Glutathione

Abstract

Acute kidney injury (AKI) represents a significant complication in patients with COVID-19. Although Remdesivir (RDV) has been shown to reduce viral loads and improve clinical outcomes, concerns persist regarding its safety in individuals with pre-existing kidney impairment. This study investigated the effects of RDV on a rat model of ischemia/reperfusion (I/R)-induced kidney damage. A total of 24 rats were divided randomly into four groups: (1) control, (2) I/R, (3) I/R + RDV by intraperitoneal (ip) injections, and (4) I/R + RDV by subcutaneous (sc) injection groups. Rats in groups 3 and 4 received a single dosage of RDV (25 mg/kg) one hour before I/R induction. The effect of RDV on master genes involved in the mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator (PGC-1α)] and dynamics [Dynamin-related protein 1 (Drp-1)], cellular stress [Activating transcription factor 3 (ATF3)], inflammation [Nuclear factor kappa B (NF-κB)], cell death [p53, p21 (a cyclin-dependent kinase inhibitor), and caspase-3], as well as oxidant malondialdehyde (MDA) and antioxidant factors were evaluated. Moreover, renal function, along with histology assessments were studied. Significant reductions in mitochondrial biogenesis marker PGC-1α (P ≤ 0.04) and increases in caspase-3 (P = 0.003) expression levels were observed in the I/R + RDV + sc group compared to the I/R group. Oxidative stress marker was elevated (P = 0.016), while glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) were significantly decreased in the I/R + RDV + sc group (0.003 and 0.045, respectively). However, no significant changes were observed in p-p53, p-p21, NF-κB, or Drp-1 levels. Subcutaneous injection of RDV could induce more injury to the kidney compared to the intraperitoneal injection. These findings suggest that RDV may exacerbate AKI by hindering mitochondrial biogenesis and promoting renal cell apoptosis, without significantly affecting overall kidney function or histopathology. Clinically, these results highlight the need for caution when using RDV in patients with impaired renal function, especially during COVID-19 treatment.

Abstract

Caloric restriction (CR) stimulates taurine-conjugated bile acids (BA) synthesis in the liver. Upon secretion into the intestine, BAs undergo deconjugation, increasing taurine, and taurine conjugate levels, including taurine-glutathione (GSH). This study aimed to determine whether dietary taurine and CR-induced taurine changes operate through distinct regulatory mechanisms. Male C57Bl/6 mice were subjected to ad libitum feeding or 20% CR with low-taurine diet (LTD) or 5% taurine in drinking water. LTD and taurine supplementation minimally affected intestinal taurine concentrations and did not disrupt CR-induced changes in intestinal taurine levels, GSH conjugates, and GST expression, demonstrating mechanistic independence. Both interventions significantly altered hepatic and plasma taurine levels, indicating tissue-specific regulation. While CR primarily influenced GSH-S transferase (GST) mRNA expression in the intestine, GST activity correlated with substrate availability rather than gene expression. CR maintained enhanced intestinal taurine retention during taurine supplementation, evidenced by reduced fecal taurine excretion compared to controls. Dietary and CR-related taurine are affected by distinct tissue-specific mechanisms, with CR primarily impacting intestinal taurine while modulation of dietary taurine (restriction or supplementation) predominantly influences hepatic pools. The study reveals independent regulatory mechanisms governing taurine homeostasis and emphasizes differences between dietary factors and physiological responses during CR.

Abstract

Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100 μM, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100 μM. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs.

Abstract

Glutathione is a major component of the cellular antioxidant system, providing a means of controlling redox homeostasis and affording protection against oxidative damage. Proton magnetic resonance spectroscopy (MRS) offers insights into brain metabolism by enabling the noninvasive quantification of metabolites. Previous studies have demonstrated that the neurotransmitters glutamate and GABA detected by MRS show activity-dependent concentration changes and correlate with cognitive performance. Yet how MRS detected antioxidant capacity, particularly glutathione levels, relates to cognition remains unclear. In this issue, Lee et al. report that higher cortical glutathione levels are associated with better cognitive outcomes in older adults. These findings might contribute to understanding whether glutathione levels index resilience or degeneration. However, observations reported across the literature remain inconsistent, and the observed discrepancies underscore the need for further research using harmonized MRS acquisitions, deeper metabolic and cognitive phenotyping, and longitudinal study designs to clarify the role of cortical glutathione in cognitive trajectories.

Abstract

Glutathione (GSH), the most abundant cellular non-protein thiol and a central antioxidant, plays essential roles in regulating redox homeostasis, signal transduction, and detoxification processes. Altered GSH levels are closely associated with various pathological conditions, including neurodegenerative disorders, and liver injury. Notably, tumor tissues exhibit markedly elevated GSH concentrations (up to 4-10 times higher than in normal cells), where it promotes tumor proliferation, invasion, and chemoresistance by sustaining a reduced microenvironment, these characteristics make GSH an important biomarker and therapeutic target in oncology.

Abstract

Floccularia luteovirens mushroom polysaccharides (FLPs) have anti-inflammatory and antioxidant effects in many inflammatory diseases. However, its protective effect on alcoholic liver injury has not been studied. This study investigated the protective effects of FLPs on acute alcoholic liver injury in mice. After administering FLPs at doses of 200, 400, and 800 mg/kg for 14 days, it was found that FLPs could inhibit the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) in the serum. FLPs also significantly reduced the levels of four inflammatory factors, interleukin (IL)-1α, IL-1β, IL-33, and tumor necrosis factor-α (TNF-α) in the serum. All dose groups of FLPs could significantly inhibit the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in liver tissues. At the same time, they could significantly increase the levels of catalase (CAT) and glutathione peroxidase (GSH-Px), enhancing the antioxidant capacity of the body, which confirmed the protective therapeutic effects of FLPs against oxidative stress and inflammation in alcoholic liver injury. The Western blot assay investigated the effect of FLPs on the NF-κB/NLRP3 signaling pathway in the liver tissues of mice with alcoholic liver injury, indicating that its mechanism of action may be to inhibit the expression of inflammatory factors such as IL-1β and suppress the NF-κB/NLRP3 inflammasome signaling pathway to achieve antioxidant and anti-inflammatory effects.

Abstract

This study assessed the effects of 12-week green tea supplementation on fertility hormones and oxidative stress markers in obese males with varying gonadal statuses.

Abstract

The effects of foliar spraying different concentrations of glutathione （GSH）， cysteine （Cys）， and glutamic acid （Glu） on the phytoremediation by Solanum nigrum L. in heavy metal-contaminated soil were systematically investigated under the light conditions of 20% red light， 70% blue light， and 10% green light （R20B70G10）. The application of GSH， Cys， and Glu at various levels through foliar spraying yielded the following results： ① It promoted the growth of S. nigrum L. by increasing the dry weight of the plants by 15.0%-89.4%. Among them， the application of 2 mmol·L-1 GSH increased the dry weight of the plants by 82.0%. Furthermore， it enhanced the growth and elongation of the aboveground and underground parts of the plants， with plant height and root length exhibiting increases of 48.1% and 36.8%， respectively. ② It enhanced the photosynthetic efficiency of plants. The application of 2 mmol·L-1 GSH was shown to significantly enhance the actual photosynthetic efficiency [Y（Ⅱ）] and the photosynthetic electron transport rate （ETR） of photosystem Ⅱ in plants， with respective increases of 76.8% and 78.3% compared to those in the control group. ③ It enhanced the antioxidant capacity of S. nigrum L. The content of ascorbic acid （AsA） and GSH in the plant leaves increased by 22.7%-140.2% and 21.1%-80.6%， respectively. Among them， foliar spraying 2 mmol·L-1 GSH increased the AsA and GSH contents in the leaves by 126.4% and 57.1%， respectively. The activities of superoxide dismutase （SOD）， peroxidase （POD）， and catalase （CAT） in the plants increased by 137.5%， 312.3%， and 33.2%， respectively， and the activities of dehydroascorbate reductase （DHAR） and ascorbate peroxidase （APX） in the plants increased by 34.8% and 81.9%， respectively. The contents of malondialdehyde （MDA） and hydrogen peroxide （H2O2） in the plants decreased by 39.0% and 32.3%， respectively. ④ It also enhanced the activities of neutral phosphatase （NPH） and urease （URE） in the rhizosphere soil of S. nigrum L. The activities of NPH and URE in the soil increased by 11.4%-91.6% and 25.6%-111.4%， respectively. Among them， the activities of NPH and URE increased by 81.1% and 67.6%， respectively， when 2 mmol·L-1 GSH was applied through foliar spraying. ⑤ The effectiveness of S. nigrum L. in remediating heavy metal-contaminated soil was strengthened. Foliar spraying of GSH and Cys could significantly increase the accumulation of cadmium （Cd） in S. nigrum L. Among them， the application of 2 mmol·L-1 GSH significantly improved the accumulation and translocation capacity of S. nigrum L. for Cd. Specifically， its translocation factor （TF）， bioconcentration factor （BCF）， and total extraction （TE） increased by 97.2%， 148.7%， and 209.4%， respectively， and the maximum value of TE could reach 0.132 mg·plant-1. Thus， foliar spraying of 2 mmol·L-1 GSH， Cys， and Glu can significantly increase the biomass of S. nigrum L. under heavy metal stress. It enhances the antioxidant capacity and reduces oxidative damage， promotes the plant to absorb and accumulates heavy metals， and strengthens the phytoremediation effect. Overall， the treatment of foliar spraying 2 mmol·L-1 GSH had the best effect.

Abstract

Nitric oxide (NO) inhibits climacteric fruit ripening, but its mechanisms remain elusive. Here, S-nitrosoglutathione (GSNO, a NO donor) reduces carotenoid accumulation in tomato fruit, confirming NO's role as carotenoid biosynthesis suppressor. Transcriptome analysis identified SlSPL10 (SQUAMOSA promoter binding protein-like 10) as a key player during this process. Genetic evidence further revealed that SlSPL10 negatively regulates carotenoid synthesis. Moreover, GSNO fails to suppress carotenoid synthesis in slspl10 mutant fruit, in contrast to wild-type fruit, highlighting the involvement of SlSPL10 in NO-inhibited carotenoid synthesis. Transcriptomic profiling of slspl10 mutant fruit showed that both NO and SlSPL10 regulate key carotenoid synthesis genes (SlGPS, SlPDS, SlZDS, SlZISO, and SlCRTISO). SlSPL10 directly binds to the promoters of these genes to repress their transcription, and NO enhances the transcriptional inhibition of SlGPS, SlZISO, and SlCRTISO. These three genes are indispensable for SlSPL10's role in NO-mediated carotenoid suppression. Collectively, NO enhances SlSPL10-mediated repression of carotenoid biosynthesis gene expression, reducing carotenoid accumulation in tomato fruit.

Abstract

Biotin is a vital coenzyme involved in diverse metabolic pathways and plays a key role in hoof health by supporting keratin synthesis and the protective barrier of the hoof. This study systematically investigated the effects of rumen-protected biotin (RPB) on hepatic metabolic networks, redox homeostasis, and hoof health in lactating dairy cows using an integrated multiomics approach. The RPB supplement consisted of 2.1% biotin (purity ≥99%), 62.9% glucose, and 35% hydrogenated palm oil fatty acids. Eighty multiparous Holstein cows were stratified by parity (2.48 ± 0.69), body weight (637.76 ± 55.71 kg), body condition score (3.01 ± 0.20), days in milk (141 ± 16), and average milk yield (32.35 ± 4.36 kg/d). They were assigned for 75-d using a randomized block design to 4 treatment groups: Control (Con; basal diet, n = 20), Low (0.5 g/d RPB, n = 20), Mid (1.0 g/d RPB, n = 20), or High RPB (2.0 g/d RPB, n = 20). Milk and blood samples were collected on d 0, 15, 30, 45, 60, and 75 for analysis of milk composition and serum biochemical parameters. Data were analyzed using mixed models with orthogonal polynomial contrasts to evaluate linear and quadratic effects of RPB. Among the markers of liver function, serum albumin increased but total cholesterol, alanine aminotransferase, aspartate aminotransferase, and total bilirubin decreased in a linear and quadratic fashion with higher doses of RPB. Feeding RPB increased serum total antioxidant capacity, glutathione, and superoxide dismutase in a linear and quadratic fashion, while malondialdehyde decreased. Incremental feeding of RPB decreased linearly the serum type II collagen C-terminal peptide concentration and lameness scores. Further, serum cartilage oligomeric matrix protein concentration decreased in a linear and quadratic fashion, whereas serum procollagen IIA N-terminal propeptide and hoof horn hardness increased in a linear and quadratic fashion. Based on serum biochemical and hoof health results on d 75, the Con and Mid groups were selected for proteomic and metabolomic analyses of serum. Proteomics revealed that RPB upregulated key proteins involved in antioxidant reactions and keratinization, including GSR, GCLC, GPX3, TGM1, and TGM3. Metabolomics identified L-cysteine, glycine, and pyruvate as key metabolites associated with RPB suggesting upregulated glutathione synthesis and flux through the tricarboxylic acid cycle. Integrated proteomics and metabolomics analyses revealed that GSR, GCLC, GPX3, TGM1, and TGM3 were positively correlated with L-cysteine and glycine but negatively correlated with γ-glutamylcysteine and palmitic acid. Overall, feeding RPB reduces oxidative stress and improves liver function in part by enhancing glutathione metabolism while reducing lipid peroxidation. Further, RPB promotes keratinization and limits cartilage degradation, thereby enhancing hoof health. These responses to dietary RPB supplementation provide molecular evidence for its targeted application in dairy herd nutrition management.

Abstract

Small molecule glucagon-like peptide-1 receptor (GLP-1R) agonists are pursued intensively in the pharmaceutical industry considering their advantages in outstanding patient adherence, cost and productivity relative to injectable ones. A series of novel small molecules had been made by rationale design with computer aided drug design (CADD) assistance and evaluated in in vitro and in vivo druggability profilings. Among them, compound 6 with unique binding mode with GLP-1R showed robust efficacy in accumulation of cyclic adenosine monophosphate (cAMP) production cell assay. Compound 6 showed good metabolic stability in both human microsomes and hepatocytes and good to excellent drug exposure and bioavailability in four preclinical species in absorption, distribution, metabolism, excretion (ADME) and pharmacokinetics (PK) studies. It had no human ether-à-go-go-related gene (hERG) potassium channel inhibition liability and no time-dependent inhibition (TDI) and cytochrome P450 (CYP450) induction potential in in vitro tests as well. It also exhibited high plasma stability with no glutathione (GSH) trapping risk. In an intraperitoneal glucose tolerance test (IPGTT) study conducted in humanized-GLP-1R mice, compound 6 displayed impressive blood glucose lowering effect. These preclinical characteristics of compound 6 position it as a promising oral anti-diabetes and anti-obesity candidate that differentiate mainstay injectable peptide drugs.

Abstract

The development of non-invasive diagnostic tools for Parkinson's disease (PD) remains an unmet clinical need. Given the contribution by peripheral metabolism and environmental factors toward PD pathogenesis, comprehensive profiling of the plasma phenome could enable early disease detection. Accordingly, this study aimed to develop a non-invasive diagnostic panel for PD, to comprehensively characterize potential environmental triggers of PD pathogenesis, and to delineate the relationship between peripheral metabolism and disease progression.

Abstract

The present study focused on evaluating serum cytokines in SCD cases and understanding these mediators' interplay with immune cells and their impact on disease severity score(DSscore).

Abstract

Increased use of oral contraceptives and implants has necessitated the need to examine biochemical changes associated with their use.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress-induced liver injury that is closely related to type 2 diabetes mellitus (T2DM). Ursolic acid (UA), a natural pentacyclic triterpenoid compound, has anti-inflammatory, hypoglycemic and liver-protective effects. However, its role in regulating liver injury through the NLRP3 inflammasome pathway in a T2DM combined with NAFLD model has not been systematically elucidated. This study systematically evaluated the protective effect of UA on NAFLD and its molecular mechanism through in vivo (STZ + high-fat diet-induced NAFLD mouse model) and in vitro (high glucose + palmitic acid-induced LO2 cell oxidative stress model) experiments. The results showed that UA significantly improved hepatic lipid deposition, reduced serum ALT/AST levels, and effectively alleviated oxidative stress, as indicated by decreased malondialdehyde (MDA) content and increased activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in liver tissues. Further mechanism studies revealed that UA could significantly down-regulate the expression levels of pro-inflammatory factor IL-1β and pro-fibrotic factor TGF-β1 by inhibiting NLRP3 inflammasome activation, and simultaneously reduce the deposition of type IV collagen. This study demonstrated that ursolic acid (UA) has a protective effect on T2DM combined with NAFLD, and its mechanism of action may be related to the regulation of the NLRP3 signaling pathway by UA, which inhibits oxidative stress, inflammation and fibrosis.

Abstract

5-Fluorouracil (5-FU) is a chemotherapeutic agent used primarily to treat various cancers. While it has been successful in improving cancer survival rates, 5-FU is also known to be cardiotoxic. Treatment options for patients experiencing 5-FU-induced cardiotoxicity are limited to standard heart failure medications.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, synovial hyperplasia, and systemic complications. Current treatment options have side effects and limitations, leading to a growing interest in alternative therapies.

Abstract

Polysorbate 80 (PS80) is a commonly used surfactant for stabilizing biotherapeutics by preventing protein adsorption at the air-liquid interface. However, PS80 is susceptible to oxidative degradation during manufacturing and storage. We show here that light exposure combined with the presence of metals can result in byproduct formation and potentially decrease the surfactant's ability to prevent protein adsorption to the air-liquid interface. PS80 formulated in citrate buffer can undergo cis/trans isomerization of unsaturated fatty acids in the presence of disulfides and iron (Prajapati et al., 2022). This work investigates novel surface activity aspects of polysorbate formulations before and after exposure to UV-A light. Polysorbate samples of different grades were formulated in citrate buffer containing iron and glutathione disulfide (GSSG; as a surrogate for peptide and protein disulfides), and a Langmuir trough was used to monitor the surface pressure during adsorption to the air-solution interface. Our results showed significant changes in the polysorbate surface activity after photoirradiation: all-oleate PS80 exhibited a 3-fold increase in the apparent critical micelle concentration (CMC), and the presence of both cis and trans fatty acids was confirmed. Also, the impact of photoirradiation on surface pressure depended on the surfactant concentration during irradiation, suggesting that the presence of micelles can alter the degradation pathway and byproduct formation.

Abstract

Digestibility is a key determinant of the nutritional quality of food proteins, while disulfide bonds (SSs) restrict enzymatic hydrolysis. This study isolated and characterized endogenous small thiol compounds (ESTCs) from defatted soy meal and investigated their effects on SS cleavage and soy proteins' in vitro digestibility. The results revealed ESTCs are a <500 Da complex mixture of glutathione, cysteine-cysteine dipeptides, and cysteine-rich peptides. ESTC-induced SS cleavage was profoundly influenced by protein predenaturation, temperature, and pH, while excessive heat or high pH treatments impaired SS cleavage, but urea denaturation enabled the highest degree of SS cleavage (DSC) of 44.5%. Reaction kinetics revealed activation energies of 35.3 and 13.6 kJ/mol for undenatured and urea-denatured proteins, respectively. Compared to samples with 0% DSC, SS-cleaved proteins with DSCs of 7.2%, 22.1%, and 44.5% showed significantly increased hydrolysis degrees. This study proposed a green strategy through molecular modification to improve the nutritional quality of soy proteins.

Abstract

Acyl glucuronides (AG), reactive metabolites formed via the glucuronidation of carboxylic acid-containing drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), are closely associated with drug-induced liver injury (DILI), particularly idiosyncratic types. AG can covalently bind to proteins, potentially disrupting their function and triggering immune responses. Their toxicity is influenced by chemical instability, stereoselectivity, and interactions with specific uridine 5'-diphospho-glucuronosyltransferase (UGT) isoforms. Transporters such as multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) mediate AG disposition, while enzymes like β-glucuronidase and esterases regulate AG degradation. Studies have shown that AG derived from NSAIDs differ in their ability to form protein adducts, with propionic acid derivatives exhibiting higher reactivity. Glutathione (GSH), a key detoxifying molecule, plays a critical role in mitigating AG toxicity. GSH depletion in rats has been shown to increase AG accumulation and protein binding, even for drugs generally considered safe. Quantitative analysis of AG formation, degradation, and protein binding using liver microsomes and LC-MS/MS has revealed that AG degradation rates can distinguish between safe drugs, those requiring a warning, and those withdrawn. Furthermore, AG exhibit stereoselective binding to UGTs, with R-enantiomers often showing higher reactivity. These findings underscore the importance of evaluating AG kinetics and protein interactions in predicting DILI risk. Future research should focus on the qualitative assessment of AG-protein adducts and the development of personalized risk models. Integrating AG behavior into drug safety evaluations may enhance the prediction and prevention of DILI, contributing to safer drug development and regulatory strategies.

Abstract

The pathogenesis of epilepsy is closely associated with ferroptosis in hippocampal neurons. The Keap1-Nrf2-HO-1/GPX4 signaling pathway serves as a crucial endogenous antioxidant system and plays a significant role in regulating cellular ferroptosis. Caogouzhimu decoction has demonstrated potential antiepileptic effects in clinical practice, yet whether it intervenes in neuronal ferroptosis via this signaling pathway remains unclear.

Abstract

This study investigated the effects of ageing period (5 vs. 90 days) and meat status (raw vs. cooked) in a 2 × 2 factorial design on the concentration of bioactive compounds, intramuscular fat content and fatty acid composition of the longissimus lumborum muscle in beef. Samples were collected from 20 Angus steers finished on pasture. Significant (P < 0.05) interactions between ageing period and meat status were found for l-carnitine, glutathione, and taurine. Taurine and glutathione concentrations were greater (P < 0.05) in raw beef aged for 90 days, while L- carnitine content was lower in cooked meat aged for 5 days than the other treatments. Concentrations of coenzyme Q10, glutathione, l-carnitine, and taurine were higher (P < 0.05), and carnosine and anserine content were lower (P < 0.05) in meat aged for 90 days compared to 5 days. All bioactive compounds presented greater (P < 0.05) concentrations in raw than cooked meat. Beef aged for 90 days presented a greater (P < 0.05) proportion of intramuscular fat (IMF), and concentrations of saturated fatty acids (SFA), monounsaturated (MUFA), n-6 polyunsaturated fatty acids (PUFA)/n-3 PUFA ratio, atherogenic and thrombogenic indices. Cooking increased (P < 0.05) the concentrations of all fatty acids, however the PUFA/SFA ratio was greater (P < 0.05) in raw meat. Our findings show that ageing and cooking affect the bioactive compounds concentrations and fatty acids present in beef, and both factors should be considered to really know what meat provides under the conditions in which it is consumed.

Abstract

In our previous study, tripterygium glycosides (TG) demonstrated to combine with cisplatin (DDP) in reversing DDP resistance in A2780/DDP cells by exacerbating ferroptosis via downregulation of glutathione peroxidase 4 (GPX4) and cystine/glutamate antiporter (System Xc-) expression. However, the regulation of ferroptosis-related proteins alone is insufficient to explain the reversal of DDP resistance in epithelial ovarian cancer (EOC), suggesting the involvement of additional mechanisms.

Abstract

WLJCP-A-b (29.8 kDa), a novel water-soluble pectin, was extracted from Lonicerae Japonicae Caulis and subsequently purified using DEAE-Cellulose and Sepharose CL-6B columns. FT-IR and FT-Raman spectra combined with NMR spectroscopy indicate that WLJCP-A-b is a low methyl-esterified homogalacturonan (HG) type pectin covalently linked with RG-II and minor RG-I domains, with a degree of methyl-esterification of 29.5 %. Oligogalacturonides produced from HG domain were non-, mono-, di-, tri-, or tetra-esterified and/or acetyl-esterified with a 1 to 8 degree of polymerization. In vitro experiments showed that WLJCP-A-b possessed stronger antioxidant activity and protected INS-1 cells against tert-butyl hydroperoxide (TBHP)-induced oxidative damage by improving cell survival and insulin secretion, as well as maintaining mitochondrial function in β-cells, in part this might due to the presence of high galacturonic acid (GalA) and low methyl-esterified degree. Notably, WLJCP-A-b was found to effectively promote the expression levels of glutaredoxin 2 (Grx2) and glutathione reductase (GR), improve the GSH/GSSG ratio and the NADPH/NADP+ ratio, and enhance the activities of antioxidant enzymes, including glutathione peroxidase (GPx) and glutathione S-transferase (GST). These findings provided novel insights into the structure-activity relationship and molecular mechanisms of the antioxidant and protective effects of pectin from Lonicerae Japonicae Caulis on TBHP-induced INS-1 cells.

Abstract

Microplastics (MPs) are known to induce diverse toxic effects across biological systems; however, how environmentally photoaged MPs influence organismal aging and the underlying mechanisms remain poorly understood. Here, virgin polystyrene (PS-0) and 45-day photoaged polystyrene (PS-45) were evaluated at environmentally relevant concentrations (0-100 μg/L) to assess aging-related effects and molecular pathways in Caenorhabditis elegans. Photoaging markedly altered PS physicochemical properties, including surface morphology, crystallinity, and functional groups. Exposure to 100 μg/L PS-0 or PS-45 significantly shortened lifespan, impaired physiological behaviors, and increased lipofuscin accumulation, whereas PS-45 at 10-100 μg/L elicited substantially stronger pro-aging effects. These enhanced toxicities were driven by particle-associated processes, particularly elevated environmentally persistent free radical generation and increased particle accumulation in nematodes. Mechanistically, PS-45 inhibited DAF-16 nuclear translocation and dysregulated insulin/IGF-1 signaling genes (daf-2, age-1, pdk-1, akt-1, and daf-16). Concurrently, PS-45 induced ferroptosis, as evidenced by increased Fe2+ and malondialdehyde levels, glutathione depletion, and suppression of ftn-1; these effects were alleviated by the ferroptosis inhibitor ferrostatin-1. Mutations in daf-2, age-1, pdk-1, akt-1, daf-16, and ftn-1 significantly altered PS-45-induced aging phenotypes and ferroptotic stress, identifying the DAF-2-AGE-1-PDK-1-AKT-DAF-16-FTN-1 axis as a central regulatory pathway. Collectively, this study reveals a mechanistic link between insulin signaling and ferroptosis in MPs-induced aging and highlights the elevated environmental health risks posed by photoaged MPs.

Abstract

Sepsis-associated lung injury (SALI) remains a critical clinical challenge, partly driven by ferroptosis-induced endothelial dysfunction. The pathological interaction between FUN14 domain-containing protein 1 (FUNDC1) and glutathione peroxidase 4 (GPX4) promotes ferroptosis and disrupts mitophagic flux. Magnesium lithospermate B (MLB), an active compound derived from Salvia miltiorrhiza, possesses anti-inflammatory and antioxidant properties and exhibits potential for vascular protection. Here, it is demonstrated that MLB mitigates sepsis-associated pulmonary vascular injury by suppressing ferroptosis and restoring mitochondrial homeostasis. Mechanistically, MLB directly binds GPX4 at Gly79, thereby disrupting the GPX4-FUNDC1 interaction, stabilizing GPX4 enzymatic activity, and preventing its FUNDC1-mediated mitophagic degradation. To enhance pulmonary targeting, P-selectin-binding peptide-engineered adipose-derived stem cell extracellular vesicles were constructed to deliver MLB, substantially improving its therapeutic efficacy in SALI. Furthermore, a silver-citrate nanostructure-based surface-enhanced Raman spectroscopy platform was developed, enabling precise identification of MLB's Raman fingerprint spectrum with nanogram-level sensitivity and time-resolved in vivo biodistribution profiling. Collectively, these findings reveal a novel therapeutic mechanism and efficacy of MLB in SALI, highlighting a promising translational strategy that integrates targeted drug delivery with molecular detection for potential clinical applications.

Abstract

Benzothiazoles (BTZ) possess various medicinal benefits and in this study, we have synthesized benzothiazole derivatives by substituting its side chains, and analyzed its spectral analysis along with its antioxidant and anti-inflammatory activity. In-vitro antioxidant activity of the benzothiazole derivatives indicated strong antioxidant potential of 3b, 3d and 3e which were then evaluated for their anti-inflammatory potential in mice's paw edema and ethanol-induced gastric ulcer (GU). The compounds demonstrated strong anti-inflammatory ability in paw edema as well as ethanol-induced gastric ulcer. This was further confirmed by H&E staining and suppressed inflammatory mediators as tumor necrotic factor (TNF-α), nuclear factor B (p-NFkB), and cyclooxygenase-2 (COX-2). The antioxidant ability was assessed by measuring catalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels in both edema and ulcer models. Additionally, gastric lesions were detected in the ulcer and low Ulcer index confirmed anti-ulcer ability. These results suggest new benzothiazoles which can be further analyzed through clinical studies.

Abstract

Despite the significant potential of photodynamic therapy (PDT) in cancer treatment, further refinement is needed to address challenges such as poor tumor-specific accumulation of photosensitizers and the development of therapeutic resistance, which may be regulated by epigenetics. Here, a novel tumor microenvironment-responsive delivery platform was developed to co-deliver epigenetic protein degraders and photosensitizers, aiming to block the relevant regulatory mechanisms and enhance the effectiveness of combination therapy. Benefiting from the targeting ability, pH-triggered charge reversal, and intracellular glutathione (GSH)-responsive release, the delivery platform exhibited enhanced tumor accumulation and therapeutic effects. The mechanism of action revealed that the precise accumulation and release of drugs via the tumor-orchestrated delivery system not only regulated cell growth and immune activation, but also inhibited the expression of tumor immune escape molecules (PDL1 and CD47) and M2 macrophage polarization, significantly increasing the anti-breast cancer and anti-melanoma effects of PDT in the presence of an epigenetic modifier. More importantly, we found for the first time that photodynamic therapy can generate therapeutic resistance through the upregulation of CCL5, and confirmed that this resistance can be reduced by the epigenetic degradation of bromodomain-containing protein 4 (BRD4). These findings underscore the potential of integrating PDT with epigenetic protein degraders through a programmed delivery platform, offering a promising strategy for improving cancer treatment outcomes.

Abstract

The nonconventional yeast, Yarrowia lipolytica, is a promising protein expression host, having achieved recombinant protein expression yield on par with the commonly used host, Komagatella phaffii (Pichia pastoris). However, strong, fully constitutive genetic elements and expression cassettes for protein expression in Y. lipolytica remain limited. In this study, we leveraged genome-wide transcriptomics to uncover five strong promoters and four terminators. Among these, the promoter of ribosomal protein L41 demonstrated superior activity to the strongest previously reported promoters. We further demonstrated the functionality of pL41 across different media conditions and by using it to express diverse heterologous proteins. Similarly, we showed that the terminator of glutathione-S-transferase (tGST) supported higher protein expression and low transcriptional readthrough compared to commonly used terminators. To support protein secretion efforts, we utilized a secretomics-guided signal peptide screen to unveil three signal peptides, demonstrating broad applicability to different proteins. Integrating these genetic elements into a new expression cassette (YALI-pSTOmics1) resulted in a 3-fold increase in secretory expression of bovine fibroblast growth factor 2 compared to a combination of the best available state-of-the-art genetic tools for gene expression in Y. lipolytica. This expression cassette represents an open-source alternative to expensive commercial ones. Furthermore, the novel promoters and terminators provide options for metabolic engineering, where reuse of existing genetic parts is often a limitation.

Abstract

Cancer development is driven by diverse genetic aberrations, underscoring the importance of innovative approaches like gene therapy for effective treatment. The CRISPR/Cas9 gene-editing system has all the makings of a game-changing technique for future disease treatment, owing to its pinpoint accuracy and efficiency in deleting disease-causing genes or correcting damaging base mutations. A number of efficient Cas9 variants and derivatives were recently designed to tackle the intricate genomic modifications that accompany illnesses. In addition, CRISPR/Cas9 based systems are increasingly explored for biomarker sensing and cancer diagnostics. Early identification, real-time monitoring, and therapy stratification are made possible by CRISPR-driven biosensors, which can detect circulating tumor DNA, microRNAs, or exosomal RNA with high specificity and sensitivity. Furthermore, a variety of stimuli-responsive delivery strategies, including chemical and peptide-assisted systems, light-activated mechanisms, glutathione-sensitive carriers, and pH-responsive platforms, have been explored to improve intracellular release efficiency thereby enhancing the precision of CRISPR/Cas9-mediated gene editing in cancer therapy. The CRISPR/Cas9-enabled theranostic platforms employ engineered nanocarriers to simultaneously deliver gene-editing tools and imaging agents, thereby facilitating synchronized treatment monitoring and improved therapeutic precision. This review emphasizes the transformative potential of CRISPR/Cas9-integrated theranostics, which combine targeted gene editing with advanced imaging for enhanced therapeutic monitoring and efficacy in cancer treatment.