Oxidative Energy Metabolism Research Articles

Allelopathy and underlying mechanism of mango (Mangifera indica) peel extracts on Alexandrium catenella

Harmful algal blooms (HABs) have always been a worldwide environmental issue. The methods based on the principle of allelopathy provide a novel direction for controlling HABs; however, there are a few studies on the application of allelopathic algaecides to control harmful algae in marine environments. Here we examined the algicidal capacity of 15 fruit peel extracts with biological activity on Alexandrium catenella. The results displayed that the mango peel extracts (MPE) showed efficient inhibition on species growth. The algicidal rate reached 93.32 ± 0.56% at 96 h after adding 5 g/L MPE to the culture medium of A. catenella. Furthermore, we found that the expression of key genes involved in PSII and PSI was downregulated as well as obstructed the electron transportation in the light reaction process and the synthesis of organic matter. The blocked photosynthetic chain induced the accumulation of substantial reactive oxygen species, resulting in severe peroxidation of the membrane lipids. Simultaneously, the expression pattern of key genes involved in the fatty acid, amino acid, and peroxisome breakdown pathways was upregulated, which suggested that the synthesis and decomposition of intracellular organic matter may be in an imbalanced state. The results above indicated that oxidative damage and energy metabolism disequilibrium are two key pathways by which MPE induced algal cell death. Furthermore, several kinds of active substances and their proportion in MPE had been identified by liquid chromatography quadrupole time-of-flight mass spectrometry. It is speculated that esters may be the important component playing an algicidal effect. However, the specific substance that plays a key role in inhibiting the growth of A. catenella and the algicidal mechanism remain to be further studied. This study might provide a new direction in the management of HABs in the future.

Effects of a β-glucan-enriched diet on biomarkers of oxidative stress, energy metabolism and lysosomal function in muscle tissue of European grayling (Thymallus thymallus L.)

Effects of a β-glucan-enriched diet on biomarkers of oxidative stress, energy metabolism and lysosomal function in muscle tissue of European grayling (<i>Thymallus thymallus</i> L.)

Anti-fatigue effect of pigeon meat hydrolysate on exercise mice and its underlying mechanism: Related to oxidative stress and energy metabolism

With the acceleration of the pace in modern society, fatigue caused by high-intensity physical work, long-term heavy mental work and lack of sleep has become a widespread and noticeable health problem. In this study, pigeon meat hydrolysate (PMH) with good antioxidant activity was prepared and the anti-fatigue effects of fractions in PMH with different molecular weights (MW) on exercise mice and the underlying mechanism were investigated. Results showed that mice gavaged with PMH and its fractions exhibited improved exhaustive swimming time when compared to the Control, with fraction at MW 1–5 kDa (PP2) showed the highest improvement. Meanwhile, PP2 decreased the levels of blood lactate acid (BLA) and blood urea nitrogen (BUN), and increased the contents of muscle and liver glycogen. And the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in myocyte of mice were significantly enhanced, with the outflow of creatine kinase (CK) reduced. PP2 also exhibited significant antioxidant activity by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reducing the production of malondialdehyde (MDA), especially at relative higher dosages (M-PP2 and H-PP2). Metabolomics study indicated that the differential metabolites between PP2 and the Control group in liver tissues of mice were mainly related to the energy metabolism and central nervous system regulation pathways. All these results demonstrated that PP2 fraction in PMH at a dosage higher than 0.5 mg/g of mice body weight could significantly enhance the exercise endurance of mice and exert excellent anti-fatigue ability via alleviating oxidative stress and modulating energy metabolism in mice.

Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress

Anhedonia induced by sustained stress exposure is a hallmark symptom of major depressive disorder (MDD) and in rodents, it can be accessed through the sucrose preference test (SPT). (R)-ketamine is a fast-acting antidepressant with less detrimental side effects and abuse liability compared to racemic ketamine. The present study combined high-throughput proteomics and network analysis to identify molecular mechanisms involved in chronic variable stress (CVS)-induced anhedonia and promising targets underlying (R)-ketamine rapid antidepressant response. Male Wistar rats were subjected to CVS for five weeks. Based on the SPT, animals were clustered into resilient or anhedonic-like (ANH) groups. ANH rats received a single dose of saline or (R)-ketamine (20 mg/kg, i.p.), which was proceeded by treatment response evaluation. After prefrontal cortex collection, proteomic analysis was performed to uncover the differentially expressed proteins (DEPs) related to both anhedonic-like behavior and pharmacological response. The behavioral assessment showed that the ANH animals had a significant decrease in SPT, and that (R)-ketamine responders showed a reversal of anhedonic-like behavior. On a molecular level, anhedonia-like behavior was associated with the downregulation of Neuronal Pentraxin Receptor (Nptxr) and Galectin−1 (Gal-1). These data reinforce a disruption in the inflammatory response, neurotransmitter receptor activity, and glutamatergic synapses in chronic stress-induced anhedonia. (R)-ketamine response-associated DEPs included novel potential targets involved in the modulation of oxidative stress, energetic metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length, converging to biological themes extensively documented in MDD physiopathology. Our data provide valuable insights into the molecular mechanisms underlying the response to (R)-ketamine and highlight these pathways as potential therapeutic targets for anhedonia. By addressing proteins involved in oxidative stress, energy metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length, we can target multiple key factors involved in the pathophysiology of MDD. Modulating these proteins could open avenues for novel therapeutic strategies and deepen our understanding of anhedonia, offering hope for improved outcomes in individuals facing this challenging condition. However, additional studies will be essential to validate these findings and further explore their therapeutic implications.

Multigenerational effects of combined exposure of triphenyltin and micro/nanoplastics on marine medaka (Oryzias melastigma): From molecular levels to behavioral response

In natural environments, micro/nanoplastics (MNP) inevitably coexist with various pollutants, making it essential to examine their combined toxicity and intergenerational effects on marine organisms. This study investigated the combined toxicity and intergenerational effects of exposure to triphenyltin (T), microplastics (M), nanoplastics (N), a combination of microplastics and triphenyltin (MT), and a combination of nanoplastics and triphenyltin (NT) on marine medaka. The results showed that all treatments had adverse and intergenerational effects on marine medaka. Regarding oxidative stress and energy metabolism, smaller sized plastic particles caused more significant damage to the organisms. However, MT inflicted greater gonadal system damage than NT, leading to imbalanced sex hormone levels. Additionally, T induced hyperactivity in fish, whereas MNP tended to induce behavioral depression. Notably, large plastic particles in the F0 generation had a more pronounced impact on depressive behaviors compared to smaller particles. These findings suggest that both individual and combined exposures to TPT and MNP can detrimentally affect marine medaka from the molecular to behavioral levels, posing risks to population sustainability. This study provided a robust theoretical foundation and deeper insights into the ecotoxicological impacts and risk assessments of coexisting pollutants.

Sterilization mechanism of CuCeOx on fungus: Oxidative damage and energy metabolism disequilibrium

Pathogens in bioaerosols and aquatic environment cause epidemic outbreak frequently. Relative to bacteria and virus, fungi has not received attention enough. The development of sterilization materials and mechanism on fungi are limited. In this study, we proposed a non-noble metal sterilization material CuCeOx in order to investigate its sterilization mechanism on target fungal Hanseniaspora uvarum collected from the air. The active components of CuCeOx were uniformly distributed and induced the production of R·. The reactive oxygen species (ROS) changed from R· to RO· upon contact with fungal cells. Transcriptomics identified 1665 Differentially Expressed Genes (DEGs), including 1540 up-regulated and 125 down-regulated genes. The cell wall and external encapsulation structure were firstly damaged when the fungus contacted with CuCeOx, and the related DEGs were significantly down-regulated. CuCeOx could exert great impact on the energy metabolism of the cell, especially on the process of oxidative phosphorylation, which contained 59 up-regulated and 2 down-regulated genes. The cell is not sufficient to cope with the adverse environment caused by oxidative stress and metal ion homeostatic imbalance, which then modulates the intrinsic apoptotic pathway triggering apoptosis.

Fecal microbiome analysis uncovers hidden stress effects of low stocking density on rainbow trout

BackgroundRecirculating aquaculture systems can cause chronic stress in fish when stocking density is too high. However, this study tested whether low stocking density can cause fish stress. Adult rainbow trout, with an average weight of 1.517 kg (± 0.39), were subjected to low (12 kg/m3 ± 0.94) and moderate (43 kg/m3 ± 2.03) stocking densities for 24 days in a recirculating system maintained at 15 °C. At the end of the experiment, fecal microbiome analysis was carried out using a 16S rRNA amplicon sequencing. Additionally, an untargeted plasma metabolomics analysis was conducted.ResultsThe moderate stocking density group harboured greater numbers of commensals, such as C. somerae, R. lituseburensis, and L. plantarum. In contrast, detrimental species such as S. putrifacens and P. putida were abundant in the low-stocking density fish. Functional microbiome profiling revealed vitamin B12 salvage and synthesis in moderate stocking densities, which may support intestinal tight junction function. Additionally, vitamin B1 biosynthesis pathways were more abundant in the moderate stocking density group, which may function towards oxidative energy metabolism and protect against oxidative stress. A complementary plasma metabolomics study, although done at slightly different stocking densities and duration, confirmed the presence of blood metabolic stress markers. Elevated levels of L-lactic acid and L-Norvaline, L-Valine, and L-glutamine, indicate low stocking density fish were under stress. Furthermore, a P4HA2 stress gene biomarker confirmed the occurrence of stress in low-density fish. This study suggests that low stocking density can induce stress in fish. Moreover, moderate stocking density leads to a distinct and beneficial fecal microbiome profile.ConclusionOur study highlights the potential benefits of optimizing the stocking density of fish in recirculating aquaculture systems. This can improve fish health and welfare, promoting a more resilient fecal microbiome.Graphical abstract

Investigation of the regulatory mechanisms of Guiqi Yimu Powder on dairy cow fatty liver cells using a multi-omics approach.

Fatty liver disease in dairy cows is a metabolic disorder that significantly affects their health and productivity, imposing a notable economic burden on the global dairy industry. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target features, has shown unique advantages in the prevention and treatment of various diseases. Guiqi Yimu Powder, a traditional TCM formula, enhances growth, boosts production efficiency, and strengthens immune function in livestock by regulating antioxidant along with anti-inflammatory pathways. However, its specific regulatory mechanisms on fatty liver in dairy cows remain unclear. This study aims to investigate the molecular-level effects and potential regulatory mechanisms of Guiqi Yimu Powder in a Trimethylamine N-oxide (TMAO) induced fatty liver cell model of dairy cows. We employed a comprehensive analysis integrating transcriptomics, proteomics, metabolomics, and network pharmacology. An in vitro dairy cow fatty liver cell model was established using TMAO to induce lipid accumulation. Cells were treated with the optimal TMAO concentration identified through preliminary experiments, and further divided into a lipid accumulation group and Guiqi Yimu Powder treatment groups. The treatment groups received varying concentrations of Guiqi Yimu Powder (10, 20, 30, 40, or 50 g/L). High-throughput omics sequencing technologies were utilized to perform a comprehensive analysis of the treated cells. Bioinformatics methods were applied to explore the regulatory effects, aiming to elucidate the specific impacts of Guiqi Yimu Powder on lipid metabolism, liver function, and related signaling pathways, thereby providing scientific evidence for its potential application in the prevention and treatment of fatty liver in dairy cows. Guiqi Yimu Powder treatment significantly affected 1,536 genes, 152 proteins, and 259 metabolites. KEGG enrichment analysis revealed that the significantly altered molecules are involved in multiple pathways related to the pathology of fatty liver, including metabolic pathways, glutathione metabolism, hepatitis B, and AMPK signaling pathway (p < 0.05). Notably, joint analysis highlighted the regulatory mechanisms of Guiqi Yimu Powder on glutathione cycling, with L-5-Oxoproline identified as an important metabolic compound. These findings indicate its impact on oxidative stress, energy metabolism, and liver function, suggesting potential therapeutic applications for fatty liver in dairy cows. This study elucidated the regulatory mechanisms of Guiqi Yimu Powder on fatty liver cells in dairy cows, providing new scientific evidence for its potential application in the prevention and treatment of fatty liver disease.

Potential mechanisms underlying podophyllotoxin-induced cardiotoxicity in male rats: toxicological evidence chain (TEC) concept.

Podophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant Dysosma versipellis (DV) which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with DV poisoning often experience adverse reactions when taking large doses in a short period. The heart is an important toxic target organ, so it is necessary to conduct 24-h acute cardiac toxicity studies on PPT to understand its underlying toxicity mechanism. Based on the concept of the toxicological evidence chain (TEC), we utilized targeted metabolomic and transcriptomic analyses to reveal the mechanism of the acute cardiotoxicity of PPT. The manifestation of toxicity in Sprague-Dawley rats, including changes in weight and behavior, served as Injury Phenotype Evidence (IPE). To determine Adverse Outcomes Evidence (AOE), the hearts of the rats were evaluated through histopathological examination and by measuring myocardial enzyme and cardiac injury markers levels. Additionally, transcriptome analysis, metabolome analysis, myocardial enzymes, and cardiac injury markers were integrated to obtain Toxic Event Evidence (TEE) using correlation analysis. The experiment showed significant epistaxis, hypokinesia, and hunched posture in PPT group rats within 24h after exposure to 120mg/kg PPT. It is found that PPT induced cardiac injury in rats within 24h, as evidenced by increased serum myocardial enzyme levels, elevated concentrations of cardiac injury biomarkers, and altered cardiac cell morphology, all indicating some degree of cardiac toxicity. Transcriptome analysis revealed that primary altered metabolic pathway was arachidonic acid metabolism after PPT exposure. Cyp2e1, Aldob were positively correlated with differential metabolites, while DHA showed positive correlation with differential genes Fmo2 and Timd2, as well as with heart injury markers BNP and Mb. This study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of PPT-induced acute cardiotoxicity, which involved oxidative stress, apoptosis, inflammatory response, and energy metabolism disorder.

Transcriptional dynamic changes in energy metabolism, protein synthesis and cell cycle regulation reveal the biological adaptation mechanisms of juvenile Acrossocheilus wenchowensis under acute temperature changes

In recent years, frequent acute temperature changes have posed a serious threat to the physiology and survival of fish. This study utilized RNA-Seq technology to analyze the transcriptional dynamics in the muscle tissues of Acrossocheilus wenchowensis under various acute temperature conditions (16◦C, 20◦C, 24◦C, 28◦C and 32◦C). Through comprehensive analysis, we identified 11509 differentially expressed genes (DEGs), a gene set (profiles 19) that was significantly up-regulated with increasing temperature, and two weighted gene co-expression network analysis (WGCNA) modules that were significantly correlated with acute temperature changes. Furthermore, we identified 28 transcription factors that are pivotal in oxidative stress and energy metabolism under acute temperature changes. Our results showed that, compared to the control group (24°C), KEGG functional enrichment analysis revealed significant enrichment of DEGs in the cell cycle, DNA replication, and p53 signaling pathway, with an overall trend of suppressed expression. This indicates that maintaining cell stability and reducing cell damage is an effective adaptive mechanism for A. wenchowensis to cope with acute temperature changes. Through STEM analysis and the black WGCNA module associated with high-temperature stress, we identified significant up-regulation of pathways and hub genes related to energy metabolism including oxidative phosphorylation, TCA cycle, purine metabolism, and glutathione metabolism, as well as the central roles of signal transduction pathways such as MAPK signaling pathway and AMPK signaling pathway, which synergistically regulate energy production. Under acute low-temperature stress, the turquoise WGCNA module highlighted significant up-regulation of hub genes associated with Ribosomal and Spliceosomal pathways related to protein synthesis and processing, as well as activation of calcium signaling pathways, which plays an important role in maintaining cellular function during low-temperature adaptation. These findings provide a critical theoretical and molecular basis for the adaptation of eurythermal fish to rapid temperature changes.

In vivo identification of bioactive components of Poria cocos for adjusting mitochondria against metabolic dysfunction-associated fatty liver disease

Currently, no specific treatment exists to alleviate metabolic dysfunction-associated fatty liver (MAFLD). Previously, Poria cocos (PC) effectively relieved MAFLD, but its bioactive components are still unknown. The bioactive substances in PC that regulate mitochondria function to alleviate MAFLD were thus determined. The L02 hepatocyte model induced by fat emulsion and the MAFLD rat model induced by a high-fat diet (HFD) were developed to explore the efficacy of PC against MAFLD. The activity of PC-derived components in the liver mitochondria of HFD-fed rats was evaluated using the L02 hepatocyte model. Additionally, the PC-derived components from the liver mitochondria were identified by ultra-high performance liquid chromatography/mass spectrometry. Finally, the anti-steatosis ability of PC-derived monomers and monomers groups was evaluated using the adipocyte model. PC maintained the mitochondrial ultrastructure, alleviated mitochondrial oxidative stress, and regulated the energy metabolism and the fatty acid β oxidation to relieve lipid emulsion-induced cellular steatosis and HFD-induced MAFLD. PC-derived components entering the liver mitochondria inhibited oxidative stress injury and improved the energy metabolism to fight cellular steatosis. Additionally, 15 chemicals were identified in the PC-treated rat liver mitochondria. These identified chemical molecules and molecule groups in the mitochondria prevented cellular steatosis by regulating mitochondrial oxidative stress and energy metabolism. PC restores mitochondrial structure and function, alleviating MAFLD, which is related to oxidative stress, energy metabolism, and fatty acid β oxidation. The identified 15 components may be the main effective PC components regulating mitochondria function to alleviate MAFLD. Thus, PC may be a promising mitochondrial regulator to prevent MAFLD.

APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons.

The apolipoprotein E4 (APOE4) allele represents the major genetic risk factor for Alzheimer's disease (AD). In contrast, APOE2 is known to lower the AD risk, while APOE3 is defined as risk neutral. APOE plays a prominent role in the bioenergetic homeostasis of the brain, and early-stage metabolic changes have been detected in the brains of AD patients. Although APOE is primarily expressed by astrocytes in the brain, neurons have also been shown as source for APOE. However, the distinct roles of the three APOE isoforms in neuronal energy homeostasis remain poorly understood. In this study, we generated pure human neurons (iN cells) from APOE-isogenic induced pluripotent stem cells (iPSCs), expressing either APOE2, APOE3, APOE4, or carrying an APOE knockout (KO) to investigate APOE isoform-specific effects on neuronal energy metabolism. We showed that endogenously produced APOE4 enhanced mitochondrial ATP production in APOE-isogenic iN cells but not in the corresponding iPS cell line. This effect neither correlated with the expression levels of mitochondrial fission or fusion proteins nor with the intracellular or secreted levels of APOE, which were similar for APOE2, APOE3, and APOE4 iN cells. ATP production and basal respiration in APOE-KO iN cells strongly differed from APOE4 and more closely resembled APOE2 and APOE3 iN cells, indicating a gain-of-function mechanism of APOE4 rather than a loss-of-function. Taken together, our findings in APOE isogenic iN cells reveal an APOE genotype-dependent and neuron-specific regulation of oxidative energy metabolism.

Metabolomics and Biochemical Benefits of Multivitamin and Multimineral Supplementation in Healthy Individuals: A Pilot Study.

Scientific evidence regarding the effectiveness of vitamin and mineral supplements in healthy individuals remains scarce. In a randomized, double-blind study, 30 healthy individuals were assigned to receive a single daily dose of multivitamin and multimineral supplementation or a double daily dose for 30 days. Before and after the intake, an untargeted metabolomics assay for serum metabolites was conducted by hydrophilic interaction liquid chromatography-mass spectrometry, and clinical assessments of peripheral blood samples were performed. A paired t-test for metabolic analysis, adjusted using the false discovery rate (FDR) and p-value correction method (rate of change > 2 and FDR < 0.05), the Shapiro-Wilk test, Student's t-test, and the Mann-Whitney U test were applied depending on the variable, with a 5% significance level. An impact on oxidative stress was observed, with a significant reduction in homocysteine levels and an increment of pyridoxic acid (vitamin B6). The effect on energy metabolism was shown by a significant increase in diverse metabolites, such as linoleoylcarnitine. Serum iron and calcium levels were also impacted. Overall, we observed a nutritional balance compatible with a good state of health. In conclusion, beneficial effects on adult health were demonstrated in relation to oxidative stress, energy metabolism, and nutritional balance.

Abamectin-induced behavioral alterations link to energy metabolism disorder and ferroptosis via oxidative stress in Chinese mitten crab, Eriocheir sinensis

The increasing application of abamectin (ABM) in agriculture has raised concerns regarding its environmental safety and potential adverse effects on aquatic environment safety. In the present study, the toxic effects of ABM exposure on the adult Chinese mitten crab, Eriocheir sinensis were investigated, with a focus on locomotion impairment, behavioral changes, oxidative stress, energy metabolism disruption, and ferroptosis. Crabs were exposed to sublethal concentrations of ABM at 2, 20 and 200 μg/L. After 21 d chronic exposure to 200 μg/L, residual ABM in hepatopancreas and muscles were detected as 12.24 ± 6.67 and 8.75 ± 5.42 μg/Kg, respectively. By using acute exposure experiments (96 h), we observed significant locomotion and behavioral alterations, alongside biochemical evidences of oxidative stress and energy metabolism impairment. The presence of ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, was notably identified in the hepatopancreas. Functional tests with N-acetylcysteine (NAC) supplementation showed restored behavioral responses and decrease of ferroptosis levels. It suggests that mitigating oxidative stress could counteract ABM-induced toxicity. Our findings highlight the critical roles of oxidative stress and ferroptosis in mediating the toxic effects of ABM on E. sinensis, underscoring the need for strategies to mitigate environmental exposure to pesticides.

The Effect Of L-Carnitine And Alpha Lipoic Acid Administration With Exercise In Old Rats On Energy Metabolism Related To Oxidative Stress Parameters

Objective: This study aims to contribute novel insights by investigating the potential positive effects of a combined dietary supplement and exercise program on mitochondrial oxidative stress and energy metabolism in aging. Focusing on the protective impact of Alpha Lipoic Acid (ALA), a potent antioxidant, against exercise-induced mitochondrial oxidative stress in rats, we also assess how L-Carnitine administration affects exercise ability by analyzing resistin and HbA1c levels, indicators linked to insulin resistance and cellular sensitivity. Methods: In this 10-day study, 42 old male Sprague Dawley rats (weighing 400±10 g, aged 15–17 weeks) were divided into six groups (n=7): Control, Exercise, L-Carnitine, Alpha Lipoic Acid (ALA), L-Carnitine+Exercise, ALA+Exercise. Relevant groups received daily oral gavage doses of L- Carnitine (50 mg/ml) and ALA (18 mg/ml). Exercise groups underwent treadmill sessions. On day 10, blood samples were quantitatively analyzed for HbA1c and Resistin levels using a Cusabio ELISA assay kit (China). Results: ALA supplementation synergistically reduced resistin and HbA1c levels, individually and combined with exercise. Conversely, L-Carnitine supplement, alone or with exercise, increased resistin levels but it caused a decrease in HbA1c levels. Conclusions: The data indicated a minor, insignificant decrease in resistin levels for the exercise and ALA groups, with a statistically significant difference in HbA1c levels among all groups. Exercise alone positively impacted both HbA1c and resistin levels, suggesting a potential counteraction of age-related oxidative stress and a positive influence on energy metabolism through an appropriate diet and exercise program. Further studies are required to explore specific metabolic pathways and relationships identified in our findings.

Multi-omics analysis of a case of congenital microtia reveals aldob and oxidative stress associated with microtia etiology.

Microtia is reported to be one of the most common congenital craniofacial malformations. Due to the complex etiology and the ethical barrier of embryonic study, the precise mechanisms of microtia remain unclear. Here we report a rare case of microtia with costal chondrodysplasia based on bioinformatics analysis and further verifications on other sporadic microtia patients. One hundred fourteen deleterious insert and deletion (InDel) and 646 deleterious SNPs were screened out by WES, candidate genes were ranked in descending order according to their relative impact with microtia. Label-free proteomic analysis showed that proteins significantly different between the groups were related with oxidative stress and energy metabolism. By real-time PCR and immunohistochemistry, we further verified the candidate genes between other sporadic microtia and normal ear chondrocytes, which showed threonine aspartase, cadherin-13, aldolase B and adiponectin were significantly upregulated in mRNA levels but were significantly lower in protein levels. ROS detection and mitochondrial membrane potential (∆ Ψ m) detection proved that oxidative stress exists in microtia chondrocytes. Our results not only spot new candidate genes by WES and label-free proteomics, but also speculate for the first time that metabolism and oxidative stress may disturb cartilage development and this might become therapeutic targets and potential biomarkers with clinical usefulness in the future.

Intravascular Laser Blood Irradiation (ILIB) Enhances Antioxidant Activity and Energy Metabolism in Aging Ovaries.

Ovarian aging is characterized by the accumulation of free radicals, leading to tissue damage and affecting reproductive health. Intravascular laser irradiation of blood (ILIB, using a low-energy He-Ne laser) is known for its efficacy in treating vascular-related diseases by reducing free radicals and inflammation. However, its impact on ovarian aging remains unexplored. This study aimed to investigate the effects of ILIB on oxidative stress and energy metabolism in aging ovaries. Genetic analysis was conducted on 75 infertile patients with aging ovaries, divided into ILIB-treated and control (CTRL) groups. Patients underwent two courses of laser treatment, and clinical parameters were evaluated. Cumulus cells were collected for the genetic analysis of oxeiptosis, glycolysis, and the tricarboxylic acid (TCA) cycle. The analysis of gene expression patterns revealed intriguing findings in ILIB-treated patients compared to the untreated group. Notably, ILIB treatment resulted in significant upregulation of oxeiptosis-related genes AIFM1 and NRF2, suggesting a potential protective effect against oxidative stress-induced cell death. Furthermore, ILIB treatment led to a downregulation of glycolysis-associated gene hexokinase 2 (HK2), indicating a shift away from anaerobic metabolism, along with an increase in PDHA levels, indicative of enhanced mitochondrial function. Consistent with these changes, ILIB-treated patients exhibited elevated expression of the key TCA cycle genes citrate synthase (CS), succinate dehydrogenase complex subunit A (SDHA), and fumarate hydratase (FH), signifying improved energy metabolism. The findings from this study underscore the potential of ILIB as a therapeutic strategy for mitigating ovarian aging. By targeting oxidative stress and enhancing energy metabolism, ILIB holds promise for preserving ovarian function and reproductive health in aging individuals. Further research is warranted to elucidate the underlying mechanisms and optimize the application of ILIB in clinical settings, with the ultimate goal of improving fertility outcomes in women experiencing age-related ovarian decline.

Litchi Pericarp Extract Treats Type 2 Diabetes Mellitus by Regulating Oxidative Stress, Inflammatory Response, and Energy Metabolism.

Litchi pericarp is rich in polyphenols, and demonstrates significant biological activity. This study assessed the therapeutic effects of litchi pericarp extract (LPE) on type 2 diabetes mellitus in db/db mice. The results showed that LPE ameliorated symptoms of glucose metabolism disorder, oxidative stress, inflammatory response, and insulin resistance in db/db mice. The mechanistic studies indicated that LPE activates adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and suppresses the protein expression of phosphoenolpyruvate carboxykinase (PEPCK), thereby reducing hepatic gluconeogenesis. Additionally, LPE facilitates the translocation of nuclear factor erythroid2-related factor 2 (Nrf2) into the cell nucleus, initiating the transcription of antioxidant factors superoxide dismutase (SOD) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which alleviate oxidative stress and reduce oxidative damage. Furthermore, LPE blocks nuclear factor kappa-B (NF-κB) nuclear translocation and subsequent inflammatory response initiation, thereby reducing inflammation. These findings indicate that LPE addresses type 2 diabetes mellitus by activating the AMPK energy metabolic pathway and regulating the Nrf2 oxidative stress and NF-κB inflammatory signaling pathways.

Ingredients in Rhus chinensis Mill. fruits oil relieve fatigue by reducing oxidative damage and regulating energy metabolism and gut microbiota

Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.

Multi-targets of antimicrobial photodynamic therapy mediated by erythrosine against Staphylococcus aureus identified by proteomic approach.

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus.