Cysteine Levels Research Articles

Holter ECG monitoring and platelets characteristics in patients with coronary artery disease and atrial fibrillation.

Aim: To check the relationships between platelet characteristics and Holter ECG monitoring results in patients with atrial fibrillation (AF) and coronary artery disease (CAD). Materials and Methods: 300 investigated patients were separated into three groups: I (CAD) - 149 patients with CAD without arrhythmias, II (CAD and AF) - 124 patients with CAD and AF paroxysm, and the control group (CG) - 27 patients without CAD and arrhythmias. Results: In the II group was detected an increase in mean platelet volume (MPV) (9.30%) and platelet-to-leucocyte ratio (PLR) (41.12%) and a decrease in platelet count (PC) (12.20%) in comparison with the I group, P<0.05. Also, in the II group was found an increase in platelet leucine (12.63%), isoleucine (10.73%), and a decrease in serine (5.06%), threonine (23.05%), valine (30.83%), glycine (32.21%) levels in comparison with the I group, P<0.05. PC, MPV, and PLR ratios were correlated with supraventricular extrasystoles per hour (r=-0.352, r=0.308, and r=0.359, consequently), P<0.05. Platelets distribution width (PDW) was correlated with ST-segment changes (r=0.371), P<0.05. Platelet threonine, serine, glycine, alanine, and valine levels were correlated with total supraventricular extrasystoles (r=-0.374, r=-0.358, r=-0.402, r=-0.307, r=-0.312, consequently) and supraventricular extrasystoles per hour (r=-0.374, r=-0.358, r=-0.402, r=-0.307, r=-0.312, consequently), P<0.05. Platelet lysine, taurine, cysteine, and phenylalanine levels were correlated with ST-segment changes (r=-0.319, r=-0.344, r=-0.376, and r=0.317, consequently), P<0.05. Conclusions: Platelet features (PC, MPV, PDW, PLR, and amino acid spectrum) are significantly correlated with supraventricular arrhythmias and ST-segment episodes, which shows their role in AF and CAD pathogenesis.

Methionine Dependence of Hair Maintenance in C57BL/6 Mice.

Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation. Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography. After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine. Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem cells.

Substituting green light for partial red light promoted the growth and quality, and regulated the nitrogen metabolism of Medicago sativa grown under red-blue LEDs

Light quality can affect the growth of plants, regulate the accumulation and metabolism of substances, thereby improving the growth and quality of plants. Alfalfa is a vital forage with wide distribution and high value for feeding. However, few studies have investigated the effects of light quality on growth, quality, and nitrogen (N) metabolism regulation of alfalfa under artificial light control environment. In this study, the light intensity was 400 μmol·m−2·s−1 and photoperiods was 16/8 h. Five light quality treatments were used for alfalfa production, red-blue ratio of 3:1, 4:1 and 5:1, respectively, and on the basis of red-blue ratio of 4:1, 5% and 10% red light were replaced by green light were also used (R3B1, R4B1, R5B1, R19B5G1 and R18B5G2). The results showed that although the stomatal conductance and lysine content of the R3B1 treatment were significantly higher than other treatments, but the leaf area, fresh yield, contents of soluble sugar, sucrose, nitrate and ammonium, as well as the enzyme activities of NR, NiR, GOGAT and GS were the lowest among all treatments. The R3B1 treatment resulted in growth inhibition and reduced N metabolism levels. Strikingly, compared with the R4B1 treatment, the synthesis of Chl a+b, Chl a, Chl b, and free amino acid, as well as the accumulation of nitrate and crude protein, and the activity of GS also increased significantly in the two treatments which green light replaced partial of red light. However, the contents of soluble sugar, glutamate and lysine, as well as the activities of GOGAT and GDH, were significantly reduced in the R19B5G1 and R18B5G2 treatments. The carotenoids and sucrose contents of R19B5G1 treatment were significantly higher than R4B1 treatment, and the fresh weight and NR activity of R18B5G2 were significantly higher than R4B1 treatment. In addition, the content of starch and soluble protein and AK activity were not affected by light quality. In general, green light instead of partial red light increased the content of photosynthetic pigment and promoted the growth of alfalfa. Although the levels of glutamate, cysteine and lysine were reduced, it was beneficial to the accumulation of nitrate, free amino acid and crude protein, maintained the stability of N metabolism and improved the feeding value. These findings provide valuable insight into the effects of light quality regulation on value of feeding and N metabolism of alfalfa.

Heterogeneity in Disulfide Bond Reduction in IgG1 Antibodies Is Governed by Solvent Accessibility of the Cysteines.

We studied unpaired cysteine levels and disulfide bond susceptibility in four different γ-immunoglobulin antibodies using liquid chromatography-mass spectrometry. Our choice of differential alkylating agents ensures that the differential peaks are non-overlapping, thus allowing us to accurately quantify free cysteine levels. For each cysteine residue, we observed no more than 5% to be unpaired, and the free cysteine levels across antibodies were slightly higher in those containing lambda light chains. Interchain and hinge residues were highly susceptible to reducing stresses and showed a 100-1000-fold higher rate of reduction compared to intrachain cysteines. Estimations of the solvent-accessible surface for individual cysteines in IgG1, using an implicit all-atom molecular dynamics simulation, show that interchain and hinge cysteines have >1000-fold higher solvent accessibility compared to intrachain cysteines. Further analyses show that solvent accessibility and the rate of reduction are linearly correlated. Our work clearly establishes the fact that a cysteine's accessibility to the surrounding solvent is one of the primary determinants of its disulfide bond stability.

Proximate Analysis of the Paste of Three Varieties of Peanuts (Arachis Hypogaea) Consumed in Côte D’ivoire

Peanuts (Arachis hypogaea) since colonization have been an obligatory crop in Ivory Coast. It is currently the culture of women par excellence in the North of Côte d'Ivoire and especially in Korhogo. Almost the entire production is consumed on site and mainly in the form of peanut paste. The objective of this study is to determine the nutritional composition of peanut pastes of three varieties produced in Côte d'Ivoire. To achieve this, three varieties of peanut were studied and named according to their morphological characteristics (large striated shell (Gcs), medium striated shell (Mcs) and small smooth shell (Pcl). These grains were transformed into paste then subjected to analyzes to know their physicochemical characteristics. The results of statistical analysis showed significant differences at P  0.05. The variety that contains the least water is (Pcl), it will better resist microbial proliferation. Gcs peanut paste was much richer in fat with a value of 45.088  0.19% and also contained myristic acid (2.976  0.008%) and linolenic acid (0.263  0.002%). As for the Pcl variety, the linoleic and oleic acid contents were dominant compared to the other varieties respectively with values of 1.139  0.006 and 0.412  0.002%. Furthermore, regarding proteins, the Pcl variety presented a high level of proteins (29.00  1.75%), however, arginine, methionine, cysteine and glutamic acid are absent.

Unraveling Antioxidative Metabolic Pathways in Multiple Myeloma: Augmenting IMiD Sensitivity through Intracellular Cysteine Biosynthesis Inhibition

Introduction Multiple myeloma (MM) patients often become unresponsive to immunomodulatory drugs (IMiDs) over time. Research has indicated that the cellular ability to counteract oxidative stress plays a crucial role in determining the sensitivity to IMiDs in MM. This study aims to comprehend the metabolic pathways responsible for MM's antioxidative capability and develop new treatments to augment the effectiveness of IMiDs. Methods We experimented using MM cells to investigate how different nutrient conditions affect cell proliferation and drug response. We utilized stable isotope-labeled amino acids and mass spectrometry to analyze the metabolites in these cells. We evaluated cell viability through the MTT assay, the CellTiter-Glo® Luminescent Assay, and direct cell counting. Furthermore, we conducted Western blots to measure the levels of various proteins expressed in MM cells grown under different nutrient conditions. To create CRBN knockout cells, we employed the CRBN CRISPR/Cas9 KO plasmid, and for the overexpression of CRBN in MM cells, we used a lentivirus system. Results Our research findings reveal that the production of cellular cysteine enhances the cell's ability to counteract oxidative damage, leading to resistance to IMiDs even with the presence of the wild-type CRBN protein. However, MM cells not producing enough cysteine rely on consuming extracellular cystine, which increases sensitivity to lenalidomide and reduces antioxidative capacity. Lenalidomide-sensitive cells acquire more cystine from the extracellular environment than resistant cells. The analysis of cysteine uptake in various MM cell lines using C13-labeled cysteine revealed that the lenalidomide-sensitive cell line, OCIMY5-CRBN, consumed more cysteine from the media, and the presence of L-glutamine further increased this uptake. Lenalidomide treatment increased the catabolism of cysteine into taurine in sensitive cell lines, confirming the link between lenalidomide's molecular action and cysteine catabolism. Our study also identified that lenalidomide treatment led to an accumulation of CDO protein, which adds molecular oxygen to cysteine, transforming it into cysteine sulfinic acid. Our study suggests that CRBN may play a role in maintaining intracellular CDO protein levels, and the accumulation of CDO protein induced by lenalidomide is the molecular factor responsible for cystine catabolism and sensitivity to IMiDs in multiple myeloma. We found that by inhibiting intracellular cysteine biosynthesis, we could improve the effectiveness of IMiD against MM. One drug that can achieve this is 5-aza-2-deoxycytidine (DAC), which acts as a DNA methylation inhibitor. Additionally, combining DAC with IMiDs improves their effectiveness, even in cell lines that are resistant to treatment. Furthermore, we attempted to inhibit cysteine biosynthesis by promoting the synthesis of methionine from homocysteine with the supplementation of 5-methyltetrahydrofolate. We discovered that treatment with 5-methyltetrahydrofolate further enhanced the sensitivity of IMiDs in resistant MM cell lines. Our results confirm that interfering with intracellular cysteine biosynthesis is a promising therapeutic approach for MM and can improve the effectiveness of IMiDs. Conclusions The biosynthesis of L-Cysteine is vital for the cellular ability to resist oxidation. Cancer cells that create high levels of cysteine within the cell from methionine generate a more significant amount of reduced cysteine, which can act as antioxidants and make MM cells resistant to IMiDs. On the other hand, cells that cannot produce enough cysteine increase their consumption of extracellular cystine and are more susceptible to IMiDs. Cells that consume an oxidized form of cystine from outside the cell require a reduction process inside the cell, which further reduces their ability to resist oxidation. Additionally, the accumulation of CDO protein induced by lenalidomide can enhance the breakdown of intracellular cysteine and cystine uptake in vulnerable cells. Overall, MM cells that rely on extracellular cysteine are sensitive to IMiDs. Therefore, interfering with intracellular cysteine biosynthesis is a better option for myeloma treatment and enhancing the sensitivity of IMiDs.

The Role of Glutathione and Sulfhydryl Groups in Cadmium Uptake by Cultures of the Rainbow Trout RTG-2 Cell Line.

The aim of this study is to investigate the role of cellular sulfhydryl and glutathione (GSH) status in cellular cadmium (Cd) accumulation using cultures of the rainbow trout cell line RTG-2. In a first set of experiments, the time course of Cd accumulation in RTG-2 cells exposed to a non-cytotoxic CdCl2 concentration (25 μM) was determined, as were the associated changes in the cellular sulfhydryl status. The cellular levels of total GSH, oxidized glutathione (GSSG), and cysteine were determined with fluorometric high-performance liquid chromatography (HPLC), and the intracellular Cd concentrations were determined with inductively coupled plasma mass spectrometry (ICP-MS). The Cd uptake during the first 24 h of exposure was linear before it approached a plateau at 48 h. The metal accumulation did not cause an alteration in cellular GSH, GSSG, or cysteine levels. In a second set of experiments, we examined whether the cellular sulfhydryl status modulates Cd accumulation. To this end, the following approaches were used: (a) untreated RTG-2 cells as controls, and (b) RTG-2 cells that were either depleted of GSH through pre-exposure to 1 mM L-buthionine-SR-sulfoximine (BSO), an inhibitor of glutathione synthesis, or the cellular sulfhydryl groups were blocked through treatment with 2.5 μM N-ethylmaleimide (NEM). Compared to the control cells, the cells depleted of intracellular GSH showed a 25% reduction in Cd accumulation. Likewise, the Cd accumulation was reduced by 25% in the RTG-2 cells with blocked sulfhydryl groups. However, the 25% decrease in cellular Cd accumulation in the sulfhydryl-manipulated cells was statistically not significantly different from the Cd accumulation in the control cells. The findings of this study suggest that the intracellular sulfhydryl and GSH status, in contrast to their importance for Cd toxicodynamics, is of limited importance for the toxicokinetics of Cd in fish cells.

Gestodene causes masculinization of the western mosquitofish (Gambusia affinis): Insights from ovary metabolomics

Gestodene (GES) is a common synthetic progesterone frequently detected in aquatic environments. Chronic exposure to GES can cause masculinization of a variety of fish; however, whether metabolism is closely related to the masculinization has yet to be explored. Hence, the ovary metabolome of adult female western mosquitofish (Gambusia affinis) after exposing to GES (0.0, 5.0, 50.0, and 500.0 ng/L) for 40 days was analyzed by using high-performance liquid chromatography ionization with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). The results showed that GES increased the levels of cysteine, taurine, ophthalmic acid and cAMP while decreased methionine, these metabolites changes may owing to the oxidative stress of the ovaries; while taurcholic acid and uric acid were decreased along with induced oocyte apopotosis. Steroids hormone metabolism was also significantly affected, with progesterone and cortisol being the most affected. Enzyme-linked immunoassay results showed that estradiol levels were decreased while testosterone levels were increased with GES exposure. In addition, correlation analysis showed that the differential metabolites of some amino acids (e.g. leucine) were strongly correlated with the levels of steroids hormones secreted by the pituitary gland. The results of this study suggest that GES affects ovarian metabolism via the hypothalamus-pituitary-gonad and hypothalamic-pituitary-adrenal axes, impair antioxidant capacity, induce apoptosis in the ovary of G. affinis, and finally caused masculinization.

Gigantol exerts anti-lung cancer activity by inducing ferroptosis via SLC7A11-GPX4 axis

Gigantol, a naturally occurring dibenzyl compound derived from various orchid species within the Dendrobium genus, exhibits notable pharmacological activity. We found that gigantol has significant anti-lung cancer properties, both in vitro and in vivo, which it exerts through the induction of ferroptosis. Furthermore, we found gigantol's specific interaction with the subunit solute carrier family 7 member 11 (SLC7A11) within the cystine/glutamate antiporter system (system Xc−), leading to the inhibition of glutathione (GSH) synthesis. This, in turn, disrupts redox homeostasis. Additionally, gigantol hinders the uptake of extracellular cystine via lung cancer cells, resulting in reduced cellular levels of cysteine, a vital precursor in GSH synthesis. This reduction, in turn, leads to an increase in the levels of glutamate. Simultaneously, our study reveals that the decrease in GSH significantly inhibits the activity of glutathione peroxidase 4 (GPX4), a key enzyme within the antioxidant system. Remarkably, N-acetylcysteine, a cystine precursor, effectively reverses gigantol-induced ferroptosis in lung cancer cells. This provides further confirmation that the anti-lung cancer mechanism of gigantol is to induce ferroptosis of lung cancer cells by targeting the SLC7A11-GPX4 signaling axis. In conclusion, our study underscores gigantol's potential as a promising candidate drug for the treatment of patients with lung cancer in clinical practice.

Development of low-cost in-house tetra-ARMS-PCR assay for the screening of five CBS mutations found in Pakistani homocystinuria patients

Background Classical homocystinuria is an inborn amino acid metabolism disorder resulting from mutations in the Cystathionine-β-Synthase (CBS) gene. These mutations lead to elevated homocysteine and methionine levels and reduced cysteine levels in the blood. Typically, diagnosis occurs after patients display symptoms, and various lab methods confirm it. DNA sequencing is the best option for early detection of genetic variants in asymptomatic suspected individuals. Unfortunately, its high cost can hinder its use, especially in low-income countries like Pakistan. Objective Aim of this study was to devise a robust low-cost diagnostic/screening assay based on Tetra-ARMS-PCR for five prevalent genetic variants found in Pakistani classical homocystinuria patients. Materials and methods In the current study, T-ARMS-PCR assays were developed for five mutations (c.975G > C, c.770C > T, c.752T > C, c.1039 + 1G > T, c.451 + 1GG > TA), which were characterized previously in classical homocystinuria patients. These low-cost T-ARMS-PCR assays were then used to screen the affected individuals and their family members to identify their genotypes for pathogenic variations in the asymptomatic patients and carriers in their respective families. Results The outcomes were entirely consistent with those obtained from Sanger DNA sequencing, confirming the sensitivity, specificity, and reliability of the T-ARMS-PCR assay for detecting CBS mutations. Conclusion T-ARMS-PCR has wide applications for low-income countries for the screening and early diagnosis of asymptomatic patients and carriers in the homocystinuria affected families as well as other inherited diseases.

Design, synthesis and cell imaging of a new 3-thiolflavone fluorescent probe for biothiols

Abnormal levels of intracellular biothiol species, including glutathione (GSH), homocysteine (Hcy), and cysteine (Cys), are closely relevant to a variety of diseases. In this study, we first report the design and synthesis of a 3-thiolflavone-based probe 3-STF with an S–S linkage both as the fluorescence quenching agent and the recognition site. Upon treatment with biothiols, the S–S linkage was cleaved by nucleophilic attack of RS-, and 3-STF exhibited a specific “turn-on” fluorescence response at 543.8 nm upon 390 nm excitation. Meanwhile, 3-STF was proved to be highly sensitive and selective for the detection of biothiols over other nucleophiles such as amino acids and H2S. The sensing mechanism was further verified by 1H NMR and ESI-MS analysis. In addition, 3-STF with low cytotoxicity can be successfully applied to detect endogenous and exogenous biothiols in HepG-2 cells.

Thiol Cathepsins and Oxidative Modification of Stallion’s Seminal Plasma Proteins with Normal and Low Percentage of Live Spermatozoa Post Cryopreservation

Background: Stallion sperms are very sensitive to cryopreservation. Free radicals generated during cryopreservation lead to spermatozoa membrane damage, decline in their viability and change the activity of cysteine cathepsins. On the other hand, cathepsins may involve in the utilization of oxidatively modified proteins. The present study was conducted to assess cysteine cathepsins activity and level of oxidatively modified proteins in seminal plasma of stallions with a low ( less than 30%) and normal ( greater than 30%) percentage of live spermatozoa post cryopreservation Methods: A total of 33 breeding stallions comprising 6 stallions of the Budennovskaya breed, 22 Arabian breed, 4 Soviet Heavy-Draft and 1 Bashkir breed. We assessed standard quality parameters in fresh and cryopreserved sperm, as well as cysteine cathepsins B,L,H activity, the level of oxidatively modified proteins in stallions seminal plasma with a low ( less than 30%) and normal ( greater than 30%) percentage of live spermatozoa post cryopreservation. Result: The group with a low percentage of live spermatozoa was characterized by decreased sperm quality, increased level of aldehyde dinitrophenylhydrazones (p=0.045) and ketone dinitrophenylhydrazones (p=0.049) of a neutral nature, as well as increased activity of cathepsin L (p=0.029). Evaluation of activity of cathepsin L and the concentration of oxidatively modified proteins in the seminal plasma can serve as a marker in the selection of stallions for sperm cryopreservation.

Paracetamol (acetaminophen) poisoning: The early years.

Paracetamol (acetaminophen) was marketed in the 1950s as a nonprescription analgesic/antipyretic without any preclinical toxicity studies. It became used increasingly for self-poisoning, particularly in the UK and was belatedly found to cause acute liver damage, which could be fatal. Management of poisoned patients was difficult as maximum abnormalities of liver function were delayed for 3days or more after an overdose. There was no treatment and the mechanism of hepatotoxicity was not known. The paracetamol half-life was prolonged with liver damage occurring when it exceeded 4h and the Rumack-Matthew nomogram was an important advance that allowed stratification of patients into separate zones of risk. It is used to guide prognosis and treatment and its predictive value could be increased by combining it with the paracetamol half-life. The problems of a sheep farmer in Australia in the early 1970s led to the discovery of the mechanism of paracetamol hepatotoxicity, and the first effective treatment of overdosage with intravenous (IV) cysteamine. This had unpleasant side effects and administration was difficult. N-acetylcysteine soon became the treatment of choice for paracetamol overdose and given early it was very effective when administered either IV or orally. N-acetylcysteine could cause anaphylactoid reactions, particularly early during IV administration when the concentrations were highest. Simpler and shorter regimes with slower initial rates of infusion have now been introduced with a reduced incidence of these adverse effects. In addition, there has been a move to use larger doses of N-acetylcysteine given over longer periods for patients who are more severely poisoned and those with risk factors. There has been much interest recently in the search for novel biomarkers such as microRNAs, procalcitonin and cyclophilin that promise to have greater specificity and sensitivity than transaminases. Paracetamol-protein adducts predict hepatotoxicity and are specific biomarkers of toxic paracetamol metabolite exposure. Another approach would be measurement of the plasma levels of cysteine and inorganic sulfate. It is 50 years since the first effective treatment for paracetamol poisoning and, apart from liver transplantation, there is still no effective treatment for patients who present late.

Lysosome-targeted fluorescence probe for discriminating cysteine from homocysteine/glutathione and assessing autophagy in drug-induced liver injury

Autophagy inhibition is an early cause of drug-induced liver injury (DILI). Cysteine (Cys) levels in lysosomes are associated with autophagy. Detecting Cys in lysosomes visually is a new requirement for DILI early diagnosis and efficacy assessment. Hence, the development of excellent fluorescent probes that can detect Cys in lysosomes with reliability, selectivity, and sensitivity is needed. In this work, a lysosome-targeted fluorescent probe LTCP for discriminating Cys from Hcy/GSH has been developed based on the sulfonylbenzoxadiazole (SBD) chromophore containing a morpholine moiety. Encounter of LTCP with Cys will trigger a sequential aromatic substitution-rearrangement reaction yielding an amino SBD derivative product and generate an obvious orange response fluorescence (λex/λem: 440/583 nm), while encounter with Hcy/GSH forms an alksulfydryl SBD derivative product via one-step aromatic substitution reaction and elicits a clear different green fluorescence (λex/λem: 400/520 nm). With the help of confocal fluorescence imaging using probe LTCP, an increase of lysosomal Cys level is observed after Rapa activates autophagy, whereas Cys concentration decreases after 3-MA inhibits autophagy in HepG2 cells. Additionally, LTCP was successfully applied for high-fidelity imaging of Cys changes in autophagy during liver injury induced by acetaminophen (APAP).

Unexpected dual-functional cyanine fluorophores: NIR multifunctional fluorescent probes for simultaneous monitoring of mitochondrial cysteine /viscosity during kidney ferroptosis in vivo

Cysteine (Cys) level and mitochondrial viscosity are important factors controlling cellular lipid peroxide metabolism and are closely related to ferroptosis. However, simultaneous tracking of these two key target analytes in the context of ferroptosis has not been realized. In this study, we developed a series of novel NIR dual-functional cyanine fluorophores AR-Cy based on a modified Vilsmeier-Haack reaction for simultaneous visualizing of cysteine level and mitochondrial viscosity during kidney ferroptosis in vivo. Intriguingly, this modified Vilsmeier-Haack reaction provides additional electron-withdrawing molecular rotor for improving the sensing performance to Cys and mitochondrial viscosity at two separated fluorescence channels (λem = 650 nm, Cys; λem = 710 nm, viscosity). Notably, by dual-color fluorescent imaging with this excellent probe AR-Cy-3, we found that ferroptosis process (erastin, sorafenib and sulfasalazine as ferroptosis inducers) was accompanied by a slight decrease in Cys channel and a significant increase in mitochondrial viscosity channel for the first time. More importantly, we further revealed that Cys level gradually decreased and mitochondrial viscosity rapidly increased in mouse kidney ferroptosis model in vivo. Therefore, this work provides not only the first dual-functional probe for studying the dynamic changes between the Cys level and mitochondrial viscosity in kidney ferroptosis but also useful cyanine fluorophores for designing powerful probes of relevant analytes to other diseases.

Effects of Exercise on Circulating Muscle-related Cytokines in Adults with Type 2 Diabetes and/or Obesity.

Skeletal muscle is an endocrine organ that plays an important role in metabolic health by secreting a variety of myokines. Recent studies have shown that exercise significantly decreases interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with type 2 diabetes (T2D). This paper explores the effect of chronic exercise on myokines in patients with T2D and/or obesity. The author searched for relevant English-language articles in PubMed. A total of 14 randomized controlled studies were found to be eligible for this short review. It has been observed that chronic exercise does not change brain-derived neurotrophic factor (BDNF), irisin, and secreted protein acidic and rich in cysteine levels, whereas it decreases TNF-α levels in patients with T2D. Combined aerobic exercise (AE) and resistance training (RT) or sprint interval training increase insulin-like growth factor 1 (IGF-1) levels and decrease IL-6 and IL-15 levels in patients with T2D. Combined AE and RT may also increase IL-15 levels in obese individuals. In addition, RT alone may increase BDNF, IGF-1, and IL-7 levels in overweight individuals. However, AE alone does not change circulating myokine levels in patients with T2D, while it may increase myonectin levels in obese individuals. This short review demonstrated that exercise appears to have favorable effects on some myokines in patients with T2D and/or obesity. However, it remains inconclusive due to the heterogeneity in subject characteristics and exercise modalities.

Sulfur metabolism in durian pulps: Factors contributing to the production of volatile sulfur compounds during fruit ripening

Durian (Durio zibethinus L.), an economically important fruit crop in Southeast Asia, is known for its strong sulfuryl aroma resulting from the accumulation of sulfur-containing compounds. However, our understanding of sulfur metabolism in fruit remains limited. In this study, we focused on the functional characterization of durian methionine γ-lyase (DzMGL), the key enzyme in volatile sulfur compound (VSC) production. In addition, to gain a better insight into sulfur metabolism, we profiled metabolites related to this process using various methods and assessed the expression of relevant genes through reverse transcription-quantitative PCR. Our gene and metabolite analyses revealed that sulfur metabolism is activated during ripening. Interestingly, DzMGL exhibited a higher efficiency in using L-cysteine than Arabidopsis MGL. The differential levels of the produced VSCs explained the aroma intensity-related differences between the two commercial Thai cultivars ‘Chanee’ and ‘Monthong’. Furthermore, the cysteine availability-related differences between the two cultivars could contribute to this variation, with ‘Chanee’ containing higher cysteine levels than ‘Monthong’. Our findings indicated that γ-glutamylcysteine was the preferred form of sulfur storage in durian pulps, with a potential recycling process providing intermediates that flux methionine toward ethylene biosynthesis and VSC production. This study provides novel insights into sulfur metabolism in durian fruit.

Pre-cut L-cysteine treatment inhibited the browning of fresh-cut apples by regulating enzyme activities and amino acid levels

This work investigated the effect of pre-cut L-cysteine treatment on the browning of fresh-cut apple slices. The results showed that 1% L-cysteine pre-cut treatment for 15 min could significantly inhibit the browning and extend the shelf life of fresh-cut apple slices. Pre-cut L-cysteine treatment was found to significantly inhibit polyphenol oxidase (PPO) activity and its gene expression, and increased superoxide dismutase (SOD) and catalase (CAT) activity as well as DPPH radical scavenging rate. In addition, pre-cut L-cysteine treatment improved the content of total and individual phenolics, particularly the content of chlorogenic acid and epicatechin in pulp. Pre-cut L-cysteine treatment also increased the cysteine, glutamic acid, serine and leucine level in pulp and peel. Therefore, pre-cut L-cysteine treatment is an effective method to control the browning of fresh-cut apple by inhibiting PPO activity, improving antioxidant ability and regulating the synthesis of phenolics and free amino acids.

GhCYS2 governs the tolerance against cadmium stress by regulating cell viability and photosynthesis in cotton

Cysteine, an early sulfur-containing compound in plants, is of significant importance in sulfur metabolism. CYS encodes cysteine synthetase that further catalyzes cysteine synthesis. In this investigation, CYS genes, identified from genome-wide analysis of Gossypium hirsutum bioinformatically, led to the discovery of GhCYS2 as the pivotal gene responsible for Cd2+ response. The silencing of GhCYS2 through virus-induced gene silencing (VIGS) rendered plants highly susceptible to Cd2+ stress. Silencing GhCYS2 in plants resulted in diminished levels of cysteine and glutathione while leading to the accumulation of MDA and ROS within cells, thereby impeding the regular process of photosynthesis. Consequently, the stomatal aperture of leaves decreased, epidermal cells underwent distortion and deformation, intercellular connections are dramatically disrupted, and fissures manifested between cells. Ultimately, these detrimental effected culminating in plant wilting and a substantial reduction in biomass. The association established between Cd2+ and cysteine in this investigation offered a valuable reference point for further inquiry into the functional and regulatory mechanisms of cysteine synthesis genes.

The kinetics of glutathione in the gastrointestinal tract of weaned piglets supplemented with different doses of dietary reduced glutathione.

This study aimed to investigate the kinetics of dietary GSH in the gastrointestinal tract and the effect of GSH on the intestinal redox status of weaned piglets. Forty-eight piglets with an average age of 26 days and an average body weight of 7.7 kg were used in this study. The piglets were divided into three treatment groups including the control group with a basal diet (CON) and two GSH groups with a basal diet supplemented with 0.1% GSH (LGSH) and 1.0% GSH (HGSH), respectively. The basal diet did not contain any GSH. The experiment lasted for 14 days, with eight animals sampled from each group on d5 and 14. The parts of 0-5%, 5-75%, and 75-100% of the length of the small intestine were assigned to SI1, SI2, and SI3. The results showed that GSH almost completely disappeared from the digesta at SI2. However, no difference in the GSH level in mucosa, liver, and blood erythrocytes was found. The level of cysteine (CYS) in SI1 digesta was significantly higher in HGSH than CON and LGSH on d14, and similar findings were observed for cystine (CYSS) in SI3 digesta on d5. The CYSS level in HGSH was also significantly higher than LGSH in the stomach on d14, while no CYS or CYSS was detected in the stomach for control animals, indicating the breakdown of GSH to CYS already occurred in the stomach. Irrespective of the dietary treatment, the CYS level on d14 and the CYSS level on d5 and 14 were increased when moving more distally into the gastrointestinal tract. Furthermore, the mucosal CYS level was significantly increased at SI1 in the LGSH and HGSH group compared with CON on d5. Glutathione disulfide (GSSG) was recovered in the diets and digesta from the LGSH and HGSH group, which could demonstrate the auto-oxidation of GSH. It is, therefore, concluded that GSH supplementation could not increase the small intestinal mucosal GSH level of weaned piglets, and this could potentially relate to the kinetics of GSH in the digestive tract, where GSH seemed to be prone to the breakdown to CYS and CYSS and the auto-oxidation to GSSG.