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The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.

Cryopreservation of sperm is an effective method for conserving germplasm resources in fish genetic breeding. The high-quality hybrid fish (WR) derived from white crucian carp (Carassius cuvieri, WCC, ♀) and red crucian carp (C. auratus red var., RCC, ♂), possesses valuable traits such as high survival rates, strong resistance, and rapid growth, representing an important germplasm resources of crucian carp. This study compared the effects of different antifreeze solutions on sperm viability among three varieties (WR, WCC, and RCC) and examined changes in enzyme activity, fertilization rates, and hatching rates after cryopreservation, aiming to enhance the cryogenic sperm cryopreservation technique in hybrid fish and investigate the mechanisms underlying spermatozoa damage caused by cryopreservation. The results showed that the antifreeze combination of D14 with 15 % dimethyl sulfoxide (DMSO) had the best effect in preserving the sperm of WR and WCC, while D20 with 10 % DMSO was the optimal combination for RCC sperm. After ultra-low temperature preservation, the longevity, fertilization, and hatching rates of frozen sperm were significantly lower (P < 0.05) compared to fresh sperm. The enzyme activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), and creatine kinase (CK) were significantly decreased (P < 0.05) in spermatozoa, whereas they showed a significant increase (P < 0.05) in sperm plasma. Succinate dehydrogenase (SDH) activity was significantly reduced (P < 0.05) in frozen spermatozoa of RCC compared to fresh spermatozoa, and exhibited lower activity in frozen spermatozoa of WCC and WR. Additionally, SDH activity was significantly elevated (P < 0.05) in frozen sperm plasma, and glutathione reductase (GR) activity was significantly lower (P < 0.05) in both frozen sperm plasma and spermatozoa across all three species. The study demonstrated that cryopreservation had a significant effect on the enzyme activities of spermatozoa and sperm plasma in all three species. These findings provide important technical support for the conservation of high-quality fish germplasm resources, particularly for novel varieties resulting from distant hybridization in fish. [ABSTRACT FROM AUTHOR]

Objectives Paragangliomas of the lateral skull base are rare, largely benign, neuroendocrine tumors. Little evidence exists to support clinicians in the management of these tumors. The present study evaluates considerations in the multidisciplinary workup and management of paragangliomas affecting the lateral skull base. Methods A STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist compliant retrospective review of adult patients with lateral skull base paragangliomas over 20 years (2002–2021) was performed. Patient and tumor data were collected from patient health care records. Results Seventy patients were identified including 21 (30.0%) males and 49 (70.0%) females. The mean length of follow-up was 87.3 months (range: 12–239 months). Twenty-nine (41.4%) patients had Fisch A or B tumors. Overall, 57 patients (81.4%) were offered treatment upfront, with 13 patients (18.6%) initially undergoing active surveillance. Younger age and reduced American Society of Anesthesiologists (ASA) grade was significantly associated with a decision to offer treatment at presentation (both p = 0.03), while all patients with succinate dehydrogenase (SDH) mutations (n = 10) and tumor secretion (n = 4) were offered treatment. Patients with Fisch A/B tumors (p = 0.01), cranial neuropathies (p = 0.01), and smaller tumors (p = 0.01) were more likely to undergo surgical resection. At the time of the last follow-up, the proportion of patients with a cranial neuropathy was notably lower in the observation (3/12, 25.0%) and radiotherapy (1/6, 16.7%) groups. Conclusion In our series, younger, fitter patients with SDH mutations, cranial neuropathies, or tumor secretion were more likely to be offered upfront treatment. There was a low incidence of new cranial neuropathy in the patients selected for observation during long-term follow-up. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare epithelial tumor with a biallelic mutation involving any subunit of the SDH complex. Mostly, it has low-grade morphology and a favorable prognosis. We present a case of a 36-year-old woman with weight loss, night sweats, and symptomatic anemia. Her imaging showed a hypo-enhancing heterogeneous right renal mass with invasion of the renal vein and inferior vena cava. Microscopically, the tumor had focal low-grade areas (5%) and extensive areas with high-grade features, including rhabdoid (85%) and sarcomatoid (10%) dedifferentiation. Cytoplasmic inclusions, foci of extracellular mucin, coagulative necrosis, and inflammatory infiltrate were present. The tumor cells, including rhabdoid differentiated, were focally positive for AE1/AE3. Tumor cells showed loss of SDHB immunostaining, consistent with diagnosis. Genetics testing was recommended, but the patient expired due to metastatic carcinoma. Prior studies suggest that sarcomatoid transformation and coagulative necrosis increase the risk of metastasis by up to 70% in SDH-deficient RCC. Follow-up with surveillance for other SDH-deficient neoplasms is recommended in cases of germline mutation. Here, we report the first case of SDH-deficient RCC with concomitant rhabdoid and sarcomatoid features and a detailed review of diagnostic difficulties associated with high-grade tumors. [ABSTRACT FROM AUTHOR]

Klebsiella aerogenes is an opportunistic nosocomial bacterial pathogen that commonly causes urinary tract infections. Over the past decades, K. aerogenes strains have acquired resistance to common antibiotics that has led to the rise of multidrug-resistant and even pandrug-resistant strains. Infections produced by these strains are nearly impossible to treat, which makes K. aerogenes a global priority to develop new antibiotics and there is an urgent need to identify targets to treat infections against this pathogen. However, very little is known about the metabolism and metabolic adaptations of this bacterium in infection sites. In this work, we investigated the respiratory metabolism of K. aerogenes in conditions that resemble human urine, allowing us to identify novel targets for antibiotic development. Here we describe that, unlike other gram-negative pathogens, K. aerogenes utilizes the type-2 NADH dehydrogenase (NDH-2) as the main entry point for electrons in the respiratory chain in all growth conditions evaluated. Additionally, in urine-like media, the aerobic metabolism as a whole is upregulated, with significant increases in succinate and lactate dehydrogenase activity. Moreover, our data show that the bd -I type oxidoreductases are the main terminal oxidases of this microorganism. Our findings support an initial identification of NDH-2 and bd -I oxidase as attractive targets for the development of new drugs against K. aerogenes as they are not found in human hosts. [ABSTRACT FROM AUTHOR]

Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct metabolic processes. Here, we identify succinate dehydrogenase (SDH) deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to various anti-cancer therapies. Mechanistically, succinate promotes the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function is mediated by succinate-triggered upregulation of ubiquitin-conjugating enzyme E2M (UBC12) phosphorylation, which impairs its E2 function in cullins neddylation. Notably, decreasing succinate by fludarabine can restore the sensitivity of anti-cancer drugs in SDH-deficient AML. Together, we uncover the function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML. The underlying mechanisms for drug resistance in Acute Myeloid Leukemia (AML) are not completely understood. Here, the authors show that succinate accumulation, associated with succinate dehydrogenase deficiency, impairs the activity of the ubiquitin-conjugating enzyme UBC12 leading to tumor-promoting protein accumulation and drug resistance in AML. [ABSTRACT FROM AUTHOR]

Background: Odontotermes formosanus (Shiraki) is a highly damaging agroforestry pest. Serratia marcescens is a broad-spectrum insecticidal pathogen and is highly lethal to O. formosanus. However, little is known about the mechanism between them. To improve the biological control of pests, a more in-depth analysis of the interactions between the pests and the pathogens is essential. Results: We used RNA-seq, enzyme activity assays and real-time fluorescent quantitative PCR (qPCR) to explore the defense responses of O. formosanus against SM1. RNA-seq results showed that 1,160, 2,531 and 4,536 genes were differentially expressed at 3, 6 and 12 h after SM1 infection, and Kyoto Encyclopedia of Genes and Genomes (KEGG) results indicated that immune response and energy metabolism were involved in the defense of O. formosanus against SM1. Reactive oxygen species (ROS) levels and ROS synthesis genes were significantly elevated, and the antioxidant system were induced in O. formosanus after SM1 infection. In addition, the cellular immune genes were affected, and the Toll, immune deficiency (Imd), Janus kinase/signal transducer and activator of transcription (JAK/STAT), c-Jun N-terminal Kinase (JNK) and melanization pathways were activated. In vitro, Oftermicin, an antimicrobial peptide, had a significantly inhibitory effect on SM1. Furthermore, the expression levels and enzyme activities of phosphofructokinase (PFK), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) in glycolysis and tricarboxylic acid (TCA) cycles were increased. Conclusions: Our results clearly demonstrated that O. formosanus defended against SM1 by activating the antioxidant system, innate immunity and energy metabolism. This study would provide useful information for the development of biological controls of O. formosanus. [ABSTRACT FROM AUTHOR]

Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyH C1 and MyHC2 a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production. [ABSTRACT FROM AUTHOR]

Melatonin treatment has been reported to effectively preserve and improve the postharvest quality of fruits and vegetables during storage. This research focused on examining the significance of melatonin on maintaining the quality of fresh Gastrodia elata tubers throughout the storage period. The findings demonstrated that melatonin application effectively reduced the deterioration rate and inhibited the rise in respiratory rate, malondialdehyde content, and weight loss, while slowing down the decline in soluble solid content. Melatonin treatment led to a decrease in hydrogen peroxide production and a rise in non-enzymatic antioxidant concentrations, including ascorbic acid. Furthermore, it boosted both the activity and expression of indispensable antioxidant enzymes, like superoxide dismutase, catalase, and ascorbate peroxidase. Additionally, melatonin treatment promoted the accumulation of total phenols, flavonoids, and lignin in fresh G. elata, while enhancing both the activity and expression of critical enzymes in the phenylpropanoid pathway, including phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate-CoA ligase. Moreover, melatonin treatment boosted the activity and expression of energy-associated enzymes including H+-ATPase, succinate dehydrogenase, Ca2+-ATPase, and cytochrome C oxidase, contributing to the improvement of energy levels in fresh G. elata. In summary, melatonin enhances the antioxidant potential and reduces oxidative damage in fresh G. elata by activating reactive oxygen species, phenylpropanoid metabolism, and energy metabolism, thereby maintaining its postharvest quality. [ABSTRACT FROM AUTHOR]

In light of the increasing water scarcity and the need for sustainable waste management, the use of landfill leachate for irrigation has emerged as both a solution and a concern, posing potential risks to soil health and plant vitality. This study examined the multifaceted impacts of leachate irrigation on the soil characteristics, plant growth, and enzymatic activities of Medicago sativa (M. sativa). By exposing alfalfa to different concentrations of leachate, we assessed the influence on heavy metal accumulation, physiological parameters, and enzyme functions. The physicochemical profile of the leachate indicated that the pH was within acceptable limits, but the chemical oxygen demand (COD), biochemical oxygen demand (BOD5), and concentrations of lead (Pb) and aluminum (Al) exceeded regulatory standards. Morphological parameters exhibited dual effects: stimulation at lower leachate doses and inhibition at higher leachate doses. Our findings show that soil acts as a buffer, reducing heavy metal uptake by plants. Enzymatic activities, including catalase, peroxidase, and succinate dehydrogenase, fluctuated significantly at higher leachate concentrations, indicating stress responses. This research underscores the interplay between leachate irrigation, plant physiology, and soil health, emphasizing sustainable management to optimize plant growth and minimize environmental impacts. It also stresses refining leachate application protocols to preserve soil and ecosystem health. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gray mold caused by Botrytis cinerea is one of the most serious diseases affecting strawberry. Succinate dehydrogenase inhibitor (SDHI) fungicides have been used for more than a decade to control the disease. Monitoring resistance and improving in‐depth understanding of resistance mechanisms are essential for the control of B. cinerea. RESULTS: In this study, resistance monitoring of a SDHI fungicide boscalid was conducted on B. cinerea isolated from strawberries in Korea during 2020 and 2021, with resistance rates of 76.92% and 72.25%, respectively. In resistant strains, mutations P225F/H and H272R were found in SdhB, with P225F representing the dominant mutation type. Simultaneous mutations G85A, I93V, M158V, and V168I in SdhC were detected in 54.84% of sensitive strains. Sensitivity profiles of different Sdh genotypes of B. cinerea strains to six SDHIs were determined in vitro and in vivo. In addition, the mutation(s) were genetically validated through in situ SdhB (SdhC) expression. Docking assays between SDHIs and AlphaFold model‐based Sdh complexes revealed generally consistent patterns with their in vitro phenotypes. CONCLUSION: Resistance of B. cinerea to SDHI fungicide on strawberry was systematically investigated in this study. Deciphering of SDHI resistance through the genetic transformation system and AlphaFold model‐based molecular docking will provide valuable insights into other target site‐based fungicide resistance in fungal pathogens. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Utilizing fungicides to protect crops from diseases is an effective method, and novel eco‐friendly plant‐derived fungicides with high efficiency and low toxicity are urgent requirements for sustainable crop protection. RESULT: Two series of rosin‐based fungicides (totally 35) were designed and synthesized. In vitro fungicidal activity revealed that Compound 6a (Co. 6a) effectively inhibited the growth of Valsa mali [median effective concentration (EC50) = 0.627 μg mL−1], and in vivo fungicidal activity suggested a significant protective efficacy of Co. 6a in protecting both apple branches (35.12% to 75.20%) and apples (75.86% to 90.82%). Quantum chemical calculations (via density functional theory) results indicated that the primary active site of Co. 6a lies in its amide structure. Mycelial morphology and physiology were investigated to elucidate the mode‐of‐action of Co. 6a, and suggested that Co. 6a produced significant cell membrane damage, accelerated electrolyte leakage, decreased succinate dehydrogenase (SDH) protein activity, and impaired physiological and biochemical functions, culminating in mycelial mortality. Molecular docking analysis revealed a robust binding energy (ΔE = −7.29 kcal mol−1) between Co. 6a and SDH. Subsequently, biosafety evaluations confirmed the environmentally‐friendly nature of Co. 6a via the zebrafish model, yet toxicological results indicated that Co. 6a at median lethal concentration [LC50(96)] damaged the gills, liver and intestines of zebrafish. CONCLUSION: The above research offers a theoretical foundation for exploiting eco‐friendly rosin‐based fungicidal candidates in sustainable crop protection. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Promiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)+-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism. Using adaptive laboratory evolution (ALE), we show that Sad can substitute for the roles of erythrose 4-phosphate dehydrogenase in pyridoxal 5'-phosphate (PLP) biosynthesis and glyceraldehyde 3-phosphate dehydrogenase in glycolysis. To recruit Sad for PLP biosynthesis and glycolysis, ALE employs various mechanisms, including active site mutation, copy number amplification, and (de)regulation of gene expression. Our study traces down these different evolutionary trajectories, reports on the surprising active site plasticity of Sad, identifies regulatory links in amino acid metabolism, and highlights the potential of an ordinary enzyme as innovation reservoir for evolution. Enzyme promiscuity seeds evolutionary innovation, but how flexible a single enzyme can be (re-)used during evolution remains unclear. Here, the authors show that various evolutionary trajectories applied to succinate semialdehyde dehydrogenase can compensate for the loss of two different functions in E. coli. [ABSTRACT FROM AUTHOR]

Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system. • Patients with major depressive disorder (MDD) exhibited lower cerebral hemodynamic responses to verbal fluency tests. • These reduced hemodynamic responses were associated with mitochondrial dysfunction, as indicated by lower levels of SDH protein. • Additionally, attenuated hemodynamic responses in the frontotemporal regions and decreased SDH levels were found to increase the risk for MDD. [ABSTRACT FROM AUTHOR]

Cercospora leaf blight (CLB) and purple seed stain (PSS) are major diseases of soybean responsible for significant yield loss. These diseases are caused by Cercospora species, such as C. kikuchii and C. cf. flagellaris, among the main species. These pathogens overwinter in infested debris and infected seed. Due to the combination of no‐till farming, monoculture in large soybean cultivation areas and climate changes, these diseases have become serious and prevalent. At present, in addition to the practice of monoculture soybean cultivation, there is a lack of soybean varieties with genetic resistance to these diseases. As a result, the application of fungicides becomes an essential tool for effectively managing this pathosystem. However, in the main soybean‐producing countries, resistance to quinone outside inhibitors and benzimidazole fungicides has already been studied and documented. Furthermore, Cercospora spp. are believed to be naturally insensitive to succinate dehydrogenase inhibitors. Consequently, there is a growing interest in innovative and integrated tools for managing crop diseases. These new approaches include the use of biofungicides, biostimulants and plant defence inducers. Research testing new management tools in a complementary and integrated approach involves a short‐term challenge to improve CLB/PSS management in the field. This review provides comprehensive details on the taxonomy, identification and genetic diversity of the pathogen, its disease symptoms and host range. Additionally, it outlines epidemiological aspects, fungicide resistance and the latest advancements in tools and technologies, aiming to guide future research and strategies to address the escalating threat to soybean crops globally. [ABSTRACT FROM AUTHOR]

Objective Head-neck paragangliomas (HNPGLs) are rare tumors with approximately half arising due to germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx). Patients with HNPGL have heterogeneous propensity to recur and metastasize. Thus, we aim to assess prevalence and predictors of recurrent (RD) and/or metastatic disease in patients with and without SDHx -related HNPGLs. Design and methods This cross-sectional study used retrospective data of 214 patients enrolled in six referral centers. Data included sex, age, primary tumor treatment, location, and size, biochemical phenotype, germline PVs, presence of RD (locoregional or new tumor), and/or metastasis. Results Patients with and without SDHx -related HNPGLs showed 74% and 40% prevalence of RD, respectively. Patients without SDHx -related HNPGLs presented with recurrent tumors only in head-neck regions. The only independent predictor for RD in the entire cohort was presence of SDHx PVs. Metastatic prevalence reached 9%-13%. For patients with SDHx -related HNPGLs, large tumor size (>2.3 cm, OR:50.0, CI:2.6-977.6), young age at initial diagnosis (<42years, OR:27.3, CI:1.8-407.2), and presence of SDHB PV (OR:15.6; CI:1.5-164.8) were independent predictors of metastasis. For patients without SDHx -related HNPGLs, only carotid-body location was an independent predictor of metastasis (OR:18.9, CI:2.0-182.5). Conclusions Patients without SDH x-related HNPGLs require long-term follow-up due to high prevalence of RD with imaging largely restricted to head-neck regions. As carotid-body HNPGLs have the highest metastatic risk among sporadic tumors, radical treatment with frequent follow-up is suggested until population-based data are available. Importantly, patients with SDHx -related HNPGLs might benefit from early radical treatment when tumors are still small to reduce metastatic risk. [ABSTRACT FROM AUTHOR]

Desmethylphosphinothricin (L-Glu-γ-PH) is the H-phosphinic analog of glutamate with carbon-phosphorus-hydrogen (C-P-H) bonds. In L-Glu-γ-PH the phosphinic group acts as a bioisostere of the glutamate g-carboxyl group allowing the molecule to be a substrate of Escherichia coli glutamate decarboxylase, a pyridoxal 50-phosphate-dependent α-decarboxylase. In addition, the L-Glu-γ-PH decarboxylation product, GABAPH, is further metabolized by bacterial GABA-transaminase, another pyridoxal 50-phosphate-dependent enzyme, and succinic semialdehyde dehydrogenase, a NADP+-dependent enzyme. The product of these consecutive reactions, the socalled GABA shunt, is succinate-PH, the H-phosphinic analog of succinate, a tricarboxylic acid cycle intermediate. Notably, L-Glu-γ-PH displays antibacterial activity in the same concentration range of well-established antibiotics in E. coli. The dipeptide L-Leu-Glu-γ-PH was shown to display an even higher efficacy, likely as a consequence of an improved penetration into the bacteria. Herein, to further understand the intracellular effects of L-Glu-γ-PH, 1H NMR-based metabolomics, and LC-MSbased shotgun proteomics were used. This study included also the keto-derivative of L-Glu-γ-PH, α-ketoglutarate-γ-PH (a-KGg-PH), which also exhibits antimicrobial activity. L-Glu-γ-PH and α-KG-γ-PH are found to similarly impact bacterial metabolism, although the overall effect of α-KG-γ-PH is more pervasive. Notably, α-KG-γ-PH is converted intracellularly into L-Glu-γ-PH, but the opposite was not found. In general, both molecules impact the pathways where aspartate, glutamate, and glutamine are used as precursors for the biosynthesis of related metabolites, activate the acid stress response, and deprive cells of nitrogen. This work highlights the multi-target drug potential of L-Glu-γ-PH and α-KG-γ-PH and paves the way for their exploitation as antimicrobials. [ABSTRACT FROM AUTHOR]

Bisphenol A, a traditional endocrine disruptor, has been implicated in male infertility. This study investigated the effect of Cucumeropsis mannii seed oil (CMSO) on bisphenol A (BPA)‐induced biochemical toxicity in the testicular mitochondria of male albino rats. The rats were assigned randomly to six experimental groups (n = 6), A, B, C, D, E, and F. Group A received 1 mL of olive oil. Groups B and C received 100 mL/kg body weight (BW) of BPA and 7.5 mL/kg BW CMSO, respectively. Rats in groups D, E, and F received preadministered doses of 100 mL/kg BW of BPA, 5 mL/kg BW of BPA, and 2.5 mL/kg BW of CMSO, respectively, followed by 6 weeks of exposure to those doses. Some mitochondrial enzymes, mitochondrial membrane potential (MMP), mitochondria testicular protein, and body weight of rats were determined using standard methods. BPA significantly reduced succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, NADH dehydrogenase, and monoamine oxidase activity. Also, BPA prominently decreased the MMP, mitochondrial testicular protein, and body weight of rats. Interestingly, coadministration of BPA and CMSO restored the dysregulated activities of the enzymes and levels of other biomarkers. We postulated that CMSO may be a promising drug for treating systemic toxicity caused by environmental toxicants such as BPA. [ABSTRACT FROM AUTHOR]

The increasing global reliance on pesticides for agricultural pest control has raised significant environmental concerns, particularly due to inadequate monitoring of emerging chemicals in surface waters. This study addresses the potential contamination of aquatic ecosystems by developing and validating a method for detecting trace amounts of four recently registered fungicides: three succinate dehydrogenase inhibitors (fluopyram, penthiopyrad, pydiflumetofen) and fluopicolide, a structurally related fungicide. Employing QuEChERS-based sample extraction combined with ultra-high-performance liquid chromatography (UHPLC-MS-MS), this method achieves detection limits of 0.1 to 0.2 μg/L, with recovery rates between 90% and 110%, and intra-day relative standard deviation values well within the acceptable range of less than 20%. Applied to surface grab water samples from the greater Melbourne area, Australia, the method successfully identified all four fungicides at trace levels, including a notable high concentration of fluopyram (7.3 μg/L) during autumn, with the others intermittently detected at lower concentrations. This study represents the first documented instance of quantifiable detections of these four fungicides in Australian surface water systems. Given their high toxicity to several organisms and the limited global data on these substances, our findings underscore the critical need for continuous monitoring to inform strategies to safeguard aquatic ecosystems from these chemicals. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, paragangliomas, and syringomyelia are uncommon diseases. Furthermore, in the absence of any genetic link and with less than five reported adult patients surviving unrepaired rare form of Tetralogy of Fallot, our case shows noteworthiness. The possibility of definitive treatment of these conditions is rendered unsafe due to this persistent defect. Thus, management and ongoing survival of this patient remains complex and challenging. [ABSTRACT FROM AUTHOR]

We aimed to investigate the relationship between superoxide dismutase 2‐related oxidative stress in the paraspinal muscles and spinal alignment, clinical skeletal muscle parameters, and mitochondrial function. Multifidus muscle samples from patients who underwent posterior lumbar surgery were analyzed. Patients with diseases affecting oxidative stress and spinal alignment were excluded. The superoxide dismutase 2 redox index was defined as the ratio of reactive oxygen species (superoxide) to antioxidant enzymes (superoxide dismutase 2) and was used as an index of oxidative stress. Patients were divided into two groups based on the superoxide dismutase 2 redox index. Spinal alignment, clinical skeletal muscle parameters, and succinic dehydrogenase (SDH) mean grayscale value were compared between the groups, with analyzes for both sexes. Multiple regression analyzes were used to adjust for the confounding effect of age on variables showing a significant difference between the two groups. Thirty‐five patients with lumbar degenerative diseases were included. No significant differences were observed between the two groups for any of the parameters in males; however, females with a higher superoxide dismutase 2 redox index had greater lumbar lordosis, lower grip strength, and higher SDH mean grayscale value than those with a lower index. Multiple regression analyzes revealed that the superoxide dismutase 2 redox index was an independent explanatory variable for lumbar lordosis, grip strength, and SDH mean grayscale value in female patients. In conclusion, superoxide dismutase 2‐related oxidative stress in the paraspinal muscles was associated with mitochondrial dysfunction and decreased grip strength in female lumbar degenerative disease patients. [ABSTRACT FROM AUTHOR]

Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families. [ABSTRACT FROM AUTHOR]

Altered mitochondrial structure and function are implicated in the functional decline of skeletal muscle. Numerous cytoskeletal proteins are known to affect mitochondrial homeostasis, but this complex network is still being unraveled. Here, we investigated mitochondrial alterations in mice lacking the cytoskeletal adapter protein, XIN (XIN-/-). XIN-/- and wild-type littermate male and female mice were fed a chow or high-fat diet (HFD; 60% kcal fat) for 8 weeks before analyses of their skeletal muscles were conducted. Immuno-electron microscopy (EM) and immunofluorescence staining revealed XIN in the mitochondria and peri-mitochondrial areas, as well as the myoplasm. Intermyofibrillar mitochondria in chow-fed XIN-/- mice were notably different from wild-type (large, and/or swollen in appearance). Succinate dehydrogenase and Cytochrome Oxidase IV staining indicated greater evidence of mitochondrial enzyme activity in XIN-/- mice. No difference in body mass gains or glucose handling was observed between cohorts with HFD. However, EM revealed significantly greater mitochondrial density with evident structural abnormalities (swelling, reduced cristae density) in XIN-/- mice. Absolute Complex I and II-supported respiration was not different between groups, but relative to mitochondrial density, was significantly lower in XIN-/-. These results provide the first evidence for a role of XIN in maintaining mitochondrial morphology and function. [ABSTRACT FROM AUTHOR]

ABSTRACT Succinate dehydrogenase inhibitor (SDHI) is an important fungicide to control grain diseases. For this reason, a series of novel pyrazole‐4‐carboxamide derivatives with an N‐methoxy group were designed and synthesized. All the target compounds were characterized by 1H NMR, 13C NMR, and HRMS. The compound 3c was further confirmed by X‐ray diffraction, which crystallized in the triclinic system, space group P‐1, Z = 2. The fungicidal activity results indicated that most of these compounds possessed good activity against Sclerotinia sclerotiorum at 50 ppm. Especially, compound 3h exhibited the best activity with the EC50 is 7.80 μg/mL, which is comparable with the positive control bixafen (EC50 = 6.70 μg/mL). Furthermore, the physicochemical properties, molecular docking simulation, ADMET analyses, DFT of compounds 3h, 3k and two commercial SDHIs, isoflucypram and pydiflumetofen, were investigated in this study. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. The back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA was recovered at 20 weeks. SDH staining was lower in CKD than in control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time. [ABSTRACT FROM AUTHOR]

Background: Mitochondria are considered the powerhouse of cells, and skeletal muscle cells are no exception. However, information regarding muscle mitochondria from different species is limited. Methods: Different muscles from cattle, pigs and chickens were analyzed for mitochondrial DNA (mtDNA), protein and oxygen consumption. Results: Bovine oxidative muscle mitochondria contain greater mtDNA (p < 0.05), protein (succinate dehydrogenase, SDHA, p < 0.01; citrate synthase, CS, p < 0.01; complex I, CI, p < 0.05), and oxygen consumption (p < 0.01) than their glycolytic counterpart. Likewise, porcine oxidative muscle contains greater mtDNA (p < 0.01), mitochondrial proteins (SDHA, p < 0.05; CS, p < 0.001; CI, p < 0.01) and oxidative phosphorylation capacity (OXPHOS, p < 0.05) in comparison to glycolytic muscle. However, avian oxidative skeletal muscle showed no differences in absolute mtDNA, SDHA, CI, complex II, lactate dehydrogenase, or glyceraldehyde 3 phosphate dehydrogenase compared to their glycolytic counterpart. Even so, avian mitochondria isolated from oxidative muscles had greater OXPHOS capacity (p < 0.05) than glycolytic muscle. Conclusions: These data show avian mitochondria function is independent of absolute mtDNA content and protein abundance, and argue that multiple levels of inquiry are warranted to determine the wholistic role of mitochondria in skeletal muscle. [ABSTRACT FROM AUTHOR]

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides play important roles in the control of plant fungal diseases. However, they are facing serious challenges from issues with resistance and cross‐resistance, primarily attributed to their frequent application and structural similarities. There is an urgent need to design and develop SDHI fungicides with novel structures. RESULTS: Aiming to discover novel potent SDHI fungicides, 31 innovative pyrazole β‐ketonitrile derivatives with diphenyl ether moiety were rationally designed and synthesized, which were guided by a 3D‐QSAR model from our previous study. The optimal target compound A23 exhibited not only outstanding in vitro inhibitory activities against Rhizoctonia solani with a half‐maximal effective concentration (EC50) value of 0.0398 μg mL−1 comparable to that for fluxapyroxad (EC50 = 0.0375 μg mL−1), but also a moderate protective efficacy in vivo against rice sheath blight. Porcine succinate dehydrogenase (SDH) enzymatic inhibitory assay revealed that A23 is a potent inhibitor of SDH, with a half‐maximal inhibitory concentration of 0.0425 μm. Docking study within R. solani SDH indicated that A23 effectively binds into the ubiquinone site mainly through hydrogen‐bonds, and cation–π and π–π interactions. CONCLUSION: The identified β‐ketonitrile compound A23 containing diphenyl ether moiety is a potent SDH inhibitor, which might be a good lead for novel fungicide research and optimization. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fusarium head blight (FHB) caused by Fusarium graminearum species complex (FGSG) remains a major challenge to cereal crops and resistance to key fungicides by the pathogen threatens control efficacy. Pydiflumetofen, a succinate dehydrogenase inhibitor, and phenamacril, a cyanoacrylate fungicide targeting myosin I, have been applied to combat this disease. Nonetheless, emergence of pydiflumetofen resistance in a subset of field isolates alongside laboratory‐induced facile generation of phenamacril‐resistant isolates signals a critical danger of resistance proliferation. RESULTS: Our study investigates the development of dual resistance to these fungicides in F. graminearum. Utilizing pydiflumetofen‐resistant (PyR) and ‐sensitive (PyS) isolates, we obtained dual‐resistant (PyRPhR) and phenamacril‐resistant (PySPhR) mutants on potato sucrose agar containing phenamacril. Mutation rates for phenamacril resistance were comparable between pydiflumetofen‐resistant and ‐sensitive isolates, implying independent pathways for resistance development. The mutants compromised in fungal growth, competitive viability and deoxynivalenol production, suggesting fitness penalties for the dual‐resistant mutants. However, no cross‐resistance was found with tebuconazole or fludioxonil. In addition, we characterized four critical amino acid changes (S217L, C423R, K537T, E420G) in the Myo1 that were verified to confer phenamacril resistance in F. graminearum. CONCLUSION: This research indicates the possibility of resistance development for both pydiflumetofen and phenamacril in F. graminearum and emphasizes the need for fungicide resistance management for FHB. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aquatic processing industry is increasingly aware of the need to ensure that slaughtering is carried out under high welfare standards, so there is a need to explore the impact of slaughter methods on fish fillets. This study aimed to investigate the effects of different slaughtering methods (M1, lethality by hammering; M2, gas mixture causing death; M3, lethality by clove oil anesthesia + ice slurry; M4, lethality by ice slurry; M5, lethality by gradient cooling) on the energy metabolism, apoptosis and flesh mass in grouper (Epinephelus fuscoguttatus). RESULTS: Therefore, 120 fish (24 per treatment) were slaughtered by the five methods. The results showed that the succinate dehydrogenase (SDH) enzyme activity of M5 sample was higher. The serum glucose level of M2 samples and DAPI staining fluorescence of M2 samples were the highest, indicating that the stress response of M2 was strong. In addition, the texture, pH, total volatile basic nitrogen (TVB‐N), thiobarbituric acid (TBA) and K value results showed M5 samples had better flesh quality. CONCLUSION: Gradient cooling lethality had the least effect on oxidative damage and apoptosis in grouper during cold storage as the gradient cooling lethality had the least effect on antioxidant enzyme activities. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1β and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats. [ABSTRACT FROM AUTHOR]

Abstract Background In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). Hypothesis/Objectives To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). Animals Ten healthy dogs, 21 dogs with PCC. Methods Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. Results Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%‐98%] vs 14% [11%‐26%]; P

Objective To investigate the impact of succinate dehydrogenase (SDH) on the modulation of human sperm functions. Methods The isolated human sperm were co-incubated with different concentrations (10, 20, 40 mmol/L) of SDH inhibitor disodium malonate for one or two hours. The activity of the SDH was measured by commercially available reagent kit, while the protein level of the SDH catalytic subunit SDHA was determined through Western blot analysis. Sperm functions were analyzed:1)The impact of disodium malonate on important motility parameters of un-capcitated sperm including progressive motility rate (PR), total motility (TM), average pathvelocity (VAP)and the ability of capacitated sperm to penetrate viscous media were be assessed using a computer aided semen analysis system. 2) Effect of disodium malonate on sperm survival rate was evaluated using the Eosin-Nigrosin microscopy. 3) The incidence of acrosome reaction in capacitated sperm was be detected by PSA-FITC staining assay following disodium malonate treatment. Results Disodium malonate had no effect on expression of SDH catalytic subunit SHDA protein in human sperm. However, it inhibited the catalytic activity of the SDH, sperm forward motility, total motility, and the ability of sperm to penetrate viscous media. These inhibitory effects were positively correlated with the concentration of disodium malonate. Furthermore, disodium malonate had no any influence on the occurrence of spontaneous acrosome reaction in capacitated sperm. Conclusions Disodium malonate impairs human sperm motility by inhibiting succinate dehydrogenase activity.

Background: The standardized extract ofmilk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)- induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms. Methods: A model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (ReactiveOxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides. Results: PM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II. Conclusion: Silibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II. [ABSTRACT FROM AUTHOR]

Background: Plant fungal diseases present a major challenge to global agricultural production. Despite extensive efforts to develop fungicides, particularly succinate dehydrogenase inhibitors (SDHIs), their effectiveness is often limited by poor retention of fungicide droplets on hydrophobic leaves. The off-target losses and unintended release cause fungal resistance and severe environmental pollution. Results: To update the structure of existing SDHIs and synchronously realize the efficient utilization, we have employed a sophisticated supramolecular strategy to optimize a structurally novel SDH inhibitor (AoH25), creating an innovative supramolecular SDH fungicide (AoH25@β-CD), driven by the host-guest recognition principle between AoH25 and β-cyclodextrin (β-CD). Intriguingly, AoH25@β-CD self-assembles into biocompatible supramolecular nanovesicles, which reinforce the droplet/foliage (liquid-solid) interface interaction and the effective wetting and retention on leaf surfaces, setting the foundation for enhancing fungicide utilization. Mechanistic studies revealed that AoH25@β-CD exhibited significantly higher inhibition of SDH (IC50 = 1.56 µM) compared to fluopyram (IC50 = 244.41 µM) and AoH25 alone (IC50 = 2.29 µM). Additionally, AoH25@β-CD increased the permeability of cell membranes in Botryosphaeria dothidea, facilitating better penetration of active ingredients into pathogenic cells. Further experimental outcomes confirmed that AoH25@β-CD was 88.5% effective against kiwifruit soft rot at a low-dose of 100 µg mL-1, outperforming commercial fungicides such as fluopyram (52.4%) and azoxystrobin (65.4%). Moreover, AoH25@β-CD showed broad-spectrum bioactivity against oilseed rape sclerotinia, achieving an efficacy of 87.2%, outstripping those of fluopyram (48.7%) and azoxystrobin (76.7%). Conclusion: This innovative approach addresses key challenges related to fungicide deposition and resistance, improving the bioavailability of agricultural chemicals. The findings highlight AoH25@β-CD as a novel supramolecular SDH inhibitor, demonstrating its potential as an efficient and sustainable solution for plant disease management. [ABSTRACT FROM AUTHOR]

Objective: 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [18F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque microenvironment. Here, we sought to address this gap by in situ mapping of the activity of selected major dehydrogenases involved in glucose metabolism in atherosclerotic plaques. Methods: In situ activity of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) was assessed in plaques from murine aortic root and brachiocephalic arteries and human carotid arteries. High-resolution 2-deoxy-D-[1,2-3H]glucose ([3H]2-deoxyglucose) autoradiography of murine brachiocephalic plaques was performed. Results: LDH activity was heterogeneous throughout the plaques with the highest activity in medial smooth muscle cells (SMCs). G6PD activity was mostly confined to the medial layer and to a lesser extent to SMCs along the fibrous cap. SDH and IDH activities were minimal in plaques. Plaque regions with increased [3H]2-deoxyglucose uptake were associated with a modestly higher LDH, but not G6PD, activity. Conclusions: Our study reveals a novel aspect of the metabolic heterogeneity of the atherosclerotic plaques, enhancing our understanding of the complex immunometabolic biology that underlies [18F]FDG uptake in atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: Coal represents a significant natural resource in our world, and its quality and commercial value is primarily determined by its heating capacity. Numerous scientists worldwide have attempted to explore the impact of various environmental factors on coal rank, yet their conclusions are often inconsistent. Methods: In this study, the Illumina MiSeq sequencing approach was used to analyze the bacterial community from a low-rank coal mine as well as a highrank mine. Moreover, we investigated the relationship between the physical and chemical properties of the coal and the bacterial composition. Results: Overall, we found that the high-rank coal exhibited higher heating value but higher total sulfur and lead levels. Considering the community of bacteria, the abundances of Phascolarctobacterium and Anaerostipes were highly elevated in the high-rank coal group. Most interestingly, the Anaerostipes abundance was correlated with coal quality positively. Additionally, the co-occurrence network of the bacterial community in the high-rank coal group showed much higher complexity. The bacterial functional potential predictions indicated elevated levels of phosphoenolpyruvate carboxykinase ATP, succinate dehydrogenase fumarate reductase flavoprotein subunit, and methylenetetrahydrofolate dehydrogenase NADP methenyltetrahydrofolate cyclohydrolase pathways. Conclusion: This study revealed that high-rank coal had more complicated cooccurrence network and elevated Anaerostipes abundance, which may suggest a potential biological pathway that can be explored to enhance coal quality. [ABSTRACT FROM AUTHOR]

Postharvest litchi is susceptible to browning that limits the development of litchi industry. Hydrogen sulfide (H2S) is an important bioactive molecule that can regulate many physiological processes. This study examined the effects of exogenous H2S on pericarp browning and related physiological mechanisms in postharvest litchi. The results exhibited that exogenous H2S treatment delayed the browning of litchi pericarp and reduced the damage to cell membrane integrity during storage. This treatment inhibited the energy losses of litchi fruit by increasing the activities of H+-ATPase, Ca2+- ATPase, cytochrome C oxidase (CCO) and succinate dehydrogenase (SDH) and regulating the expression of energy metabolism-related genes, including LcAtpB, LcSnRK2, LcAAC1, LcAOX1 and LcUCP1. In addition, H2S treatment increased the levels of fructose, glucose, sucrose, inositol, galactose and sorbose in litchi fruit, and promoted sucrose synthesis by regulating the activities of sucrose phosphate synthase (SPS), sucrose synthase (SS), acid invertase (AI) and neutral invertase (NI). Based on the current findings, we suggest that exogenous H2S enhances the energy supply and antioxidant activity of litchi by modulating energy and sugar metabolism, thereby inhibiting fruit browning and senescence. These results indicated that H2S treatment is an effective approach to maintaining the quality of litchi fruit and extending its shelf life. [ABSTRACT FROM AUTHOR]

Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B (SDHB) gene are susceptible to the development of PPGL. A physiologically relevant PCC patient-derived cell line hPheo1 was developed, and SDHB_KD cells carrying a stable short hairpin knockdown of SDHB were derived from it. An untargeted metabolomic approach uncovered an overactive polyamine pathway in the SDHB_KD cells that was subsequently fully validated in a large set of human SDHB-mutant PPGL tumor samples. We previously reported that treatment with the polyamine metabolism inhibitor N1,N11-diethylnorspermine (DENSPM) drastically inhibited growth of these PCC-derived cells in culture as well as in xenograft mouse models. Here we explored the mechanisms underlying DENSPM action in hPheo1 and SDHB_KD cells. Specifically, by performing an RNAseq analysis, we have identified gene expression changes associated with DENSPM treatment that broadly interfere with all aspects of lipid metabolism, including fatty acid (FA) synthesis, desaturation, and import/uptake. Furthermore, by performing an untargeted lipidomic liquid chromatography–mass spectrometry (LC/MS)-based analysis we uncovered specific groups of lipids that are dramatically reduced as a result of DENSPM treatment. Specifically, the bulk of plasmanyl ether lipid species that have been recently reported as the major determinants of cancer cell fate are notably decreased. In summary, this work suggests an intersection between active polyamine and lipid pathways in PCC cells. [ABSTRACT FROM AUTHOR]

This study investigated the effects of dietary resveratrol (RES) and β-Hydroxy-β-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups with thirty lambs per treatment: (1) H group (basal diet without RES or HMB); (2) H-RES group (1.5 g/day of RES); (3) H-HMB group (1250 mg/day of HMB); (4) H-RES-HMB group (1.5 g/day of RES and 1250 mg/day of HMB). The experiment was conducted for 100 days, including a pre-test period of 10 days and a formal period of 90 days. The results showed significantly increased concentrations of glutathione peroxidase, superoxide dismutase, and IgM in the H-RES-HMB group (p < 0.05), while the malondialdehyde levels were significantly decreased (p < 0.05). The glycolytic indices including creatinine kinase (CK), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) were significantly increased in the H-RES-HMB group compared with the others (p < 0.05). A histological analysis showed that the hepatic plate tissue in the H-RES-HMB group appeared normal with multiple cells. The transcriptomic analysis showed that the expression of genes associated with the calcium signaling pathway (MYLK2, CYSLTR2, ADCY1, HRH1, ATP2B2, NOS2, HRC, ITPR1, and CAMK2B) and the NF-κB signaling pathway (BCL2 and CARD14) in the H-RES-HMB group were upregulated. The key differential metabolites (d-pyroglutamic acid, DL-serine, DL-threonine, fumarate, and glyceric acid) were enriched in the pathways associated with D-amino acid metabolism, the citrate cycle (TCA cycle), and carbon metabolism. The combined transcriptomic and non-targeted metabolomic analyses showed the co-enrichment of differential genes (NOS2 and GLUD1) and metabolites (fumarate) in arginine biosynthesis-regulated glycolytic activity, whereas the differential genes (ME1, SCD5, FABP2, RXRG, and CPT1B) and metabolites (Leukotriene b4) co-enriched in the PPAR signaling pathway affected the immune response by regulating the PI3K/AKT and cGMP/PKG signaling. In conclusion, the dietary RES and HMB affected the hepatic antioxidant capacity, immune response, and glycolytic activity through modulating the transcriptome (BCL2, CAMK2B, ITPR1, and IL1R1) and metabolome (DL-serine, DL-threonine, fumaric acid, and glycolic acid). [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Aims: Lead exposure is known to induce oxidative stress and neurotoxicity. Nitric oxide (NO) plays an important role in modulating oxidative stress, with L-arginine as a precursor of NO and Nω-nitro-L-arginine (L-NNA) as an inhibitor of NO synthase, an enzyme that catalyses the production of nitric oxide (NO) from L-arginine. Methods: This study investigated the differential effects of L-arginine and L-NNA on markers of oxidative stress and biochemical changes in brain tissue from rats with different levels of resistance to hypoxia exposed to lead nitrate. Rats with either low or high resistance to hypoxia were exposed to lead nitrate (oral 3.6 mg lead nitrate/kg b.w. per day for 30 days) and treated with L-arginine (600 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate) or L-NNA (35 mg/kg b.w., i.p., 30 min before and after exposure to lead nitrate). Brain tissue samples were analysed for lipid peroxidation, oxidative modification of proteins, and activity of antioxidant enzymes, including superoxide dismutase, catalase, glutathione reductase, and peroxidase, and total antioxidant status (TAS). We also examined the biomarkers of biochemical pathways involving the activity of alanine and aspartate aminotransferases, succinate dehydrogenase (SDH), and α-ketoglutarate dehydrogenase (KGDH). In addition, the trend observed was supported by assessments of the acetylcholine levels and acetylcholinesterase activity (ACh-AChE system) in brain tissue. Results: In rats with low resistance to hypoxia, the L-arginine treatment significantly reduced lipid peroxidation and oxidative protein modification but increased antioxidant enzyme activity, suggesting a protective effect against lead-induced oxidative stress. Conversely, in rats with high resistance to hypoxia, L-NNA had a protective effect, reducing lead-induced oxidative damage and decreasing lipid peroxidation, whereas L-arginine exacerbated oxidative stress and impaired antioxidant defences. These findings were supported by corresponding changes in the acetylcholine-acetylcholinesterase system, reflecting the observed patterns of lead-induced oxidative stress and neurotoxicity. The study shows that L-arginine exerts a protective effect by reducing lead-induced oxidative damage via an improvement in TAS. Our study shows that lead nitrate exposure significantly increases ala-nine and aspartate aminotransferase activity in brain tissue, with L-arginine exacerbating and L-NNA reversing this effect. The lead nitrate exposure also affected the activities of SDH and KGDH, which are important for cellular energy production and hypoxia resistance, with L-arginine altering SDH activity depending on the level of resistance and L-NNA enhancing both SDH and KGDH activities. These trends were further validated by alterations in the AChAChE system, highlighting the differential role of NO-dependent mechanisms in modulating lead-induced neurotoxicity based on hypoxia resistance. Conclusions: These findings suggest potential targeted therapeutic strategies based on the oxidative stress profile and highlight the potential of nitric oxide system modulators in counteracting lead-induced biochemical alterations and the dynamics of the ACh-AChE system depending on the individual physiological reactivity of organisms. [ABSTRACT FROM AUTHOR]

Stimulation of mammalian cells with inflammatory inducers such as lipopolysaccharide (LPS) leads to alterations in activity of central cellular metabolic pathways. Interestingly, these metabolic changes seem to be important for subsequent release of pro‐inflammatory cytokines. This has become particularly clear for enzymes of tricarboxylic acid (TCA) cycle such as succinate dehydrogenase (SDH). LPS leads to inhibition of SDH activity and accumulation of succinate to enhance the LPS‐induced formation of IL‐1β. If enzymes involved in beta‐oxidation of fatty acids are important for sufficient responses to LPS is currently not clear. Using cells from various patients with inborn long‐chain fatty acid oxidation disorders (lcFAOD), we report that disease‐causing deleterious variants of Electron Transfer Flavoprotein Dehydrogenase (ETFDH) and of Very Long Chain Acyl‐CoA Dehydrogenase (ACADVL), both cause insufficient inflammatory responses to stimulation with LPS. The insufficiencies included reduced TLR4 expression levels, impaired TLR4 signaling, and reduced or absent induction of pro‐inflammatory cytokines such as IL‐6. The insufficient responses to LPS were reproduced in cells from healthy controls by targeted loss‐of‐function of either ETFDH or ACADVL, supporting that the deleterious ETFDH and ACADVL variants cause the attenuated responses to LPS. ETFDH and ACADVL encode two distinct enzymes both involved in fatty acid beta‐oxidation, and patients with these deficiencies cannot sufficiently metabolize long‐chain fatty acids. We report that genes important for beta‐oxidation of long‐chain fatty acids are also important for inflammatory responses to an acute immunogen trigger like LPS, which may have important implications for understanding infection and other metabolic stress induced disease pathology in lcFAODs. [ABSTRACT FROM AUTHOR]

In humans, loss of heterozygosity for defective alleles of any of the four subunits of mitochondrial tricarboxylic acid cycle enzyme succinate dehydrogenase (SDH, also Complex II of the electron transport chain) can lead to paraganglioma tumors in neuroendocrine cells. With the goal of developing mouse models of this rare disorder, we have developed various SDH conditional loss strategies. Based on recent lineage tracing studies, we hypothesized that conditional SDHC loss in early embryogenesis during migration of primordial neural crest cells that form the susceptible chromaffin cells of the adrenal medulla might induce paraganglioma. We triggered low levels of detectable SDHC loss in Sox10+ cells at E11.5 of mouse development. We report that, rather than developing adrenal medulla paraganglioma (pheochromocytoma), offspring survived with evidence of neural crest cell dysfunction. Phenotypes included mild lower extremity gait anomalies suggestive of neural tube closure defects and patches of unpigmented fur consistent with neural crest‐derived melanocyte dysfunction. These defects were not observed in mice lacking Sdhc knockout. Our results add to existing data suggesting that, unlike humans, even early embryonic (Sox10‐driven) SDHx loss is inadequate to trigger paraganglioma in mice of the genetic backgrounds that have been investigated. Instead, low levels of tricarboxylic acid cycle‐deficient neural crest cells cause mild developmental defects in hind limb and melanocyte function. This new model may be of interest for studies of metabolism during early neural crest cell development. [ABSTRACT FROM AUTHOR]

Fruit rots caused by filamentous fungi such as Monilinia fructicola and Monilinia laxa have a strong impact on crop yield and fruit commercialization, especially as they affect a wide variety of stone fruits. The antifungal efficacy of benzylidene-cycloalkanones has been previously described in in vitro assays against M. fructicola; so, this study aims to evaluate the in vivo inhibitory potential of these hybrids on fruits that have been inoculated with M. fructicola, and use molecular docking to visualize the main interactions of these molecules in the active site of the enzyme succinate dehydrogenase (SDH). The results indicate that compound C achieves the highest inhibition of both Monilinia species (15.7–31.4 µg/mL), spore germination in vitro (<10 µg/mL), and has promising results in vivo, without causing phytotoxicity in fruits. The results from molecular docking suggest that hydroxyl groups play a crucial role in enhancing the binding of compound C to SDH and contribute to the formation of hydrogen bonds with amino acid residues on the enzyme active site. [ABSTRACT FROM AUTHOR]

The bicuspid valve in sheep and goat showed similar anatomical features. The left atrio ventricular opening was circular and possessed valves. Both these species contained an anterior and a posterior leaflet. The anterior leaflet was large and semicircular with two zones while the posterior leaflet had three zones. The latter was divided into 2-3 scallops by clefts. The free edges of the cusps were attached to the papillary muscles by 6-9 chordae tendinae. Morphometric observations of these leaflets didn't show any significant variations in both species. The free-edge mean length, mean depth of these valves and the mean height of the aterio-posterior commissure and the posterior-anterior commissure were with insignificant differences. Histological features also revealed a similarity in both species. The leaflets were found attached to the annulus made of densely arranged collagen bundles. Lamina radialis formed the core of the leaflet and was composed of dense collagen fibers, few elastic and reticular fibers with fibrocytes and histiocytes. The atrial and ventricular surfaces were lined by a layer of endothelium. Beneath the endothelial lining was lamina spongiosa towards the atrial side and lamina fibrosa towards the ventricular side. The mean thickness of both these valves was with insignificant differences between these two species. These valves showed a mild to weak reaction to PAS in the lamina spongiosa, whereas a moderate activity for Alcian blue was observed in the endothelial linings that confirmed the presence of neutral and acid mucopolysaccharides. The reaction to acid and alkaline phosphatase activity was strong in fibrosa, moderate in spongiosa and weak in lamina radialis. The valves were negative for Oil red O and cholesterol activity. Moderately positive succinic dehydrogenase activity was observed at the endothelial surfaces of the leaflet in both species. [ABSTRACT FROM AUTHOR]

Background: In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). Hypothesis/Objectives: To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). Animals: Ten healthy dogs, 21 dogs with PCC. Methods: Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. Results: Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%‐98%] vs 14% [11%‐26%]; P <.001), and significantly lower tissue proportion of epinephrine (12% [1%‐62%] vs 86% [74%‐89%]; P <.001). Pheochromocytomas exhibited significantly lower fumarate (0.4‐fold; P <.001), and malate (0.5‐fold; P =.008) contents than NAs. Citrate was significantly higher in PCCs than in NAs (1.6‐fold; P =.015). One dog in the PCC group had an aberrant succinate : fumarate ratio that was 25‐fold higher than in the other PCCs, suggesting an SDHx mutation. Conclusions and Clinical Importance: This study reveals a distinct catecholamine content and TCA cycle metabolite profile in PCCs. Metabolite profiling might be used to uncover underlying pathogenic variants in TCA cycle genes in dogs. [ABSTRACT FROM AUTHOR]

Dental caries (DC) is one of the most common oral diseases and is mainly caused by Streptococcus mutans (S. mutans). The use of antibiotics against S. mutans usually has side effects, including developing resistance. N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC), a natural product, has great potential utility in antibacterial agents owing to its low toxicity and good biocompatibility. Thus, the purpose of the present study was to explore the antimicrobial activity of N-2-HACC against S. mutans through the permeability of the cell wall, integrity of cell membrane, protein and nucleic acid synthesis, respiratory metabolism, and biofilm formation. Our results confirmed that the MIC of N-2-HACC against S. mutans was 0.625 mg/mL with a 90.01 ± 1.54% inhibition rate. SEM observed the formation of cavities on the surface of S. mutans after 12 h N-2-HACC treatment. The level of alkaline phosphatase (AKP) activity was higher in the N-2-HACC treatment group than in the control group, indicating that N-2-HACC can improve the permeability of the cell wall. Also, N-2-HACC treatment can destroy the cell membrane of S. mutans by increasing conductivity and absorbance at 260 nm, decreasing cell metabolic activity, and enhancing the fluorescence at 488 nm. Respiratory metabolism revealed that the activities of the Na+-K+-ATP enzyme, pyruvate kinase (PK), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were decreased after N-2-HACC treatment, revealing that N-2-HACC can inhibit glycolysis and the tricarboxylic acid cycle (TCA cycle) of S. mutans. Moreover, N-2-HACC can also decrease the contents of the nucleic acid and solution protein of S. mutans, interfere with biofilm formation, and decrease the mRNA expression level of biofilm formation-related genes. Therefore, these results verify that N-2-HACC has strong antibacterial activity against S. mutans, acting via cell membrane integrity damage, increasing the permeability of cell walls, interfering with bacterial protein and nucleic acid synthesis, perturbing glycolysis and the TCA cycle, and inhibiting biofilm formation. It is suggested that N-2-HACC may represent a new potential synthetically modified antibacterial material against S. mutans. [ABSTRACT FROM AUTHOR]

Simple Summary: The precise structure and function of the intestinal tract, along with the underlying molecular mechanisms governing the production of translucent eggs, remain unclear. The present study revealed that translucent eggs exhibited a thicker eggshell and a lower egg yolk color, which may be attributed to a disruption in the plasma lipid metabolism of the laying hens, a reduction in their intestinal antioxidant capacity, a decline in digestive and absorptive processes, and an alteration in their metabolic capabilities. Furthermore, we identified a total of 471 differentially expressed genes (DEGs) in duodenal tissue from laying hens producing translucent and normal eggs, comprising 327 upwardly expressed genes and 144 downwardly expressed genes. Enrichment analysis revealed that the up-regulated genes were predominantly enriched in metabolism-associated pathways and oxidative phosphorylation pathways, offering novel insights for enhancing egg quality in commercial poultry production. Producing translucent eggs has been found to reduce the quality and safety of the eggs, as well as the demand from consumers. However, the intestinal function and the molecular mechanism for the production of translucent eggs remain uncertain. A total of 120 eggs from 276-day-old Jining Bairi were divided into two groups based on eggshell translucence: the translucent egg group (group T) and the normal group (group C). Group T exhibited thicker eggshells and a lower egg yolk color. Subsequently, we divided the chickens into translucent and normal groups based on their egg quality. We then assessed the plasma biochemical index, intestinal morphology and structure, enzyme activity, and antioxidant capacity of the hens producing translucent eggs compared to those producing normal eggs. The results showed that the ratio of duodenal villus length to crypt depth, succinate dehydrogenase (SDH) activity, chymotrypsin, total ATPase (T-ATPase), alkaline phosphatase (AKP), and glutathione peroxidase (GSH-Px) activities were decreased in the hens produced translucent eggs (p < 0.05), but malondialdehyde (MDA) content was increased (p < 0.05); jejunal lipase activity, Na+K+-ATPase activity, total antioxidant capacity (T-AOC), and GSH-Px activities were decreased (p < 0.05) in group T; ileal amylase and Ca2+Mg2+-ATPase activities were also decreased (p < 0.05) in group T. In addition, we identified a total of 471 differentially expressed genes (DEGs) in duodenal tissue, with 327 up-regulated genes and 144 down-regulated genes (|log2FC| ≥ 1 and p < 0.05). Enrichment analysis showed that the up-regulated genes, such as GSTT1, GSTO2, and GSTA3, were mostly enriched in metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, and oxidative phosphorylation pathways. The results of our study indicate that plasma lipid metabolism disorder, decreased intestinal antioxidant capacity, and altered intestinal metabolism capabilities may influence the formation of translucent eggs. [ABSTRACT FROM AUTHOR]

Atractylis flava Desf. (AF) is common plant that is widely used for its anti- inflammatory and antioxidant properties. The purpose of this study was, therefore, to evaluate the cytotoxic effect and the molecular basis of antioxidant and anti-inflammatory effects of the ethyl acetate extract (AFEAE) obtained from the whole plant A. flava. This was accomplished through the use of NR8383 alveolar rat macrophage cells. Cultures of alveolar rat macrophage cells were treated with AFEAE (25–800 μg/mL), and cell viability was determined via WST-1 and LDH tests. In turn, the gene expression levels of nuclear factor κB (NF-κB), tumor necrosis factor-alpha (TNFα), interleukin 1 beta (IL1-β), interleukin 6 (IL-6), mitochondrial dynamin like GTPase (OPA1), Succinate dehydrogenase complex subunit A (SDHA) and neutrophil cytosolic factor 1 (NCF1) were assessed by applying RT-qPCR. The results show that ethyl acetate extracts of A. flava have non-cytotoxic effects, and the gene expression analysis demonstrates that AFEAF extracts generate significant downregulation of NF-κB, TNFα, IL-1 β, IL-6, NCF1, OPA1 and SDHA, compared to untreated cells. This study reveals that Atractylis flava ethyl acetate extract administration may be considered as a potential therapeutic strategy for inflammatory related diseases. [ABSTRACT FROM AUTHOR]