Oxidative Response Research Articles

Author Correction: Quantification of DNA double strand breaks and oxidation response in children and adults undergoing dental CBCT scan

Author Correction: Quantification of DNA double strand breaks and oxidation response in children and adults undergoing dental CBCT scan

Effects of MMP2 and its inhibitor TIMP2 on DNA damage, apoptosis and senescence of human lens epithelial cells induced by oxidative stress.

Oxidative stress-induced lens epithelial cells (LECs) death plays a pivotal role in pathogenesis of age-related cataract (ARC), causing significant visual impairment. Apoptosis of porcine granulosa cells mediated by MMP2 is linked to DNA damage. The current study aimed to investigate the potential mechanism of MMP2 in DNA damage, apoptosis and senescence of lens epithelial cells caused by oxidative stress. HLE-B3 cells were treated with different doses of H2O2 for 24h, and CCK-8 was used to detect cell viability. Furthermore, western blotting was used to detect the expressions of MMP2, Bcl2, Bax, cleaved caspase3, γ-H2AX, p16, p21, and TIMP2. DCFH-DA staining was used to assess ROS levels. Moreover, EdU staining was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. Then, 15A3 immunofluorescence staining and γ-H2AX staining were used to detect DNA damage. In addition, SA-β-gal staining was used to observe cell senescence. The present findings suggest that oxidative stress triggers damage to LECs viability and elevates the expression of MMP2. Furthermore, MMP2 interference attenuates H2O2-induced active damage, apoptosis, DNA damage, and cellular senescence in LECs. Additionally, TIMP2 expression is down-regulated in H2O2-induced LECs, which suppresses the expression of MMP2 induced by H2O2. These findings highlight the crucial role of MMP2 and TIMP2 in the modulation of oxidative stress-induced cellular responses in LECs. Collectively, TIMP2 alleviates H2O2-induced lens epithelial cell viability damage, apoptosis, DNA damage and cell senescence in LECs by inhibiting MMP2.

Tripartite Detection and Sensing of Toxic Heavy Metals Using a Copper-Based Porphyrin Metal-Organic Framework.

The detection of heavy metals in water sources is a critical concern for environmental preservation and public health. However, current electrochemical heavy metal sensors suffer from high sensing limits, cross-sensitivity, and poor selectivity. In this work, we present the possibility of an electrochemical sensor based on a copper (Cu) metal-organic framework for the detection of lead, cadmium, and mercury by replacing Cu metal nodes. The working electrode consists of a ∼5 μm thin layer of copper- tetracarboxyphenylporphyrin (Cu-TCPP) sheets that are adsorbed on a glassy carbon electrode (GCE). Upon interaction with Pb2+, Cd2+, and Hg2+, these ions are adsorbed on and incorporated into the metal nodes of the MOF. The adsorbed metallic species can be oxidized to the ionic form (Pb → Pb2+) electrochemically, which results in an oxidation response and enables the quantitative detection of these metals. The oxidation peak currents follow a (mostly) bimodal linear regression with a sensing range of up to 30 μM dependent on the deposition time and an ultralow limit of detection (LoD) of up to 5 nM. The system displays robust and selective sensing in saturated solutions of counterions and interfering metal ions (low error margins of <10%). This work represents the first report of a Cu-TCPP-modified GCE anode as an effective electrode for the sensitive detection of multiple heavy metals and an in-depth study into the Cu replacement kinetics of the Cu-MOF.

Exploring the mechanism of sesamin for the treatment of PM2.5-induced cardiomyocyte damage based on transcriptomics, network pharmacology and experimental verification

IntroductionExposure to fine particulate matter (PM2.5) is known to be associated with cardiovascular diseases. Sesamin (Ses) is a natural phenolic compound found in sesame seeds and sesame oil. Ferroptosis is a novel mode of cell death characterised by iron-dependent lipid peroxidation. This study aims to explore whether PM2.5 can induce ferroptosis in H9C2 cells and to investigate the precise protective mechanism of Ses.MethodsBased on transcriptomic data, PM2.5 may induce ferroptosis in cardiomyocytes. The ferroptosis inducer erastin and ferroptosis inhibitor ferrostatin-1 (Fer-1) were used to illustrate the mechanisms involved in PM2.5-induced H9C2 cell injury. Using network pharmacology, the pharmacological mechanism and potential therapy targets of Ses were explored for the treatment of PM2.5-induced cardiomyocyte injury. H9C2 cells were cultured and pretreated with Fer-1 or different concentrations of Ses, and then cardiomyocyte injury model was established using erastin or PM2.5. Indicators of oxidative responses, including total superoxide dismutase, reduced glutathione, glutathione peroxidase and malondialdehyde, were measured. The expression levels of ferroptosis-related proteins were determined through Western blot analysis.ResultsResults demonstrate that PM2.5 induces ferroptosis in H9C2 cells and Ses exerts a protective effect by suppressing ACSL4-mediated ferroptosis.DiscussionOverall, these findings elucidate a novel mechanism by which Ses ameliorates the detrimental effects of PM2.5 on cardiomyocytes.

Resveratrol attenuates Cr(VI)-induced disorders of glycolipid metabolism by regulating HNF1b/GPX1 in mice.

Epidemiological studies have indicated that exposure to hexavalent chromium (Cr(VI)) is associated with increased morbidity in the population. Resveratrol (Res) is a polyphenolic compound known for its role in mitigating oxidative stress and inflammation. In this study, we investigated the effects of resveratrol on Cr(VI)-induced disorders of glycolipid metabolism and elucidated its mechanisms. Male C57BL/6 mice were exposed to resveratrol and Cr(VI) for 45 days. Cr(VI) exposure led to elevated blood glucose levels, impaired glucose tolerance and insulin resistance, oxidative and inflammatory responses, and alterations in glycolipid metabolism molecules such as PCK1 and SREBP1, along with inhibition of HNF1b and GPX1. Resveratrol pretreatment increased the expression of HNF1b and GPX1, reduced oxidative and inflammatory responses, and ultimately ameliorated Cr(VI)-induced glycolipid metabolism disorders. These findings suggest potential new targets for the prevention and treatment of dysglycolipidosis.

Antipsychotic-Treated Schizophrenia Patients Develop Inflammatory and Oxidative Responses Independently From Obesity: However, Metabolic Disturbances Arise From Schizophrenia-Related Obesity.

To define the impact of obesity on inflammatory and oxidative disturbances in antipsychotic-treated schizophrenia patients. Several cytokines, inflammatory, metabolic, and oxidative status markers were evaluated in obese (n=40) and non-obese (n=40) antipsychotic-treated patients and compared with age-and BMI-matched controls (n=80). Schizophreniapatients had higher leptin, TNF-α, adiponectin, visfatin, resistin, P-selectin, NPY, BDNF, CD40-L, MCP-1, and malondialdehyde, and lower IL-6, ghrelin, neopterin, and vitamin E levels compared to their respective controls (p<0.001). Total oxidant status was higher in non-obese patients compared to controls (p<0.001), total antioxidant capacity was higher in obese compared to non-obese patients (p<0.01), but vitamin A and paraoxonase levels were not different. High sensitive-CRP levels were higher in obsese controls relative to non-obese controls (p<0.05) and in obese patients relative to non-obese patients (p<0.001). Fasting glucose, insulin, HbA1c, HOMA-IR, uric acid, total cholesterol, and triglyceride concentrations were higher in obese patients compared to non-obese patients. Insulin concentrations and HOMA-IR were also higher in obese controls than in non-obese controls. Our results suggest that inflammatory responses and oxidative stress develop independently from obesity in antipsychotic-treated schizophrenia patients. However, schizophrenia-induced obesity causes metabolic disturbances; thereby, obese schizophrenia patients are more liable to cardiovascular events and progress of metabolic syndrome than non-obese patients.

Repurposing Aprepitant: Can it protect against doxorubicin-induced Chemobrain beyond its antiemetic role?

The substance P (SP) and neurokinin-1 receptor (NK-1R) axis is crucial in numerous pathological processes, including inflammation, stress responses, pain perception, and vomiting. Consequently, aprepitant, an NK-1R blocker, is used as an antiemetic in chemotherapy, including the use of doxorubicin (DOX), but whether aprepitant can also assuage DOX-mediated chemobrain remains to be unveiled. Here, we scrutinized the potential neuroprotective effect and underlying mechanisms of aprepitant using DOX-induced chemobrain model, where rats were allocated into 4 groups (control, aprepitant, DOX, and DOX+ aprepitant). Cognitive deficits were assessed through behavioral tests and hippocampal structural alterations were determined by H&E and toluidine blue staining. Biochemical measurements were performed using ELISA, real-time quantitative PCR, western blotting, and immunohistochemical methods. Aprepitant improved cognitive responses, and hippocampal morphology, enhancing the presence of intact neurons. At the molecular tier, aprepitant significantly reduced hippocampal contents of SP and the inflammatory markers NF-κB and IL-1β. Additionally, it signified its antioxidant and antiapoptotic capacities by downregulating cleaved caspase-3 protein expression and curbing the content of malondialdehyde but boosted those of glutathione and Bcl-2. Aprepitant also downregulated the expression of miR-146a and turned off the endoplasmic reticulum (ER) stress cascade PERK/eIF-2α/ATF-4/CHOP. To recapitulate, aprepitant demonstrates a neuroprotective effect against DOX-mediated chemobrain by alleviating inflammatory, oxidative, and apoptotic responses, partly by reducing SP, ER stress, and miR-146a. These findings not only underscore the potential of aprepitant as a neuroprotective agent but also offer new understanding of the mechanisms behind chemobrain, leading to better therapeutic strategies for cancer patients.

High‐Temperature Oxidation Response of 444 Ferritic Stainless Steel in a Synthetic Automotive Exhaust Gas

The high‐temperature oxidation behavior of 444 ferritic stainless steel has been studied in cyclic oxidation experiments using synthetic automotive exhaust gas atmospheres at 950 and 1050 °C. The weight gain per unit area of the 444 ferritic stainless steel following oxidation at 950 °C for 100 h iss 85.7% lower than recorded at 1050 °C. The oxide scale at both temperatures consisted of Fe–Cr and Mn–Cr spinels in the outer layer and Cr2O3 in the inner layer. Nodule formation and spallation of the oxide scale are identified as the main causes of breakaway oxidation. The depth of the internal oxides gradually increases with the oxidation time. The nucleation and growth of internal SiO2 result in the formation of metal protrusions, which are eventually consumed in the formation of a SiO2 layer. The SiO2 layer is formed at the interface between the oxide scale and the substrate at 1050 °C. The nucleation and growth of internal SiO2, in combination with lateral growth of SiO2 at the Cr2O3 layer/substrate interface contributed to the formation of the SiO2 layer.

Electrochemical Oxidation of Glyphosate Using Graphite Rod Electrodes: Impact of Acetic Acid Pretreatment on Degradation Efficiency

The uncontrolled use of herbicides such as glyphosate (GLY) (N-phosphonomethylglycine) in agricultural production has resulted in its presence in water bodies and in negative impacts on the environment and public health. On the frame of understanding the interaction between GLY and graphite rod surfaces, this contribution relies on the study of electrochemical responses of different GLY concentrations by cyclic voltammetry under both open and closed-circuit conditions. Furthermore, the effect of the electrodes’ electrochemical pretreatment with acetic acid on the double-layer capacitance and the subsequent surface functionalization of the graphite rod materials were evaluated. The increment in GLY concentration showed a decrease in the electrochemical oxidation response associated with the adsorption of the contaminant on the surface of the graphite rod electrode and the concomitant blockage of the active sites. Electrochemical pretreatment of the electrodes with acetic acid and GLY concentration play crucial roles in electric double-layer formation due to their ability to interact with both positive and negative electrical charges. By means of optical microscope observations and Fourier Transform Infrared Spectroscopy analysis, it was possible to detect the formation of oxygenated functional groups on the electrode surfaces after the electrochemical pretreatment. Through a 23 factorial design analysis in repetition, the factors significant in the degradation of GLY were identified. The high degradation of GLY with the pretreated electrodes can be attributed to the preferential adsorption of the zwitterionic molecule at the interface, which allowed great direct oxidation of the contaminant on the anode’s surface.

Combined Restraint Stress and Metal Exposure Paradigms in Rats: Unravelling Behavioural and Neurochemical Perturbations.

Accumulation of heavy metals (Mn and Ni) and prolonged exposure to stress are associated with adverse health outcomes. Various studies have shown the impacts of stress and metal exposures on brain function. However, no study has examined the effects of co-exposure to stress, Mn, and Ni on the brain. This study addresses this gap by evaluating oxidative and glial responses, apoptotic activity, as well as cognitive processes in a rat model. Adult Wistar rats were exposed to vehicle (control), restraint stress, 25mg/kg of manganese (Mn) or nickel (Ni), or combined restraint stress plus Mn or Ni. Following treatment, rats were subjected to several behavioural paradigms to assess cognitive function. Enzyme activity, as well as ATPase levels, were evaluated. Thereafter, an immunohistochemical procedure was utilised to evaluate neurochemical markers of glial function, myelination, oxidative stress, and apoptosis in the hippocampus, prefrontal cortex (PFC), and striatum. Results showed that stress and metal exposure increased oxidative stress markers and reduced antioxidant levels. Further, combined stress and metal exposure reduced various forms of learning and memory ability in rats. In addition, there were alterations in Iba1 activity and Nrf2 levels, reduced Olig2 and myelin basic protein (MBP) levels, and increased caspase-3 expression. These neurotoxic outcomes were mostly exacerbated by co-exposure to stress and metals. Overall, our findings establish that stress and metal exposures impaired cognitive performance, induced oxidative stress and apoptosis, and led to demyelination effects which were worsened by combined stress and metal exposure.

The de-sulfinylation enzyme sulfiredoxin-1 attenuates hepatic stellate cell activation and liver fibrosis by modulating the PTPN12-NLRP3 axis.

Liver fibrosis is characterized by the progressive scarring of liver tissue. Oxidative stress is a critical causal factor of hepatic stellate cell (HSC) activation and the subsequent liver fibrogenesis, but the mechanism is not fully understood. Cysteine sulfinic acid (Cys-SO2H), a modification of reactive cysteine residues, is a unique form of oxidative response that alters the structure and function of proteins. Sulfiredoxin 1 (SRXN1) is responsible for ATP-dependent reduction of the Cys-SO2H to sulfenic acid (Cys-SOH). We found that the expression of SRXN1 was increased in activated HSCs and in human and mouse fibrotic livers. HSC-specific ablation of Srxn1 or pharmacological inhibition of Srxn1 exacerbated HSC activation and sensitized mice to liver fibrosis. Mechanistically, SRXN1 inhibited HSC activation by de-sulfinylating the phosphatase protein tyrosine phosphatase non-receptor type 12 (PTPN12), which enhanced its phosphatase activity and protein stability, leading to decreased tyrosine phosphorylation and reduced activation of the pro-fibrotic inflammasome protein NLRP3. The anti-fibrotic effect of SRXN1 was abolished when NLRP3 was inhibited. In contrast, overexpression of PTPN12 attenuated NLRP3 activation, and this effect was further amplified by the C164A S-sulfinylation resistant mutant of PTPN12. Our findings have uncovered an important role of SRXN1 and protein S-sulfinylation in HSC activation and liver fibrosis. The SRXN1-PTPN12-NLRP3 axis represents potential therapeutic targets for liver fibrosis.

Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes.

Excessive oxidative response, unbalanced immunomodulation, and impaired mesenchymal stem cell function in periodontitis in diabetes makes it a great challenge to achieve integrated periodontal tissue regeneration. Here, a polyphenol-mediated redox-active algin/gelatin hydrogel encapsulating a conductive poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber network and a hydrogen sulfide sustained-release system utilizing bovine serum albumin nanoparticles is developed. This hydrogel is found to reverse the hyperglycemic inflammatory microenvironment and enhance functional tissue regeneration in diabeticperiodontitis. Polydopamine confers the hydrogel with anti-oxidative and anti-inflammatory activity. Theslow, sustained release of hydrogen sulfide from the bovine serum albumin nanoparticles recruits mesenchymal stem cells and promotes subsequent angiogenesis and osteogenesis. Moreover, poly(3,4-ethylenedioxythiopene)-assembled polydopamine-mediated silk microfiber confers the hydrogel with good conductivity, which enables it to transmit endogenous bioelectricity, promote cell arrangement, and increase the inflow of calcium ion. In addition, the synergistic effects of hydrogen sulfide gaseous-bioelectric coupling promotes bone formation by amplifying autophagy in periodontal ligament stem cells and modulating macrophage polarization via lipid metabolism regulation. This study provides innovative insights into the synergistic effects of conductivity, reactive oxygen species scavenging, and hydrogen sulfide on the periodontium in a hyperglycemic inflammatory microenvironment, offering a strategy for the design of gaseous-bioelectric biomaterials to promote functional tissue regeneration in immune-related diseases.

Microplastics–biofilm in aquatic ecosystem: Formation, pollutants complexation, greenhouse gas emission and ecotoxicology

The omnipresent microplastics (MPs) have gradually become a significant environmental problem due to its adverse consequences for ecological systems. MPs serve as substrates for biofilms colonization, which enhances adsorption of harmful contaminants on MPs surface in the aquatic ecosystem. The present study provides a critical discussion on the mechanism involved in MPs–biofilm formation, microbial colonization and the robust factors influencing the process in the aquatic ecosystem. Subsequently, the impact of MPs–biofilm on adsorption of inorganic and organic contaminants is explored. The ecological significance of MPs–biofilm associated pollutant complex for promoting greenhouse gases (GHGs) emissions from aquatic ecosystem is extensively discussed for understanding the climatic risk. Furthermore, the discussion is extended over ecotoxicological impact of MPs–biofilm on aquatic biodiversity and humans. The protective extracellular polymeric substances secreted by colonised bacteria over MPs during biofilm formation creates sticky MPs surface for heteroaggregates formation with swift adsorption of chemical compounds and microorganisms. MPs with functional aromatic groups facilitate the bacterial adhesion on the surface, but affect formation of biofilm. Alternatively, MPs–biofilm promotes the Mn and Fe hydrous oxides formation that can co–precipitate with heavy metal ions and facilitate in remediation measures. However, MPs biodegradation generates GHGs emission per unit mass, comparably more from freshwater than marine ecosystem. Considering the toxicity, MPs–biofilm induces the oxidative response in fishes, causing painful death and thus, destroys aquatic biodiversity. This study will be useful to address MPs–biofilm associated pollution scenario via trace, test and treat strategy involving future engineering research framework for ecological restoration.

Dysfunctional copper homeostasis in Caenorhabditis elegans affects genomic and neuronal stability

While copper (Cu) is an essential trace element for biological systems due to its redox properties, excess levels may lead to adverse effects partly due to overproduction of reactive species. Thus, a tightly regulated Cu homeostasis is crucial for health. Cu dyshomeostasis and elevated labile Cu levels are associated with oxidative stress and neurodegenerative disorders, but the underlying mechanisms have yet to be fully characterized. Here, we used Caenorhabditis elegans loss-of-function mutants of the Cu chaperone ortholog atox-1 and the Cu binding protein ortholog ceruloplasmin to model Cu dyshomeostasis, as they display a shifted ratio of total Cu towards labile Cu. We applied highly selective and sensitive techniques to quantify metabolites associated to oxidative stress with focus on mitochondrial integrity, oxidative DNA damage and neurodegeneration all in the context of a disrupted Cu homeostasis. Our novel data reveal elevated oxidative stress, compromised mitochondria displaying reduced ATP levels and cardiolipin content. Cu dyshomeostasis further induced oxidative DNA damage and impaired DNA damage response as well as neurodegeneration characterized by behavior and neurotransmitter analysis. Our study underscores the essentiality of a tightly regulated Cu homeostasis as well as mitochondrial integrity for both genomic and neuronal stability.

Mechanisms of Lung Endothelial Cell Injury and Survival in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, chronic, and incurable inflammatory pulmonary vascular disease characterized by significant sex bias and largely unexplored microbial-associated molecular mechanisms that may influence its development and sex prevalence across various subgroups. PAH can be subclassified as idiopathic, heritable, or associated with conditions such as connective tissue diseases, congenital heart defects, liver disease, infections, and chronic exposure to drugs or toxins. During PAH progression, lung vascular endothelial cells (ECs) undergo dramatic morphofunctional transformations in response to acute and chronic inflammation. These transformations include the appearance and expansion of abnormal vascular cell phenotypes such as those derived from apoptosis-resistant cell growth and endothelial-to-mesenchymal transition (EndoMT). Compelling evidence indicates that these endothelial phenotypes seem to be triggered by chronic lung vascular injury and dysfunction, often characterized by reduced secretion of vasoactive molecules like nitric oxide (NO) and exacerbated response to vasoconstrictors such as Endothelin-1 (ET-1); both long-term known contributors of PAH pathogenesis. This review sheds light on the mechanisms of EC dysfunction, apoptosis, and EndoMT in PAH, aiming to unravel the intricate interactions between ECs, pathogens, and other cell types that drive the onset and progression of this devastating disease. Ultimately, we hope to provide an overview of the complex functions of lung vascular ECs in PAH, inspiring novel therapeutic strategies that target these dysfunctional cells to improve the treatment landscape for PAH, particularly in the face of current and emerging global pathogenic threats.

Photophysiological and Oxidative Responses of the Symbiotic Estuarine Anemone Anthopleura hermaphroditica to the Impact of UV Radiation and Salinity: Field and Laboratory Approaches.

The estuarine anemone Anthopleura hermaphroditica and its symbiont Philozoon anthopleurum are continuously exposed to intense fluctuations in solar radiation and salinity owing to tidal changes. The aim of this study was to evaluate the effects of the tidal cycle, solar radiation, and salinity fluctuations on the photosynthetic and cellular responses (lipid peroxidation, total phenolic compounds, and antioxidant activity) of the symbiont complex over a 24 h period in the Quempillén River Estuary. Additionally, laboratory experiments were conducted to determine the specific photobiological responses to photosynthetically active radiation (PAR), ultraviolet radiation (UVR), and salinity. Our field results showed that the photosynthetic parameters of the symbiont complex decreased with increasing ambient radiation; however, no relationship was observed with changes in salinity. Increased peroxidative damage, total phenolic compound levels, and antioxidant activity were mainly related to increased UVR and, to a lesser extent, PAR. During the dark period, only PAR-exposed organisms returned to the basal levels of photosynthesis and cell damage. Laboratory exposure confirmed the deleterious effects of UVR on the photosynthetic response. The present study suggests that the ability of A. hermaphroditica to acclimate to natural radiation stress is mediated by the concerted action of various physiological mechanisms that occur at different times of the day, under varying levels of environmental stress.

Graphenic materials prepared from magnesium ions doping cellulose and its application in electrochemical detection of adenine and guanine

Graphenic materials of high quality are in high-demand. In this study, a method is proposed for the synthesis of graphenic materials by the pyrolysis of cellulose materials. Cellulose materials were oxidized and doped with magnesium prior to pyrolysis, which improved the graphitization efficiency significantly. The obtained graphenic materials, exhibiting a well-developed porous structure, high specific surface area, were employed for the fabrication of a composite electrode. The composite electrode was employed for the simultaneously detection of adenine (AE) and guanine (GA) with excellent performance in the electrocatalytic oxidation response. Various electrochemical tests were carried out to optimized the detection of AE and GA. Under the optimized conditions, the simultaneous quantification of GA and AE is achieved from 1 – 100 μM with detection limits from 0.4 – 0.6 μM. This study offers a promising alternative for the synthesis of graphenic materials of high quality.

Anti-oxidant, anti-apoptotic and anti-inflammatory effects of geraniin in spinal cord injury in rat: role of COX-2.

Spinal cord injury (SCI) is devastating diseases affecting the degeneration of the spinal column, and vascular problems. However, the currently available therapeutic interventions are insufficient to address the effect of SCI which leads to significant impact on the morbidity and mortality of patients. In the present manuscript, we intend to investigate the pharmacological effect of geraniin on the SCI in Sprague-Dawley (SD) rats. The SCI in rats were induced by the conventional weight-drop method and treated with GER (2.5, 5, and 10 mg/kg). Subsequently, the locomotor activity of rats with SCI was assessed using Basso, Beattie, and Bresnahan (BBB) scores, while oxidative stress indicators and inflammatory variables were analyzed using commercially available kits. Additionally, neuronal death was quantified using TUNEL labeling. The enzymatic activity of caspase 3, 8, and 9 was also assessed. Furthermore, the expression levels of Bcl2, Bax, and COX-2 in rat spinal cords after SCI were analyzed by RT-PCR analysis. Our research indicated that therapy with GER in a manner that depends on the dosage could enhance the functional recovery, as well as reduce the occurrence of apoptosis, mitigate the inflammatory and oxidative response in rats with SCI. Furthermore, it was observed that GER increased the expression of Bcl2 and decreased the expression of Bax and COX-2. The concentration of caspase-3, -8, and -9 was observed to be decreased in SCI rats treated with GER. GER might protect the spinal cord from SCI by reducing apoptosis, oxidative stress, and inflammatory response through the inhibition of COX-2.

Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice.

Transforming growth factor (TGF)-β is up-regulated in the diabetic myocardium and may mediate fibroblast activation. We aimed at examining the role of TGF-β-induced fibroblast activation in the pathogenesis of diabetic cardiomyopathy. We generated lean and obese db/db mice with fibroblast-specific loss of TbR2, the Type 2 receptor-mediating signaling through all three TGF-β isoforms, and mice with fibroblast-specific Smad3 disruption. Systolic and diastolic function, myocardial fibrosis, and hypertrophy were assessed. Transcriptomic studies and in vitro experiments were used to dissect mechanisms of fibroblast activation. Fibroblast-specific TbR2 loss attenuated systolic and diastolic dysfunction in db/db mice. The protective effects of fibroblast TbR2 loss in db/db mice were associated with attenuated fibrosis and reduced cardiomyocyte hypertrophy, suggesting that in addition to their role in fibrous tissue deposition, TGF-β-stimulated fibroblasts may also exert paracrine actions on cardiomyocytes. Fibroblast-specific Smad3 loss phenocopied the protective effects of fibroblast TbR2 loss in db/db mice. Db/db fibroblasts had increased expression of genes associated with oxidative response (such as Fmo2, encoding flavin-containing monooxygenase 2), matricellular genes (such as Thbs4 and Fbln2), and Lox (encoding lysyl oxidase). Ingenuity pathway analysis (IPA) predicted that neurohumoral mediators, cytokines, and growth factors (such as AGT, TGFB1, and TNF) may serve as important upstream regulators of the transcriptomic profile of diabetic mouse fibroblasts. IPA of scRNA-seq data identified TGFB1, p53, MYC, PDGF-BB, EGFR, and WNT3A/CTNNB1 as important upstream regulators underlying fibroblast activation in db/db hearts. Comparison of the transcriptome of fibroblasts from db/db mice with fibroblast-specific Smad3 loss and db/db Smad3 fl/fl controls identified Thbs4 [encoding thrombospondin-4 (TSP-4), a marker of activated fibroblasts] as a candidate diabetes-induced fibrogenic mediator. However, in vitro experiments showed no significant activating effects of matricellular or intracellular TSP-4 on cardiac fibroblasts. Fibroblast-specific TGF-β/Smad3 signaling mediates ventricular fibrosis, hypertrophy, and dysfunction in Type 2 diabetes.

From landraces to haplotypes, exploiting a genomic and phenomic approach to identify heat tolerant genotypes within durum wheat landraces

Dry and hot climates severely impact wheat yields, necessitating the development of innovative solutions to accelerate the breeding and selection of more adaptable durum wheat genotypes. The aim of this study was to identify new wheat ecotypes that can bridge the gap between commercial varieties and adaptability to ongoing climate change. In this study, advanced genomic and phenomic techniques were combined to characterize a set of durum wheat landraces derived from single seed descent (SSD). This approach enabled the identification of novel variability in the TdHsp26-A1 and -B1 genes. As a result, 38 durum wheat genotypes were analyzed using targeted enrichment PCR, leading to the identification of 17 novel haplotype combinations with SNPs in the TdHsp26 genes. The response of these SSD haplotypes to heat stress was characterized at both the seedling and tillering growth stages. Phenotypic analysis of contrasting genotypes led to the selection of two distinct genotypes: SSD69 and SSD397. During heat stress, SSD69 exhibited altered accumulation of H2O2 and MDA content under both growth conditions, providing new insights into the oxidative response to heat stress. Additionally, this work identifies phenotypic traits that are suitable for detecting differences between variants. The geographic distribution of the different alleles aligned with the spread of durum wheat from its center of origin.