Oxidase Activity Research Articles

Pre-harvest foliar spraying of calcium and zinc preserves berries quality and mitigates chilling injury of grape during cold storage

The current study was conducted to elucidate the effect of single and combined post-veraison sprays of calcium nitrate (Ca, 2 %) and zinc sulfate (Zn, 1 %) on post-harvest quality attributes of ‘Sahebi’ grapes during cold storage. Grapes foliar-sprayed with combination of Ca and Zn showed higher flavonols (28 % myricetin, 4 % quercetin, and 15 % kaempferol), flavanols (6 % catechin, 29 % epicatechin, and 10 % epi‑gallocatechin) and anthocyanins (21 % malvidin, 16 % cyaniding and 13 % peonidin, 22 % petunidin) than controls. Moreover, Ca and Zn foliar application was also effective in preserving the levels of trans-resveratrol and phenolic acids in grape berries. The higher amount of phenolic compounds in Ca + Zn-treated grapes was accompanied with higher activity of antioxidant enzymes, lower activity of polyphenol oxidase, and lower incidence of fungal decay. In general, post veraison spray of Ca and Zn is promising viticultural operation for preserving berries bioactive compound and mitigating chilling injury of grape during cold storage.

Protective Effect of Coated Benzoic Acid on Intestinal Epithelium in Weaned Pigs upon Enterotoxigenic Escherichia coli Challenge.

The study was designed to investigate the protective effect of dietary supplementation with coated benzoic acid (CBA) on intestinal barrier function in weaned pigs challenged with enterotoxigenic Escherichia coli (ETEC). Thirty-two pigs were randomized to four treatments and given either a basal diet or a basal diet supplemented with 3.0 g/kg CBA, followed by oral administration of ETEC or culture medium. The results showed that CBA supplementation increased the average daily weight gain (ADWG) in the ETEC-challenged pigs (p < 0.05). CBA also increased the serum activity of total superoxide dismutase (T-SOD) and the total antioxidant capacity (T-AOC), as it decreased the serum concentrations of endotoxin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the ETEC-challenged pigs (p < 0.05). Interestingly, the CBA alleviated the ETEC-induced intestinal epithelial injury, as indicated by a reversal of the decrease in D-xylose absorption and a decrease in the serum levels of D-lactate and diamine oxidase (DAO) activity, as well as a decrease in the quantity of apoptotic cells in the jejunal epithelium following ETEC challenge (p < 0.05). Moreover, CBA supplementation significantly elevated the mucosal antioxidant capacity and increased the abundance of tight junction protein ZO-1 and the quantity of sIgA-positive cells in the jejunal epithelium (p < 0.05). Notably, CBA increased the expression levels of porcine beta defensin 2 (PBD2), PBD3, and nuclear factor erythroid-2 related factor 2 (Nrf-2), while downregulating the expression of toll-like receptor 4 (TLR4) in the jejunal mucosa (p < 0.05). Moreover, CBA decreased the expression levels of interleukin-1β (IL-1β), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) in the ileal mucosa upon ETEC challenge (p < 0.05). These results suggest that CBA may attenuate ETEC-induced damage to the intestinal epithelium, resulting in reduced inflammation, enhanced intestinal immunity and antioxidant capacity, and improved intestinal epithelial function.

An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.

Candida albicans is a ubiquitous fungus in the human gut microbiome as well as a prevalent cause of opportunistic mucosal and systemic disease. There is currently little understanding, however, as to how crosstalk between C. albicans and the host regulates colonization of this key niche. Here, we performed expression profiling on ileal and colonic tissues in germ-free mice colonized with C. albicans to define the global response to this fungus. We reveal that Duox2 and Duoxa2 , encoding dual NADPH oxidase activity, are upregulated in both the ileum and colon, and that induction requires the C. albicans yeast-hyphal transition and the hyphal-specific toxin candidalysin. Hosts lacking the IL-17 receptor failed to upregulate Duox2/Duoxa2 in response to C. albicans , while addition of IL-17A to colonoids induced these genes together with the concomitant production of hydrogen peroxide. To directly define the role of Duox2/Duoxa2 in fungal colonization, antibiotic-treated mice lacking intestinal DUOX2 activity were evaluated for C. albicans colonization and host responses. Surprisingly, loss of DUOX2 function reduced fungal colonization at extended time points (>17 days colonization) and increased the proportion of hyphal cells in the gut. IL-17A levels were also elevated in C. albicans -colonized mice lacking functional DUOX2 highlighting cross-regulation between this cytokine and DUOX2. Together, these experiments reveal novel links between fungal cells, candidalysin toxin and the host IL-17-DUOX2 axis, and that a complex interplay between these factors regulates C. albicans filamentation and colonization in the gut.

Dietary xylo-oligosaccharides alleviates LPS-induced intestinal injury via endoplasmic reticulum-mitochondrial system pathway in piglets.

The beneficial effects of xylo-oligosaccharides (XOS) on the intestine have been widely reported, including anti-inflammation, antioxidant, maintenance of intestinal epithelial barrier, and treatment of intestinal injury. However, the specific mechanism of XOS in mitigating intestinal injury in weaned piglets remains unclear. Therefore, this study aimed to explore the specific mechanism of XOS in mitigating intestinal injury. The study is a complete randomized design with 24 weaned piglets in a 2 × 2 factorial arrangement that includes diet treatments (basal diet vs 0.02% XOS) and immunological challenge [saline vs lipopolysaccharide (LPS)]. All piglets were fed a basal diet or a XOS diet for 21 days. On day 22, all piglets received an injection of LPS or saline. In this study, dietary XOS increased jejunal villus height, reduced crypt depth and oxidative stress, and enhanced the gene and protein expression of Claudin-1, Occludin, and zonula occludens 1 (P < 0.05). The piglets fed the XOS diet had lower serum Diamine oxidase activity and D-lactic acid content (P < 0.05). In addition, dietary XOS regulates endoplasmic reticulum (ER)-mitochondria system function and the expression of key molecules, including mitochondrial dynamics dysfunction [mitofusin (Mfn)-1, optic atrophy 1, fission 1, and dynamin-related protein 1], ER stress [activating transcription factor 4 (ATF4), ATF6, C/EBP homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, GRP94 and protein kinase R-like ER kinase] and the mitochondria-associated ER membranes (MAM) disorders (Mfn2, GRP75 and voltage-dlependent anion channel 1) (P < 0.05). Therefore, the findings to indicate that dietary XOS is effective against LPS-induced jejunal injury may be attributed to its ability to alleviate mitochondrial dynamics dysfunction, ER stress, and MAM disorders.

Exogenous inoculation of Pediococcus pentosaceus SSC12 positively regulates anthocyanin biosynthesis to alleviate browning of postharvest litchi (Litchi chinensis Sonn.)

Litchi is prone to pericarp browning after-harvest, which seriously affects the quality of litchi and causes huge loss. Pericarp browning is closely related to anthocyanin metabolism. Lactic acid bacteria (LAB), a kind of probiotics, is used for food preservation. The aim of this study was to investigate whether and how inoculation of LAB strain Pediococcus pentosaceus SSC12 of litchi fruit affect the pericarp browning and anthocyanin metabolism in postharvest through transcriptome and metabolome analyses. This is the first work showing that strain SSC12 suppressed development of browning and maintained the coloration of litchi pericarp at 10 ± 1 °C. Strain SSC12 upregulated 8 key differentially expressed genes (DEGs) associated with anthocyanin biosynthesis and transport, while downregulated 3 key DEGs involved in anthocyanin degradation in anthocyanin synthesis pathway. Strain SSC12 caused increase in 9 different anthocyanin-related metabolites levels and phenylalanine ammonia lyase activity, disease in peroxidase, laccase and polyphenol oxidase activities. Taken together, strain SSC12 suppressed browning of litchi via elevateing anthocyanin synthesis and transport and inhibiting anthocyanin degradation. These findings suggested that strain SSC12 might serve as a potential probiotic strains to alternative for chemical reagents in postharvest fruit preservation and contribute to the exploration of newgreen approachs for postharvest losses.

Serum ceruloplasmin oxidase activity: A neglected diagnostic biomarker for Wilson disease

BackgroundLow serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied. MethodsAll patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test. ResultsSerum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61–1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %). ConclusionSerum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients.

Phenotypic assessment of Cox10 variants and their implications for Leigh Syndrome

ObjectivesCox10 is an enzyme required for the activity of cytochrome c oxidase. Humans who lack at least one functional copy of Cox10 have a form of Leigh Syndrome, a genetic disease that is usually fatal in infancy. As more human genomes are sequenced, new alleles are being discovered; whether or not these alleles encode functional proteins remains unclear. Thus, we set out to measure the phenotypes of many human Cox10 variants by expressing them in yeast cells.ResultsWe successfully expressed the reference sequence and 25 variants of human Cox10 in yeast. We quantitated the ability of these variants to support growth on nonfermentable media and directly measured cytochrome c oxidase activity. 11 of these Cox10 variants supported approximately half or more the cytochrome c oxidase activity compared to the reference sequence. All of the strains containing those 11 variants also grew robustly using a nonfermentable carbon source. Cells expressing the other variants showed low cytochrome c oxidase activity and failed to grow on nonfermentable media.

Trichoderma-Bioenriched Vermicompost Induces Defense Response and Promotes Plant Growth in Thai Rice Variety "Chor Khing".

Vermicompost (VC) produced by African nightcrawler earthworms (Eudrilus eugeniae) is a natural fertilizer with a rich microbial community. Trichoderma asperelloides PSU-P1 is an effective antagonistic microorganism with multifaceted activity mechanisms. This research aimed to develop Trichoderma-bioenriched vermicompost (TBVC) to promote plant growth and induce the defense response in the Thai rice variety "Chor Khing". T. asperelloides PSU-P1 was tested against Rhizoctonia solani, the pathogen of sheath blight disease, using a dual-culture assay. The results showed that T. asperelloides PSU-P1 effectively inhibited R. solani in vitro growth by 70.48%. The TBVC was prepared by adding a conidial suspension (108 conidia/mL) to vermicompost. The viability of Trichoderma persisted in the vermicompost for 6 months and ranged from 1.2 to 2.8 × 107 CFU/mL. Vermicompost water extracts significantly enhanced seed germination, root length, and shoot length compared to a control group (p < 0.05). Plants that received the TBVC displayed significantly longer shoot and root lengths and higher total chlorophyll content than control plants (p < 0.05). The TBVC induced defense response by increasing the enzyme activity of peroxidase (POD) and polyphenol oxidase (PPO) in comparison with control plants. Rice grown in the TBVC had a significantly reduced incidence of sheath blight caused by R. solani in comparison with control rice (p < 0.05). Furthermore, the fungal community of rice plants was analyzed via the high-throughput next-generation sequencing of the internal transcribed spacer (ITS). The fungal community in the TBVC had greater alpha diversity than the community in the VC. Phylum Ascomycota was dominant in both samples, and a heat map showed that Trichoderma was more prevalent in the TBVC than in the VC. Our results indicate that the enrichment of VC with Trichoderma increases growth, enhances the defense response, and reduces the incidence of sheath blight disease in the Thai rice variety "Chor Khing".

Integrated microbiome and metabolomic analysis of Spodoptera litura under Metarhizium flavoviride qc1401 stress.

Metarhizium spp. have emerged as an alternative to chemical pesticides for protecting crops from insect pest. Here, we investigated midgut microbial community and metabolites of Spodoptera litura at three different timepoints after infection with Metarhizium flavoviride. The innate immune system of S. litura was activated with levels of polyphenol oxidase, carboxylesterase, multifunctional oxidase, and glutathione S-transferase activity significantly increasing. Exposure to the fungal pathogen also altered bacterial abundance and diversity in host's midgut, and these changes varied depending on the time elapsed since exposure. We identified more operational taxonomic units in the treated samples as compared to the control samples at all tested time points. A total of 372 metabolites were identified, and 88, 149, and 142 differentially accumulated metabolites (DAMs) were identified between the treatment and control groups at 3 timepoints after treatment, respectively. Based on the changes of DAMs in response to M. flavoviride infection at different timepoints and significantly enriched KEGG pathways, we speculated that "tyrosine metabolism," "galactose metabolism," "ATP-binding cassette transporters," "neuroactive ligand-receptor interaction," "purine metabolism," "arginine and proline metabolism," "beta-alanine metabolism," "lysosome," and "carbon metabolism" may participate in the metabolic-level defense response. An integrated pathway-level analysis of the 16S-rDNA and metabolomic data illustrated the connections and interdependencies between the metabolic responses of S. litura and the midgut microorganisms to M. flavoviride infection. This work emphasizes the value of integrated analyses of insect-pathogen interactions, provides a framework for future studies of critical microorganisms and metabolic determinants of these interactions, establishes a theoretical basis for the sustainable use of M. flavoviride.

Long-term mulched drip irrigation facilitates soil organic carbon stabilization and the dominance of microbial stochastic assembly processes

Mulched drip irrigation (MDI) is generally accepted as a method to decrease soil salinization and improve crop yields in arid and semi-arid regions. However, there remain gaps in how MDI drives soil organic carbon (SOC) dynamic microbial assembly processes with time, and the mediating role of microorganisms remains unclear. In this study, we investigated the aforementioned issues across soil profiles in cotton fields with different years of MDI. The results showed that MDI did not cause the differences in SOC, particular organic carbon (POC), and mineral-associated organic carbon (MOC) in soil layers. The POC and MOC contents had a parabola relationship with time, and showed an opposite trend in soil. After 15 years of MDI, the ratio of MOC/SOC increased to a peak value of 50 % and 52 % in topsoil and subsoil, respectively; the ratio of POC/SOC decreased to valley values of 50 % and 48 %, respectively (P < 0.05). Long-term MDI reduced the differences in oxidase between soil layers but accelerated SOC loss by increasing polyphenol oxidase activity (P < 0.05). Compared with that of other years, with 10 years of MDI, bacterial Shannon diversity decreased to a valley value, and fungal Shannon diversity reached to a top value in subsoil (P < 0.05). In general, stochastic processes were mainly controlled by dispersal limitation, and undominated processes dominated microbial assembly; however, there was a close relationship between bacterial communities and organic carbon fractions. The high percentage of positive linkages among microorganisms indicated that long-term MDI was beneficial for carbon fixation. Additionally, a decrease of fungal oligotroph/copiotroph ratio, the relative abundance of Ascomycota and Basidiomycota was beneficial for the accumulation of SOC and POC in topsoil (P < 0.05). In conclusion, long-term MDI is useful for the fixation of organic carbon via improving soil POC content and strengthening linkages within community assemblies.

Exposure to thimerosal induces behavioral abnormality in the early life stages of zebrafish via altering amino acid homeostasis

Thimerosal (THI) has become a significant source of organic mercury pollutants in aquatic ecosystems, but there is limited information regarding its adverse effects on fish. In this study, zebrafish embryos were exposed to THI at 0 (control), 5.0, and 50 ng/L from 0–5 days post fertilization (dpf), and variations in their survival, development, behavior, free amino acid contents, and the biochemical responses involved in monoaminergic systems were examined. Although THI exposure did not significantly affect the survival, heart rate, or hatching time of zebrafish embryos, it substantially increased swimming velocity (136–154 % of the control) and reduced exploratory behavior (141–142 % of the control) in zebrafish larvae at 5 dpf. Exposure also significantly altered the amino acid contents (51–209 % of the control) and monoamine levels (70–154 % of the control) in zebrafish larvae, some of which displayed significant correlations with behavioral traits. THI significantly elevated dopamine receptor gene expression and monoamine oxidase activity in zebrafish larvae. Adding extra phenylalanine or tryptophan to the E3 medium facilitates the recovery of zebrafish larvae from the abnormal behaviors induced by THI. These findings reveal for the first time that THI exposure at the level of ng/L is sufficient to induce neurobehavioral toxic effects in the early life stages of zebrafish, and disrupting amino acid homeostasis is a critical underlying mechanism. This study provides valuable insights into the toxicity of THI to fish and highlights the importance of assessing its potential risks to aquatic ecosystems.

Vitamin C as a functional enhancer in the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab, Scylla paramamosain

This experiment was conducted to explore the effects of dietary vitamin C supplementation on non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab (Scylla paramamosain). Mud crabs with an initial weight of 14.67 ± 0.13 g were randomly divided into 6 treatments and fed diets with 0.86 (control), 44.79, 98.45, 133.94, 186.36 and 364.28 mg/kg vitamin C, respectively. The experiment consisted of 6 treatments, each treatment was designed with 4 replicates and each replicate was stocked with 8 crabs. After 42 days of feeding experiment, 2 crabs were randomly selected from each replicate, and a total of 8 crabs in each treatment were carried out 72 h low-temperature challenge experiment. The results showed that crabs fed diets with 186.36 and 364.28 mg/kg vitamin C significantly improved the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemolymph and hepatopancreas (P < 0.05). Crabs fed diet with 133.94 mg/kg vitamin C significantly decreased the concentration of nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in hemolymph (P < 0.05). Diet with 133.94 mg/kg vitamin C was improved the activity of polyphenol oxidase (PPO) and the concentration of albumin (ALB) in hemolymph. Crabs fed diet with 133.94 mg/kg vitamin C showed lower concentration of malondialdehyde (MDA) in hemolymph and hepatopancreas than those fed the other diets. Meanwhile, crabs fed diet with 98.45 mg/kg vitamin C showed higher activity of total superoxide dismutase (T-SOD) in hemolymph, and crabs fed diet with 133.94 mg/kg vitamin C showed higher activity of T-SOD in hepatopancreas. Crabs fed diet with 186.36 mg/kg vitamin C significantly decreased the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-PX) in hepatopancreas (P < 0.05). In normal temperature, crabs fed diets with 133.94 mg/kg vitamin C significantly up-regulated the expression levels of gpx (glutathione peroxidase) and trx (thioredoxin) in hepatopancreas compared with the control treatment (P < 0.05). The highest expression levels of relish, il16 (interleukin 16), caspase 2 (caspase 2), p38 mapk (p38 mitogen-activated protein kinases) and bax (bcl-2 associated x protein) in hepatopancreas were found at crabs fed control diet (P < 0.05). Moreover, crabs fed diet with 133.94 mg/kg vitamin C showed higher expression levels of alf-3 (anti-lipopolysaccharide factor 3) and bcl-2 (B-cell lymphoma 2) in hepatopancreas than those fed the other diets (P < 0.05). Under low-temperature stress, crabs fed diet with 133.94 mg/kg vitamin C significantly improved the expression levels of hsp90 (heat shock protein 90), cat (catalase), gpx, prx (thioredoxin peroxidase) and trx in hepatopancreas (P < 0.05). In addition, dietary with 133.94 vitamin C significantly up-regulated the expression levels of alf-3 and bcl-2 (P < 0.05). Based on two slope broken-line regression analysis of activity of PPO against the dietary vitamin C level, the optimal dietary vitamin C requirement was estimated to be 144.81 mg/kg for juvenile mud crab. In conclusion, dietary 133.94–144.81 mg/kg vitamin C significantly improved the non-specific immune defense, antioxidant capacity and resistance to low-temperature stress of juvenile mud crab.

JrPPO1/2 play distinct roles in regulating walnut fruit browning by different spatiotemporal expression and enzymatic characteristics

Polyphenol oxidase (PPO) activity drives walnut fruit browning, but the roles of its only two-family genes, JrPPO1 and JrPPO2, remain unclear. This study explores the spatiotemporal expression and enzymatic characteristics of JrPPO1 and JrPPO2 in walnut. Treatment with the PPO activator CuSO4 and H2O2 accelerated fruit browning and up-regulated JrPPO1/2 expression, whereas treatment with the PPO inhibitor ascorbic acid delayed browning, down-regulating JrPPO1 and up-regulating JrPPO2 expression. Compared to mJrPPO1, mJrPPO2 can exhibited better enzyme activity at higher temperatures (47 °C) and in more acidic environments (pH 4.25). mJrPPO2 exhibited a higher substrate specificity over mJrPPO1, and the preferred substrates are catechol, chlorogenic acid, and epicatechin. Additionally, mJrPPO2 adapted better to low concentration of oxygen (as low as 1.0% O2) and slightly elevated CO2 levels compared to mJrPPO1. Subcellular localization and spatiotemporal expression patterns showed that JrPPO1 is only expressed in green tissues and located in chloroplasts, while JrPPO2 is also located in chloroplasts, partly associated with membranes, and is expressed in both green and non-green tissues. Silencing JrPPO1/2 with virus-induced gene silencing (VIGS) reduced fruit browning, maintained higher total phenols, and decreased MDA production. Notably, silencing JrPPO1 had a greater impact on browning than JrPPO2, indicating JrPPO1's greater contribution to PPO activity and fruit browning in walnut fruits. Consequently, JrPPO1 can be effectively regulated both at the molecular level and by manipulating environmental conditions, to achieve the objective of controlling fruit browning.

Chemical Composition of Seeds in Soybean Glycine soja (Fabaceae) of Amur Oblast.

The wild soybean Glycine soja Sieb. et Zucc. is an ancestor of the cultivated soybean Glycine max (L.) Merr. and a source of many valuable genes missing in the G. max genome, including genes that determine stress resistance to adverse environmental factors. Biochemical parameters (protein, oil, ascorbic acid, carotene, higher fatty acids, and specific activities and multiple forms of enzymes of the oxidoreductase and hydrolase classes) were studied in five G. soja accessions from the collection of the All-Russian Institute of Soybean (КА-1413, КА-342, КBl-29, КBl-24, and Kеl-72). The accessions provide unique natural gene banks. Wild seeds were collected in three districts (Arkharinskii, Blagoveshchensk, and Belogorskii) of Amur Oblast. Based on superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO), ribonuclease (RNase), acid phosphatase, esterase, and amylase (AML) activities and biochemical parameters of seeds, the G. soja accession KA-1413 was found to have higher contents of protein, oleic acid, and linolenic acid; a lower polyphenol oxidase specific activity; and higher activities of SODs, esterases, and RNases. The accession KA-1413 was therefore recommended to use as a source of dominant genes in breeding to increase the adaptive potential of new soybean varieties. A higher heterogeneity of multiple forms was observed for SOD, AML, RNase, and esterase, which can provide markers of adaptation to environmental conditions.

Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin.

Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor. We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH. The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed. Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it. ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.

Effect of serum diamine oxidase activity derived from response to chemotherapy on adverse events and serum amino acid concentrations for esophageal cancer.

55 Background: The relationship between activity of the small intestinal villi and the effectiveness of chemotherapy remains unclear. This study aimed to investigate how serum diamine oxidase (DAO) activity affects antitumor effects, adverse events, and amino acid absorption. Methods: We performed a single-center prospective cohort study that enrolled 50 patients with esophageal cancer (EC) receiving docetaxel, cisplatin, and 5-fluorouracil therapy. We determined the cut-off value of serum DAO activity contributing to a response to chemotherapy using a generalized additive model. Additionally, we compared adverse events, inflammatory markers, blood amino acid levels, and quality of life between the high and low DAO activity groups during chemotherapy. Results: The cut-off value of serum DAO activity at the first visit that contributed to a chemotherapy response was 6.5 units/L. Leukopenia and neutropenia of Grade ≥3 were significantly higher in the DAO low (&lt;6.5 units/L) group ( p = 0.044, 0.017, respectively). Interleukin-6 was significantly lower in the DAO high (≥6.5 units/L) group at the first visit and at 4 weeks after the end of chemotherapy ( p = 0.039, 0.011, respectively). Glutamine was higher in the DAO high group at all measurement points during chemotherapy. Fatigue was significantly lower in the DAO high group ( p = 0.001). Conclusions: Serum DAO activity may be a predictor of the response to chemotherapy in patients with EC. The absorption capacity of amino acids was maintained in the group with high DAO activity, which may have contributed to the anti-inflammatory effect and provided a background for reducing adverse events. Clinical trial information: UMIN000048273 .

Pharmacodynamic profiling in three patients with molybdenum cofactor deficiency type A reveals prolonged biological effects after withdrawal of cyclic pyranopterin monophosphate

Molybdenum cofactor deficiency type A has successfully been treated in a small number of children with daily intravenous administration of cyclic pyranopterin monophosphate. Pharmacodynamic data for this novel treatment have not been published and alternative dosing intervals have not been explored. We monitored pharmacodynamic biomarkers of sulfite oxidase and xanthine oxidoreductase activity in three patients with MoCD-A for a period of 2 to 9 months after discontinuation of cPMP substitution. We found that the clinical and metabolic effects were sustained for longer than expected, over 7 days at least. Our data implicate a biological half-life of the molybdenum cofactor dependent enzyme activities of approximately 3 days and suggest the possibility that less frequent than once daily dosing intervals could be a safe alternative to current practice.

Variations in quality attributes of pulsed light-treated table grape juice during refrigerated storage (4°C) and ambient conditions (25°C).

Pulsed light (PL) pasteurization is being explored as a substitute for the conventional thermal pasteurization of juices in recent times due to better retention of nutrients and overall quality. However, the long-term stability of the PL-pasteurized juice must be investigated to promote its application by the industry. The effect of PL treatment (effective fluence of 1.15 J·cm-2) and thermal treatment (90°C for 60 s) on microbial quality, enzyme activity, bioactive compounds, sensory acceptance, and color profile of table grape juice during storage at 4 and 25°C was investigated in this study. The PL pasteurization enhanced the microbial shelf-life of the juice (<6 log10cfu·mL-1) from 5 to 35 days at 4°C. The PL and thermally-pasteurized juice demonstrated a shelf-life of only 10 days when stored at 25°C. The total soluble solids and titratable acidity did not alter significantly throughout the storage period. The peroxidase, polyphenol oxidase, and pectin methylesterase activities were below 10% for the PL and thermally-treated beverage when stored at 4°C. The sensory acceptability of the PL-pasteurized juice after 35 days of refrigerated storage (6.9±0.3) was close to the untreated juice (7.2±0.3) and greater than thermally-treated juice (6.2±0.2). After the 35th day of storage at 4°C, PL-treated grape juice retained 55%, 12%, and 15.3% more phenolics, flavonoids, and antioxidant capacity, respectively, than the thermally-pasteurized juice. Hence, PL pasteurization can effectively prolong the shelf-life of table grape juice while achieving microbial and enzymatic stability, along with high sensory and nutritional appeal. PRACTICAL APPLICATION: Exploring non-thermal methods like pulsed light (PL) pasteurization as a substitute for conventional thermal methods is gaining recognition for its ability to retain nutrients and improve overall juice quality. However, the industry's adoption depends on understanding the shelf-stability of PL-pasteurized juice. This study specifically investigates the practical applications of PL treatment in comparison with conventional thermal treatment in enhancing microbial safety and enzymatic stability in table grape juice. The findings contribute insights into optimizing the shelf life of table grape juice and preserving its quality, supported by microbial, enzymatic, and sensory evaluations.

BAG3 Mediated Down-regulation in Expression of p66shc has Ramifications on Cellular Proliferation, Apoptosis and Metastasis.

Redundancy of cancer cells towards ROS-mediated apoptosis despite expressing proline-rich p66shc abundantly needs to be investigated properly. P66shc, an adapter protein, is indispensable both for initiating ROS-mediated apoptosis and subsequent ROS generation through Rac-1 activation. P66shc gets phosphorylated at Ser-36 that triggers its translocation to the mitochondria and subsequent release of Cytochrome c in response to oxidative stress. It also aids in Rac-1 dependent NADPH oxidase activation, leading to the generation of cytosolic ROS that can perform diverse functions depending on its concentration. This study has identified the multi-faceted anti-apoptotic protein BAG3 as an interacting partner of p66shc. BAG3 utilizes its WW domain to bind to the proline-rich motifs of p66shc. BAG3, through its WW domain, antagonizes p66shc mediated apoptosis, by inhibiting both the expression and phosphorylation of p66shc under normal and oxidative stress conditions. This results in significant protection against ROS-mediated apoptosis. BAG3-mediated reduction in p66shc expression increases cell proliferation and metastasis. The increase in cell proliferation is attributed to the impact of BAG3 on Rac-1 activation and ROS production under normal conditions. This study has unraveled an interactor of p66shc that enhances pro-survival role while simultaneously suppressing its apoptotic role.

Does Bidens pilosa L. Affect Carbon and Nitrogen Contents, Enzymatic Activities, and Bacterial Communities in Soil Treated with Different Forms of Nitrogen Deposition?

The deposition of nitrogen in soil may be influenced by the presence of different nitrogen components, which may affect the accessibility of soil nitrogen and invasive plant-soil microbe interactions. This, in turn, may alter the success of invasive plants. This study aimed to clarify the influences of the invasive plant Bidens pilosa L. on the physicochemical properties, carbon and nitrogen contents, enzymatic activities, and bacterial communities in soil in comparison to the native plant Pterocypsela laciniata (Houtt.) Shih treated with simulated nitrogen deposition at 5 g nitrogen m-2 yr-1 in four forms (nitrate, ammonium, urea, and mixed nitrogen). Monocultural B. pilosa resulted in a notable increase in soil pH but a substantial decrease in the moisture, electrical conductivity, ammonium content, and the activities of polyphenol oxidase, β-xylosidase, FDA hydrolase, and sucrase in soil in comparison to the control. Co-cultivating B. pilosa and P. laciniata resulted in a notable increase in total soil organic carbon content in comparison to the control. Monocultural B. pilosa resulted in a notable decrease in soil bacterial alpha diversity in comparison to monocultural P. laciniata. Soil FDA hydrolase activity and soil bacterial alpha diversity, especially the indices of Shannon's diversity, Simpson's dominance, and Pielou's evenness, exhibited a notable decline under co-cultivated B. pilosa and P. laciniata treated with nitrate in comparison to those treated with ammonium, urea, and mixed nitrogen.