and the body condition, whole body cortisol response, along with examining the transcriptional response, global DNA methylome, and oxidative DNA damage in the skin upon chronic crowding. Upon baseline conditions, clear distinction between bold and shy phenotypes was found, particularly in males. The boldness index score distribution exhibited greater uniformity in males than in females. Regarding the body condition response to chronic crowding, shy males showed a significant relative decline compared with their bold counterparts, while this trend did not hold true for females. qPCR data revealed distinctive expression patterns in key genes that play critical roles in cellular processes such as stress-mediated gene regulation, immune response, oxidative stress protection, and maintenance of genomic integrity through epigenetic modifications across behavioral phenotypes and sexes under both with and without chronic crowding stress. Global DNA methylation levels significantly declined only in chronically crowded shy males, and sex/behavioral phenotype-dependent trends in oxidative DNA damage were identified.NEW & NOTEWORTHY This paper analyzes the response of zebrafish to crowding stress through a new approach focused on the peripheral response dynamics of the skin, the main mucosal tissue, and involving sex and behavioral phenotype influences. Shy males showed significant distress as observed by body condition, physiological and transcriptional response, and global DNA methylation. Nuances in stress response across behavioral phenotypes and sex indicate a genetic and behavioral specificity and further inherent epigenetic regulatory dimension.

The Role of Selected Elements in Oxidative Stress Protection: Key to Healthy Fertility and Reproduction.

Oxidative stress and its relationship to fertility and reproduction is a topic of interest in medicine, especially in the context of the effects of trace elements and micronutrients. Oxidative stress occurs when there is an excess of free radicals in the body, which can lead to cell and tissue damage. Free radicals are reactive oxygen species (ROS) that can be formed as a result of normal metabolic processes, as well as under the influence of external factors such as environmental pollution, UV radiation, and diet. Oxidative stress has a significant impact on fertility. In men, it can lead to DNA damage in sperm, which can result in reduced semen quality, reduced sperm motility and increased numbers of defective sperm, and free radical damage to sperm cell membranes causing a reduction in the number of available sperm. In women, oxidative stress can affect the quality of female reproductive cells, which can lead to problems with their maturation and with embryo implantation in the uterus and can also affect ovarian function and disrupt hormonal regulation of the menstrual cycle. A proper balance of trace elements and micronutrients is key to protecting against oxidative stress and maintaining reproductive health. Supplementation with appropriate elements such as zinc, selenium, copper, manganese, chromium, and iron can help reduce oxidative stress and improve fertility. This work discusses the effects of selected elements on oxidative stress parameters specifically in terms of fertility and reproduction.

Changes in AmotL2 Expression in Cells of the Human Enteral Nervous System in Oxaliplatin-Induced Enteric Neuropathy.

Gastrointestinal (GI) toxicity is a common side effect in patients undergoing oxaliplatin (OxPt)-based chemotherapy for colorectal cancer (CRC). Frequently, this complication persists in the long term and could affect the efficacy of the treatment and the patient's life quality. This long-term GI toxicity is thought to be related to OxPt-induced enteral neuropathy. AmotL2 is a member of the Angiomotin family of proteins, which play a role in cell survival, neurite outgrowth, synaptic maturation, oxidative stress protection, and inflammation. In order to assess the role of AmotL2 in OxPt-induced enteral neuropathy, we studied the expression of AmotL2 in cells of the enteric nervous system (ENS) of untreated and OxPt-treated CRC patients and its relationship with inflammation, using immunofluorescence confocal microscopy. Our results in human samples show that the total number of neurons and glial cells decreased in OxPt-treated patients, and TNF-α and AmotL2 expression was increased and colocalized in both neurons and glia. AmotL2 differential expression between OxPt-treated and untreated CRC patients shows the involvement of this scaffold protein in the inflammatory component and toxicity by OxPt in the ENS.

MiR-221 on protective oxidative induced by selenium modified Codonopsis pilosula polysaccharide

Oxidative stress plays an important role in various diseases. miR-221 has been reported to regulate oxidative stress. However, the mechanism of miR-221 in regulating oxidative stress induced by sCPPS5 remains unclear. This study aimed to investigate the protective effects and mechanisms of miR-221 on oxidative stress induced by sCPPS5. The expression of SOD, CAT, MDA, LDH, MMP, caspase-3 activity and apoptosis were measured. In addition, the key signaling factors in the Keap1-Nrf2-ARE signaling pathway were determined by real-time PCR and Western blot. Mice were employed to evaluate the effects of sCPPS5 and the possible mechanism in vivo. sCPPS5 promoted the expression of SOD and CAT and activated Keap1-Nrf2-ARE signaling pathway inhibit the MDA content, MMP, caspase-3 activity, apoptosis and LDH release rate after transfection with miR-221 mimics and inhibitors. Consistently, sCPPS5 has the potential to enhance the expression of antioxidant enzymes as well as upregulate mRNA expression of crucial signal proteins in vivo. miR-221 on oxidative stress protection induced by sCPPS5 possibly through regulating the Keap1-Nrf2-ARE signaling pathway in macrophages.

Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.

Constitutive androstane receptor (CAR, Nr1i3), a liver nuclear receptor and xenobiotic sensor, induces drug, steroid, and lipid metabolizing enzymes, stimulates liver hypertrophy and hyperplasia, and ultimately, hepatocellular carcinogenesis. The mechanisms linking early CAR responses to later disease development are poorly understood. Here we show that exposure of CD-1 mice to TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene), a halogenated xenochemical and selective CAR agonist ligand, induces pericentral steatosis marked by hepatic accumulation of cholesterol and neutral lipid, and elevated circulating alanine aminotransferase, indicating hepatocyte damage. TCPOBOP-induced steatosis was weaker in the pericentral region but stronger in the periportal region in females compared with males. Early (1day) TCPOBOP transcriptional responses were enriched for CAR-bound primary response genes, and for lipogenesis and xenobiotic metabolism and oxidative stress protection pathways; late (2weeks) TCPOBOP responses included many CAR binding-independent secondary response genes, with enrichment for macrophage activation, immune response, and cytokine and reactive oxygen species production. Late upstream regulators specific to TCPOBOP-exposed male liver were linked to proinflammatory responses and hepatocellular carcinoma progression. TCPOBOP administered weekly to male mice using a high corn oil vehicle induced carbohydrate-responsive transcription factor (MLXIPL)-regulated target genes, dysregulated mitochondrial respiratory and translation regulatory pathways, and induced more advanced liver pathology. Overall, TCPOBOP exposure recapitulates histological and gene expression changes characteristic of emerging steatotic liver disease, including secondary gene responses in liver nonparenchymal cells indicative of transition to a more advanced disease state. Upstream regulators of both the early and late TCPOBOP response genes include novel biomarkers for foreign chemical-induced metabolic dysfunction-associated steatotic liver disease.

Impaired HBsAg release and antiproliferative/antioxidant cell regulation by HBeAg-negative patient isolates reflects an evolutionary process.

The hepatitis B e antigen (HBeAg)-negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood. Genotype A, B and D HBeAg-negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg-positive rescue mutant and HBeAg-positive wild-type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent gene expression and cellular kinome. In comparison with reference genomes, the patient isolates are characterized by a lower intra- and extracellular hepatitis B surface antigen (HBsAg)-amount, and HBsAg-retention in the endoplasmic reticulum. Rescue of HBeAg expression increased HBsAg-amount but not its release. Expression of the isolated genomes is associated with a higher Nrf2/ARE-dependent gene expression as compared to reference genomes independent of HBeAg expression. Kinome analyses revealed a decreased activity of receptors involved in regulation of proliferative pathways for all patient isolates compared to the reference genomes. No specific conserved mutations could be found between all genomes from Phase 3. HBeAg-negative genomes from Phase 3 exhibit distinct molecular characteristics leading to lower HBsAg synthesis and release, enhanced oxidative stress protection and decreased activity of key kinases, triggering an antiproliferative stage, which might contribute to the lower probability of hepatocellular carcinoma. The observed differences cannot be associated with loss of HBeAg or specific mutations common to all analysed isolates, indicating the phenotype of Phase 3 derived genomes to be the result of a multifactorial process likely reflecting a conserved natural selection process.

P-368 In vitro culture with rutin and VEGF-A before xenotransplantation protects ovarian tissue from ischemia and oxidative damage but not from growing follicle depletion

Abstract Study question Can pre-treatment with antioxidant and vascular endothelial factor (VEGF-A) help to maintain healthy tissue structure and follicle pool in xenotransplanted human ovarian tissue? Summary answer Rutin and VEGF-A help to prevent fibrosis and oxidative stress damage in grafted ovarian tissue but cannot preserve growing follicles. What is known already Nowadays, ovarian tissue (OT) cryopreservation and autotransplantation become established fertility preservation methods in numerous countries. However, even if hundreds of children has been born thanks to this procedure, most crucial process during which 70-80% of the follicles are lost in the graft is the transplantation itself. As the graft restores vascularisation and regains its function the tissue undergoes ischemia and oxidative stress. There have been attempts made to improve this critical postoperative period by administration of different growth factors, hormones, antoxidants or mechanical tissue damage. Study design, size, duration Pieces of frozen-tharwed OT (2,5 × 2,5 mm) from 10 women were transplanted into immunodeficient mice for 4 weeks. Before xenotransplantation OT fragments were in vitro cultured for 36h in culture media supplemented with 1 μg/ml rutin and 50 ng/ml VEGF-A (n = 10 OT, pretreated grafted) or without (n = 10 OT, non-pretreated grafted). Frozen-thawed OTs were used as non-grafted controls for ischemia-reperfusion injury, apoptosis and follicle loss evaluation. Participants/materials, setting, methods OTs were received from cancer patients (n = 10) undergoing cryopreservation at National Cancer Institute. Xenotransplantation was performed at Life Sciences Centre, Vilnius University. Retrieved grafts were devided into one small piece for immunochistochemical evaluation of α-SMA and apoptosis by TUNEL, and one bigger piece for qPCR analysis of genes related to tissue integrity (PRDX1, SOD1, FN1, COL6A1, CASP3, ANGPT2, mouse CD31) and follicle development (FOXO3, FSHR, GDF9), house keeping gene being GAPDH/Gapdh. Main results and the role of chance After 4 weeks of grafting, multiple genes and protein expressions were evaluated. Vascularisation evaluation: compared to non-grafted group, in grafted OTs we observed significantly more vessels (α-SMA staining, p < 0.0001 and ANGPT2 expression, p < 0.05), as well 1,5-fold higher relative expression of mouse CD31 in pretreated grafted group vs non-pretreated grafted group. Qxidative stress and apoptosis evaluation: expression of SOD2, PRDX1 and CASP3 genes was lower in both grafted groups compared to non-grafted control, significant alterations between xenotransplanted groups were found. Structural gene evaluation: in non-grafted control we could find higher expression of COL6A1 and FN1 genes compared to grafted groups and statistical difference of COL6A1 expression in between grafted groups (p < 0.05). Follicle pool evaluation: primordial follicle activation was measured by FOXO3 gene expression change, though we did not find significant differences between any of three groups, p = 0.06 was observed between grafted OT groups. Maturing follicles were evaluated by expression changes in GDF9 and FSHR genes. We observed significant decrese in expression of these genes in grafted groups (p < 0.05). Results from TUNEL are awaited, thus are the quantification of apoptotic cells, which will provide valuable insights for correlation with vascularisation and oxidative stress. Limitations, reasons for caution This study was performed only in a long-term xenotransplantation setting, we cannot know if rutin and VEGF-A had a significant influence during the first days of OT transplantation. Due to the small size of OT grafted, counting and distribution of follicles was not performed, Wider implications of the findings This study shows that pretreatment of OTs with rutin and VEGF-A could be potentially used in human setting due to protection of ischemia and oxidative stress, especially if the survival of growing follicles is not required, as it is in cases of prepubertal girls. Trial registration number not applicable

UV light and adaptive divergence of leaf physiology, anatomy, and ultrastructure drive heat stress tolerance in genetically distant grapevines.

The genetic basis of plant response to light and heat stresses had been unveiled, and different molecular mechanisms of leaf cell homeostasis to keep high physiological performances were recognized in grapevine varieties. However, the ability to develop heat stress tolerance strategies must be further elucidated since the morpho-anatomical and physiological traits involved may vary with genotype × environment combination, stress intensity, and duration. A 3-year experiment was conducted on potted plants of Sardinian red grapevine cultivars Cannonau (syn. Grenache) and Carignano (syn. Carignan), exposed to prolonged heat stress inside a UV-blocking greenhouse, either submitted to low daily UV-B doses of 4.63 kJ m-2 d-1 (+UV) or to 0 kJ m-2 d-1 (-UV), and compared to a control (C) exposed to solar radiation (4.05 kJ m-2 d-1 average UV-B dose). Irrigation was supplied to avoid water stress, and canopy light and thermal microclimate were monitored continuously. Heat stress exceeded one-third of the duration inside the greenhouse and 6% in C. In vivo spectroscopy, including leaf reflectance and fluorescence, allowed for characterizing different patterns of leaf traits and metabolites involved in oxidative stress protection. Cannonau showed lower stomatal conductance under C (200 mmol m-2 s-1) but more than twice the values inside the greenhouse (400 to 900 mmol m-2 s-1), where water use efficiency was reduced similarly in both varieties. Under severe heat stress and -UV, Cannonau showed a sharper decrease in primary photochemical activity and higher leaf pigment reflectance indexes and leaf mass area. UV-B increased the leaf pigments, especially in Carignano, and different leaf cell regulatory traits to prevent oxidative damage were observed in leaf cross-sections. Heat stress induced chloroplast swelling, plastoglobule diffusion, and the accumulation of secretion deposits in both varieties, aggravated in Cannonau -UV by cell vacuolation, membrane dilation, and diffused leaf blade spot swelling. Conversely, in Carignano UV-B, cell wall barriers and calcium oxalate crystals proliferated in mesophyll cells. These responses suggest an adaptive divergence among cultivars to prolonged heat stress and UV-B light. Further research on grapevine biodiversity, heat, and UV-B light interactions may give new insights on the extent of stress tolerance to improve viticulture adaptive strategies in climate change hotspots.

Reduction of oxidative stress response and protection of liver and renal cell functions by reduced glutathione in lower limb arterial ischemia–reperfusion in New Zealand white rabbits with high triglyceride levels

ObjectiveAcute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia–reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated. MethodsNew Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated. ResultsAfter IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted. ConclusionThis study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

Antioxidant Activities and Protective Effects of Shorea macrophylla Leaf and Bark Extracts

Shorea macrophylla, also known as the ‘Engkabang’ tree or Light Red Meranti, is renowned for its role in reforestation efforts. Despite lacking records of traditional use, the reported biological activities of other species within the Shorea genus spark curiosity about the potential biological activities of this plant. Therefore, this study aims to explore the antioxidant capabilities of S. macrophylla leaf and bark extracts, along with their protective effects against oxidative stress using a brine shrimp model. In the evaluation of antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays were employed. Extracts were incubated in DPPH and FRAP solutions, and absorbances were measured at 517 and 593 nm, respectively. The brine shrimp lethality assay (BSLT) involved exposing brine shrimps (Artemia salina) to various concentrations of the extract, with LC50 values determined through probit regression analysis. Oxidative stress protection assays entailed treating brine shrimps with safe doses of S. macrophylla extracts before exposure to H2O2, with subsequent observation of survival rates. The DPPH assay unveiled IC50 values of 1.025 and 0.693 mg/mL for S. macrophylla leaf and bark extracts, respectively, while FRAP values exhibited a concentration-dependent relationship. BSLT demonstrated concentration-dependent mortality, with LC50 values of 0.93 and 0.6455 mg/mL for S. macrophylla leaf and bark extracts, respectively. Pre-treatment with S. macrophylla extracts significantly increased brine shrimp survival against H2O2-induced oxidative stress. In conclusion, both S. macrophylla leaf and bark water extracts demonstrated noteworthy antioxidant activities and exhibited protective effects against oxidative stress in brine shrimps. These findings provide insights into the antioxidant activities and protective effects of S. macrophylla Leaf and Bark extracts.

The Incorporation of Clove Essential Oil into Nanostructured Lipid Carrier for Improvement of the Delivery and Antioxidant Effects on the Fibroblast Cells.

Clove (Syzygium aromaticum) essential oil (CO) has been studied extensively for its antioxidant properties but faces several limitations, including high volatility, low aqueous solubility, and irritation. We aimed to develop a Nanostructured Lipid Carrier (NLC) to enhance the benefits of CO. Using the emulsification sonication method, a liquid lipid component, surfactant concentration, and a co-surfactant were optimized to create CO-loaded NLC (CO-NLC). The developed CO-NLC was rigorously assessed for its stability during storage. Free radical scavenging activity and fibroblast oxidative stress protection were also measured to assess the antioxidant activity. The CO-NLC displayed a spherical shape with a hydrodynamic diameter of 125.77 ± 29.68 nm, homogenous particle distribution with polydispersity index of 0.26 ± 0.09, and a surface charge of -27.30 ± 4.56 mV with an encapsulation efficiency of 97% and a good stability profile. Furthermore, free CO and CO-NLC displayed very strong free radical scavenging activity with the IC50 value of 22.74 ± 0.57 µg/mL and 18.28 ± 2.63 µg/mL, respectively. However, only CO-NLC managed to protect fibroblast cells from the harmful effects of oxidative stress. The NLC formulations improved free radical scavenging activity and effectively protected fibroblasts from oxidative stress compared to free CO.

The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus.

Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron-carbon limitation alters oxidative stress responses, Aspergillus fumigatus was cultured in glucose-peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes, only the cat2 catalase-peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless of culturing conditions in oxidative stress protection, while the enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g., iron availability or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy.

Laboratory Puzzle of Oxidative Stress, Parameters of Hemostasis and Inflammation in Hospitalized Patients with COVID-19.

Bearing in mind that coronavirus disease (COVID-19) is associated with a wide range of laboratory abnormalities, the aim of this study was to examine the importance of determining the parameters of oxidative stress and antioxidant protection as well as markers of inflammation and hemostasis in hospitalized patients with COVID-19. The study population included 105 patients with severe COVID-19 and 65 healthy control subjects. The parameters of oxidative stress and the activity of enzymes of the antioxidant system were determined from the obtained samples using spectrophotometric methods. Standard laboratory methods were performed for the determination of the biochemical and hematological parameters. Patients with COVID-19 showed a significantly higher level of pro-oxidative parameters (hydrogen peroxide (H2O2) and the index of lipid peroxidation in the form of thiobarbituric acid-reactive substances (TBARSs)) and a significantly lower activity of the antioxidant system (catalase (CAT)). Patients with COVID-19 had significantly higher values of inflammation parameters (C-reactive protein (CRP), procalcitonin (PCT), ratio of the number of neutrophils to lymphocytes (NLR), and ratio of the number of platelets to lymphocytes (PLR)) and parameters of hemostasis (activated partial thromboplastin time (aPTT), prothrombin time (PT), D-dimer, fibrinogen) than the control healthy subjects. In addition, changes in hemostatic parameters correlated positively with inflammatory markers in the group of patients with COVID-19. The early determination of hemostasis parameters and the parameters of inflammation can help in the prediction of poor prognosis in COVID-19 patients.

Chronic Kidney Disease and Oxidative Stress

Disturbance of the balance between production of oxygen free radicals (or some other radical species) and activity of antioxidative system of protection causes the so called oxidative stress Protection of an organism from oxygen free radicals implies activity of enzymatic (catalase, SOD, glutathione peroxidase, glutathione reductase etc.) and nonenzymatic (vitamin E. vitamin C. glutathione, uric acid etc.) systems of protection.

Ecophysiological and genomic approaches to cyanobacterial hardening for restoration.

Cyanobacteria inhabit extreme environments, including drylands, providing multiple benefits to the ecosystem. Soil degradation in warm drylands is increasing due to land use intensification. Restoration methods adapted to the extreme stress in drylands are being developed, such as cyanobacteria inoculation to recover biocrusts. For this type of restoration method to be a success, it is crucial to optimize the survival of inoculated cyanobacteria in the field. One strategy is to harden them to be acclimated to stressful conditions after laboratory culturing. Here, we analyzed the genome and ecophysiological response to osmotic desiccation and UVR stresses of an Antarctic cyanobacterium, Stenomitos frigidus ULC029, which is closely related to other cyanobacteria from warm and cold dryland soils. Chlorophyll a concentrations showed that preculturing ULC029 under moderate osmotic stress improved its survival during an assay of desiccation plus rehydration under UVR. Additionally, its sequential exposure to these stress factors increased the production of exopolysaccharides, carotenoids, and scytonemin. Desiccation, but not osmotic stress, increased the concentrations of the osmoprotectants trehalose and sucrose. However, osmotic stress might induce the production of other osmoprotectants, for which the complete pathways were observed in the ULC029 genome. In total, 140 genes known to be involved in stress resistance were annotated. Here, we confirm that the sequential application of moderate osmotic stress and dehydration could improve cyanobacterial hardening for soil restoration by inducing several resistance mechanisms. We provide a high-quality genome of ULC029 and a description of the main resistance mechanisms (i.e., production of exopolysaccharides, osmoprotectants, chlorophyll, and carotenoids; DNA repair; and oxidative stress protection).