Oxidative Homeostasis Research Articles

New synthetic derivatives of isoindoline-dione: synthesis, neuroprotection assay and impact on the expression level of oxidative stress-related genes in neuronal-like cell line

Purpose Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer’s, Parkinson’s, and Huntington’s. This study looked at newly synthesized isoindole derivatives and their effects on SH-SY5Y as a neuroblastoma cell under oxidative stress through the NRF2 signaling pathway. NRF2 transcription factor plays a vital role in the oxidative stress response and cellular homeostasis. Method Three isoindoline-dione derivatives were synthesized by reacting phthalic anhydrides with 4-(2-aminoethyl)-1-benzyl piperidine. Their structures were confirmed through FT-IR, NMR, and Mass spectroscopy. The derivatives were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). The cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes were measured after 24 h. Results Three isoindoline derivatives (3a–3c) were observed to increase the viability of SH-SY5Y cells by protective against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as NQO-1, and GSTK1. Conclusion Isoindoline derivatives demonstrated a neuroprotective effect on SH-SY5Y cells through various neuroprotective mechanisms, although more studies are needed.

Neuroprotection by agmatine: Possible involvement of the gut microbiome?

Agmatine, an endogenous polyamine derived from L-arginine, elicits tremendous multimodal neuromodulant properties. Alterations in agmatinergic signalling are closely linked to the pathogeneses of several brain disorders. Importantly, exogenous agmatine has been shown to act as a potent neuroprotectant in varied pathologies, including brain ageing and associated comorbidities. The antioxidant, anxiolytic, analgesic, antidepressant and memory-enhancing activities of agmatine may derive from its ability to regulate several cellular pathways; including cell metabolism, survival and differentiation, nitric oxide signalling, protein translation, oxidative homeostasis and neurotransmitter signalling. This review briefly discusses mammalian metabolism of agmatine and then proceeds to summarize our current understanding of neuromodulation and neuroprotection mediated by agmatine. Further, the emerging exciting bidirectional links between agmatine and the resident gut microbiome and their implications for brain pathophysiology and ageing are also discussed.

Sigma1 Regulates Lipid Droplet-mediated Redox Homeostasis Required for Prostate Cancer Proliferation.

To proliferate, cancer cells must maintain productive metabolic and oxidative stress (eustress) while mitigating destructive, uncontrolled oxidative stress (distress). LDs are metabolic hubs that enable adaptive responses to promote eustress. Targeting the unique Sigma1 protein can trigger distress by disrupting the LD-mediated homeostasis required for proliferation.

CORRECTION OF THE METABOLOMIC PROFILE AND REDOX POTENTIAL IN PATIENTS WITH LOWER LIMB VARICOSE VEINS (CLASS C4 - C6) IN THE POSTOPERATIVE PERIOD

The present study evaluates the effectiveness of the use of sulodexin (SDX) and ozone therapy in the treatment of lower limb varicose veins (classes C4 to C6) based on the study of the dynamics of plasma biomarkers of oxidative homeostasis and metabolomic profile. In patients of the comparison group, changes in the TAC index in blood plasma tended to increase, however, we didn’t established any statistical significance for the entire period of the study: initially - 305.5 ± 18.6 nmol/ml, then 322.3±17.7 nmol/ml on the day 20 after SI (surgical intervention), and 341.6±18.2 nmol/ml (p=0.672) on day 45 after SI. On the contrary, patients of the main group, by the day 20 after SI, had an increase in TAC level from 305.5±18.6 nmol/ml to 365.9±18.1 nmol/ml (by 19.8% of the baseline, p=0.046 ). By the day 20 after SI, in patients of the comparison group, the SOD activity in blood plasma tended to increase from 10.8±1.8 U/ml to 13.1±1.5 U/ml (by 21.3% relative to the baseline), but no statistical significance was found (p=0.733). The proposed method of complex treatment proved to be effective in correcting oxidative homeostasis and cellular metabolomic profile in patients with LLVV (classes C4 to C6).

A novel zinc finger transcription factor, BcMsn2, is involved in growth, development, and virulence in Botrytis cinerea.

Reactive oxygen species (ROS) are important for plant defense against fungal attack. As a necrotrophic fungus, Botrytis cinerea can exploit ROS that originated from both sides of the host and pathogen during interaction to facilitate its infestation. Meanwhile, B. cinerea needs to exert an efficient oxidative stress responsive system to balance the intracellular redox state when encountering deleterious ROS levels. However, the machinery applied by B. cinerea to cope with ROS remains obscure. Herein, we investigated the role of the transcription factor BcMsn2 in regulating B. cinerea redox homeostasis. Disruption of the BcMsn2 gene severely impaired vegetative growth, sclerotium formation, conidial yield, and fungal virulence. The intracellular oxidative homeostasis of the ∆bcmsn2 mutant was disrupted, leading to significantly elevated levels of ROS and reduced activities of enzymes closely associated with oxygen stress, such as catalase (CAT) and superoxide dismutase (SOD). RNA-Seq and qRT-PCR analyses showed remarkable downregulation of the expression of several genes encoding ROS scavenging factors involved in maintaining the redox homeostasis in ∆bcmsn2, suggesting that BcMsn2 functions as a transcriptional regulator of these genes. Our findings indicated that BcMsn2 plays an indispensable role in maintaining the equilibrium of the redox state in B. cinerea, and intracellular ROS serve as signaling molecules that regulate the growth, asexual reproduction, and virulence of this pathogen.

Saponins of Tomato Extract Improve Non-Alcoholic Fatty Liver Disease by Regulating Oxidative Stress and Lipid Homeostasis.

The present study investigated the impact of saponins of tomato extract (STE) on non-alcoholic fatty liver disease (NAFLD). The findings demonstrated that introducing STE in NAFLD mice revealed promising results in ameliorating symptoms of oxidative stress, lipid metabolism disorders, visceral fat deposition and fatty liver disease. Moreover, the mechanistic studies have demonstrated that STE delivers its effects by activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), thereby suppressing downstream protein expression associated with fatty acid synthesis. In such conditions, lipid metabolism can be improved. Simultaneously, STE enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) and entry into the nucleus and initiated the transcription of downstream antioxidant factors, thereby relieving oxidative stress induced by a high-fat diet and lowering oxidative damage to the liver. Such results imply that the administration of STE can be regarded as a viable treatment option for NAFLD, providing a mechanism that can regulate the AMPK and Nrf2 signaling pathways.

Uncovering SOD3 and GPX4 as new targets of Benzo[α]pyrene-induced hepatotoxicity through Metabolomics and Chemical Proteomics

Benzo[α]pyrene (Bap) is recognized as a ubiquitous environmental pollutant among the polycyclic aromatic hydrocarbons (PAHs) class. Previous studies have shown that the hepatotoxicity of Bap is mainly caused by its metabolites, although it remains unclear whether Bap itself induces such damage. This study integrated metabolomics and chemical proteomics approaches to comprehensively identify the potential target proteins affected by Bap in liver cells. The results from the metabolomics showed that the significant changed metabolites were related with cellular redox homeostasis. CEllular Thermal Shift Assay (CETSA) showed that Bap induced protein thermal displacement of superoxide dismutase 3 (SOD3) and glutathione peroxidase 4 (GPX4), which are closely related to oxidative homeostasis. Further validation through in vitro CETSA and drug affinity response target stability (DARTS) revealed that Bap directly affected the stability of SOD3 and GPX4 proteins. The binding affinities of Bap to the potential target proteins were further evaluated using molecular docking, while the isothermal titration calorimetry (ITC) interaction measurements indicated nanomolar-level Kd values. Importantly, we found that Bap weakened the antioxidant capacity by destroying the activities of SOD3 and GPX4, which provided a new understanding of the mechanism of hepatotoxicity induced by Bap. Moreover, our provided workflow integrating metabolomics and label-free chemical proteomics, can be regarded as a practical way to identify the targets and inter-mechanisms for the various environmental compounds.

First comparison of early post-mortem proteomes in two goat muscle types: M. Longissimus thoracis and M. semitendinosus

This study aimed to characterize and compare the muscle proteomes of goat Longissimus thoracis (LT) and Semitendinosus (ST) muscles taken early post-mortem from young crossbred males. Thanks to a quantitative proteomics approach, 129 differentially expressed proteins (DEPs) were identified. The proteins belong to five interconnected biological pathways: muscle contraction and structure (n = 47), catalytic, metabolism & ATP processes (n = 33), binding and transport (n = 23), oxidative stress and cell redox homeostasis (n = 10), response to stress and protein folding (n = 6). An additional group of miscellaneous proteins (n = 10) grouped proteins playing other functions. The chemometrics analyses allowed clear separations of the muscles and evidenced 14 common proteins (ACTB, ACTN3, TMOD4, TPM3, TNNT1, AK1, AKR1B1, ACAA2, GPI, AGL, DNPEP, RTN4, ATP2A1, and CAVIN4) that could be considered as potential biomarkers. Overall, the study provided the first insights on the differences between goat LT and ST muscles and the basis related to the regulation of the skeletal muscle. Moreover, it resulted that a better understanding of the muscle characteristics would help in developing practices/processes to monitor meat quality and reduce the variations in fresh quality of meat, aged meat, and/or processed goat meat products.

SAT070 The G Protein Coupled Receptor GPR31 Promotes Islet Inflammation And Diabetes

Abstract Disclosure: C. Checkcinco: None. S.A. Tersey: None. R.G. Mirmira: None. In type 1 diabetes a characteristic immune response targets insulin secreting beta cells in pancreatic islets, resulting in their destruction. This pathogenesis features inflammatory signaling cascades in both beta cells and infiltrating immune cell macrophages. 12-Lipoxygenase (12-LOX) contributes to inflammation in β cells and macrophages by producing the eicosanoid 12-HETE, which induces oxidative and ER stress resulting in cellular dysfunction. G-protein coupled receptor 31 (GPR31) was identified as a high affinity 12-HETE receptor and is increased in human islets after cytokine induced inflammation, but it remains unknown if GPR31 might mediate the downstream effects of 12-LOX. We found increased expression of GPR31 in C57Bl/6J islets, over 7 times higher relative to macrophages. To investigate the role of GPR31 during diabetic inflammation, whole body GPR31 knockout mice were generated on the C57Bl/6J background and studied for glucose homeostasis in the setting of diabetic inflammation. Islets and macrophages from these mice were studied following manipulations in vitro. Compared to wildtype (WT) littermates, Gpr31b-/- mice maintained similar body weight, beta-cell mass, and glucose homeostasis as mice aged. To mimic the setting of islet inflammation as seen in type 1 diabetes, WT and Gpr31b-/- mice were treated with the pro-diabetic toxin streptozotocin (which induces beta cell death and macrophage influx). Compared to WT, Gpr31b-/- mice showed protection from development of hyperglycemia and glucose tolerance tests showed >30% protection reduction in area-under-the-curve, suggesting that GPR31 promotes islet dysfunction and hyperglycemia. To interrogate the role of GPR31 in the beta cell, we isolated islets from WT and Gpr31b-/- mice and treated them with proinflammatory cytokines followed by RNA sequencing to interrogate gene expression pathways. Differentially expressed genes in Gpr31b-/- islets included those pertaining to oxidative stress, MAPK signaling, and cellular homeostasis by Wnt/β-catenin, a finding reminiscent of pathways that are also altered following 12-LOX inhibition. To assess how GPR31 might impact macrophage function, we induced proinflammatory M1 polarization by lipopolysaccharide and interferon gamma in bone marrow-derived macrophages. We saw no significant difference in the extent of M1 polarization between GPR31b-/- and WT macrophages by flow cytometry, as assessed by the production of iNOS. We then asked if GPR31 was involved in the mobility of macrophages using a transwell assay with chemoattractant. We saw a ∼50% reduction in migrating bone marrow-derived macrophages in GPR31b-/- compared to WT. Taken together, these data are consistent with our previously published data on the 12-LOX knockout mice, suggesting that GPR31 may be involved in mediating the proinflammatory responses of 12-HETE in both β cells and macrophages. Presentation: Saturday, June 17, 2023

Effect of mode of delivery on neonatal oxidative stress and dynamic thiol-disulfide homeostasis.

To evaluate the effect of the mode of delivery on neonatal oxidative stress and dynamic thiol-disulfide homeostasis. Sixty women who were followed up in the Obstetrics and Gynecology clinic were included in this prospective study. Cord blood samples were obtained from women who underwent cesarean section (CS) and vaginal delivery (VD). Total oxidant status and total antioxidant status levels were measured by spectrophotometry. The dynamic thiol-disulfide balance was determined by colorimetry. The total antioxidant status and oxidative stress index levels were higher and total oxidant status levels were lower in the VD group compared with the CS group. Native and total thiol levels were higher while disulfide levels were lower in the VD compared with the CS delivery group, while disulfide levels were higher in the CS group. These results indicate that disulfide formation leads to decreased antioxidant capacity in women undergoing CS. Monitoring of dynamic thiol-disulfide levels may thus provide clinicians with important information on the oxidative stress status in newborns.

Functional Association between Storage Protein Mobilization and Redox Signaling in Narrow-Leafed Lupin (Lupinus angustifolius L.) Seed Germination and Seedling Development.

(1) Background: Seed storage mobilization, together with oxidative metabolism, with the ascorbate-glutathione (AsA-GSH) cycle as a crucial signaling and metabolic functional crossroad, is one of the main regulators of the control of cell morphogenesis and division, a fundamental physiological process driving seed germination and seedling growth. This study aims to characterize the cellular changes, composition, and patterns of the protein mobilization and ROS-dependent gene expression of redox metabolism in Lupinus angustifolius L. (narrow-leafed lupin, NLL) cotyledons during seed germination. (2) Methods: We performed gene expression analyses via RT-qPCR for conglutins α (1, 2, and 3), β (1, 2, and 5), γ (1, 2), and δ (2 and 4), including a ubiquitin gene as a control, and for redox metabolism-related genes; GADPH was used as a control gene. A microscopic study was developed on cotyledon samples from different germination stages, including as IMB (imbibition), and 2-5, 7, 9, and 11 DAI (days after imbibition), which were processed for light microscopy. SDS-PAGE and immunocytochemistry assays were performed using an anti-β-conglutin antibody (Agrisera), and an anti-rabbit IgG Daylight 488-conjugated secondary antibody. The controls were made while omitting primary Ab. (3) Results and Discussion: Our results showed that a large amount of seed storage protein (SSP) accumulates in protein bodies (PBs) and mobilizes during germination. Families of conglutins (β and γ) may play important roles as functional and signaling molecules, beyond the storage function, at intermediate steps of the seed germination process. In this regard, metabolic activities are closely associated with the regulation of oxidative homeostasis through AsA-GSH activities (γ-L-Glutamyl-L-cysteine synthetase, NOS, Catalase, Cu/Zn-SOD, GPx, GR, GS, GsT) after the imbibition of NLL mature seeds, metabolism activation, and dormancy breakage, which are key molecular and regulatory signaling pathways with particular importance in morphogenesis and developmental processes. (4) Conclusions: The knowledge generated in this study provides evidence for the functional changes and cellular tightly regulated events occurring in the NLL seed cotyledon, orchestrated by the oxidative-related metabolic machinery involved in seed germination advancement.

Flavonoid compound from Agrimonia pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation

BackgroundResearches and practice of traditional Chinese medicine indicated that Agrimonia pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). To reveal its underling mechanisms, we isolated Flavonoid component (FC) from Agrimonia pilosa Ledeb and elucidated its effects on glucose metabolism to improve IR by suppressing oxidative stress and inflammation.MethodsAdipocytes or mice IR model was established with overdosed glucose and insulin or high-fat diet. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, and superoxide dismutase (SOD) activity as well as the malondialdehyde (MDA) content were also measured. Meanwhile, factors associated with insulin signal pathway including PPARγ, insulin receptor substrate-1 (IRS-1), GLUT4, and oxidative stress including NF-E2-related factor 2 (Nrf2), as well as the related inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway was also explored.ResultsFC extracted from Agrimonia pilosa Ledeb ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could regulate the insulin signal pathway to improve insulin resistance. Moreover, it could upregulate PPARγ with the similar efficacy as pioglitazone (Piog) straightway. FC also decreased the endogenous ROS and MDA content, increased SOD activity and Nrf2 expression to facilitate oxidative homeostasis. It attenuated expression and secretion of inflammatory cytokines obviously. At last, our results indicated JNK/PI3K/Akt pathway was regulated by FC in adipocytes and adipose tissue.ConclusionFC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis-A Comprehensive One-Year Review.

Hydrogen sulfide (H2S), traditionally recognized as a toxic gas, has emerged as a critical regulator in many biological processes, including oxidative stress and cellular homeostasis. This review presents an exhaustive overview of the current understanding of H2S and its multifaceted role in mammalian cellular functioning and oxidative stress management. We delve into the biological sources and function of H2S, mechanisms underlying oxidative stress and cellular homeostasis, and the intricate relationships between these processes. We explore evidence from recent experimental and clinical studies, unraveling the intricate biochemical and molecular mechanisms dictating H2S's roles in modulating oxidative stress responses and maintaining cellular homeostasis. The clinical implications and therapeutic potential of H2S in conditions characterized by oxidative stress dysregulation and disrupted homeostasis are discussed, highlighting the emerging significance of H2S in health and disease. Finally, this review underscores current challenges, controversies, and future directions in the field, emphasizing the need for further research to harness H2S's potential as a therapeutic agent for diseases associated with oxidative stress and homeostatic imbalance. Through this review, we aim to emphasize H2S's pivotal role in cellular function, encouraging further exploration into this burgeoning area of research.

A Drosophila model of gestational antimony exposure uncovers growth and developmental disorders caused by disrupting oxidative stress homeostasis

The toxic heavy metal antimony (Sb) is ubiquitous in our daily lives. Various models have shown that Sb induces neuronal and reproductive toxicity. However, little is known about the developmental toxicity of Sb exposure during gestation and the underlying mechanisms. To study its effects on growth and development, Drosophila stages from eggs to pupae were exposed to different Sb concentrations (0, 0.3, 0.6 and 1.2 mg/mL Sb); RNA sequencing was used to identify the underlying mechanism. The model revealed that prenatal Sb exposure significantly reduced larval body size and weight, the pupation and eclosion rates, and the number of flies at all stages. With 1.2 mg/mL Sb exposure in 3rd instar larvae, 484 genes were upregulated and 694 downregulated compared to controls. Biological analysis showed that the disrupted transcripts were related to the oxidative stress pathway, as verified by reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and glutathione (GSH) intervention experiments. Sb exposure induced oxidative stress imbalance could be rectified by chelation and antioxidant effects of NAC/GSH. The Drosophila Schneider 2 (S2) model further demonstrated that NAC and GSH greatly ameliorated cell death induced by Sb exposure. In conclusion, gestational Sb exposure disrupted oxidative stress homeostasis, thereby impairing growth and development.

447 Haptoglobin Treatment to Improve Outcome After Aneurysmal Subarachnoid Haemorrhage: A Consensus Perspective on Clinical Translation

Abstract Aim Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of stroke with an unmet need to improve outcome. This study focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress and arriving at a Delphi-based global consensus regarding the role of extracellular haemoglobin and research priorities for clinical translation of haemoglobin-scavenging strategies. Method A narrative review of the topic by searching PubMed with relevant keywords and through discussions with leading expert in the field of aSAH. A modified Delphi processes. Four virtual meetings were held, two prior to starting, and two during the first round. Otherwise, the study was conducted electronically. Results Clinicians (n = 72) and scientific experts (n = 28) from five continents participated in the Delphi study. Microvascular spasm, iInflammation, microvascular spasm, and initial intracranial pressure rise were deemed the most important pathophysiological pathways determining outcome. Extracellular haemoglobin was thought to play an important role mostly in iron toxicity, oxidative stress, nitric oxide homeostasis and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field to be ready for early phase trial. The highest priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics and outcome measure selection. Conclusions These results highlight the pressing need for early phase trials of intracranial haptoglobin for aSAH, and the immense value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

Protective effects of Aureobasidium pullulans lysate on UV-damaged human skin fibroblasts and HaCaT cells

BackgroundAureobasidium pullulans (A. pullulans) has a wide range of applications. Ultraviolet (UV) rays from the sun can cause skin photoaging. In order to explore the protective effect and application potential of A. pullulans lysate on UV-damaged human skin fibroblasts (HSF) and HaCaT Cells, this study investigates the anti-aging and anti-inflammatory effects of A. pullulans lysate as well as the mechanism of anti-oxidative stress at the cellular and molecular levels through cytotoxicity experiments, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT-qPCR).ResultsThe experimental results have shown that the A. pullulans lysate can effectively reduce the loss of extracellular matrix components (EMC), such as collagen and hyaluronic acid (HA). It is also capable of scavenging excess reactive oxygen species (ROS) from the body, thereby increasing the activity of catalase, decreasing the overexpression of intracellular matrix metalloproteinases (MMPs), enhancing the gene expression of metalloproteinase inhibitors (TIMPs), and decreasing the level of inflammatory factors, reducing UV-induced apoptosis of HaCaT cells. Meanwhile, oxidative stress homeostasis is also regulated through the Nrf2/Keap1 and MAPK signaling pathways.ConclusionsThis study shows that the A. pullulans lysate has the potential to resist photoaging.Graphical

Differential oxidative stress homeostasis in two burley tobacco varieties is linked to different peroxisomal glycolate oxidase levels

Previous analyses of burley tobacco varieties KT 204LC and NCBH 129LC revealed that NCBH 129LC has a higher oxidative stress tolerance level and accumulates more hydrogen peroxide. We conducted untargeted metabolomics analyses to deepen our understanding of these varietal differences in redox status, and here, we show that KT 204LC and NCBH 129LC significantly differ in lipid metabolism, with NCBH 129LC containing more lipids than KT 204LC. Considering that NCBH 129LC also has more hydrogen peroxide and that peroxisomes play a major role in hydrogen peroxide production and lipid metabolism, we next analyzed peroxisomal markers. Glycolate oxidase, the key photorespiratory enzyme and a significant producer of hydrogen peroxide, accumulated significantly higher in NCBH 129LC. Our data suggest that differences in the oxidative stress status of burley varieties KT 204LC and NCBH 129LC are – at least partially - caused by different peroxisomal activities of the two varieties.

Prediction of protein aggregation propensity employing SqFt-based logistic regression model

Here we present a novel machine-learning approach to predict protein aggregation propensity (PAP) which is a key factor in the formation of amyloid fibrils based on logistic regression (LR). Amyloid fibrils are associated with various neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD), which are caused by oxidative stress and impaired protein homeostasis. Accordingly, the paper uses a dataset of hexapeptides with known aggregation tendencies and eight physiochemical features to train and test the LR model. Also, it evaluates the performance of the LR model using F-measure and Matthews correlation coefficient (MCC) as metrics and compares it with other existing methods. Moreover, it investigates the effect of combining sequence and feature information in the prediction. In conclusion, the LR model with sequence and feature information achieves high F-measure (0.841) and MCC (0.6692), outperforming other methods and demonstrating its efficiency and reliability for PAP prediction. In addition, the overall performance of the concluded method was higher than the other known servers, for instance, Aggrescan, Metamyl, Foldamyloid, and PASTA 2.0. The LR model can be accessed at: https://github.com/KatherineEshari/Protein-aggregation-prediction.

Sterol Regulatory Element-Binding Protein, BbSre1, Controls Oxidative Stress Response, Peroxisome Division, and Lipid Homeostasis in an Insect Fungal Pathogen.

Sterol regulatory element-binding protein, Sre1, regulates sterol biosynthesis, lipid metabolism, hypoxia adaptation, and virulence in some fungi, even though its roles are varied in fungal species. However, few studies report its other functions in fungi. Here, we report novel roles of Sre1 homolog, BbSre1, in the insect fungal pathogen, Beauveria bassiana, that regulates oxidative stress response, peroxisome division, and redox homeostasis. The gene disruption stain showed increased sensitivity to oxidative stress, which was in line with oxidative stress-induced-BbSre1 nuclear import and control of antioxidant and detoxification-involved genes. The gene mutation also inhibited peroxisome division, affected redox homeostasis, and impaired lipid/fatty acid metabolism and sterol biosynthesis, which was verified by downregulation of their associated genes. These data broaden our understanding of role of Sre1, which regulates peroxisome division, antioxidant, and detoxification-involved genes for control of redox homeostasis and oxidative stress response that links to lipid/fatty acid metabolism and sterol biosynthesis.

Neuroprotection and NRF2 signaling cascade analysis of new synthetic cinnamic acid-Eugenol hybrids

Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer's, Parkinson's, and Huntington's. NRF2 is a protein that regulates the expression of genes involved in antioxidant defense, detoxification, and other cellular processes that protect against oxidative damage and cellular homeostasis. This study looked at newly synthesized Cinnamic Acid-Eugenol hybrid derivatives and their effect on SH-SY5Y neurons under oxidative stress through the NRF2 signaling pathway. Derivatives were synthesized and confirmed through FT-IR, NMR, and Mass spectroscopy. Derivatives of Cinnamic Acid-Eugenol hybrid were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). Effects; on cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes measured after 24 h. Derivatives (A, B) were observed to enhance the viability of SH-SY5Y cells by defending against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as; NQO-1 and GSTK1.These study highlights that these derivatives demonstrated a neuroprotective action on SH-SY5Y cells through various neuroprotective mechanisms.