Reductase Type Research Articles

Functional analysis of the extraplastidial TRX system in germination and early stages of development of Arabidopsis thaliana

A series of processes occur during seed formation, including remarkable metabolic changes that extend from early seed development to seedling establishment. The changes associated with processes initiated mainly after seed imbibition are usually characterized by extensive modification in the redox state of seed storage proteins and of pivotal enzymes for reserve mobilization and usage. Such changes in the redox state are often mediated by thioredoxins (TRXs), oxidoreductase capable of catalyzing the reduction of disulfide bonds in target proteins to regulate its structure and function. Here, we analyzed the previously characterized Arabidopsis mutants of NADPH-dependent TRX reductase types A and B (ntra ntrb), two independent mutant lines of mitochondrial thioredoxin o1 (trxo1) and two thioredoxin h2 (trxh2) mutant lines. Our results indicate that plants deficient in the NADPH dependent thioredoxin system are able to mobilize their reserves, but, at least partly, fail to use these reserves during germination. TRX mutants also show decreased activity of regulatory systems required to maintain redox homeostasis. Moreover, we observed reduced respiration in mutant seeds and seedlings, which in parallel with an impaired energy metabolism affects core biological processes responsible for germination and early development of TRX mutants. Together, these findings suggest that the lack of TRX system induces significant change in the respiration of seeds and seedlings, which undergo metabolic reprogramming to adapt to the new redox state.

7772 A Study on Role of Anti-Mullerian Hormone and Inhibin B in 46,XY Disorders Of Sexual Development

Abstract Disclosure: N. Kudugunti: None. S. Bangaru: None. R.K. Sahay: None. Background: In pre-pubertal period, a major part of the testicular tissue is constituted by Sertoli cells for which AMH, Inhibin B are specific biomarkersHigh AMH, Inhibin B levels in the prepubertal period is via FSH stimulation, which is mistakenly considered to be silent due to its reduced activity Aim & Objectives: To assess AMH and Inhibin B measurements in the diagnostic workup of prepubertal children with different subtypes of 46,XY DSD and comparing with normal controls To assess Sertoli cell function with AMH and Inhibin B and to assess correlation between testosterone elevation after hCG stimulation, basal AMH and Inhibin B Patients and methods: Pilot study-Single centered, Cross-sectional Observational study. After ethical committee approval, 40 children with 46,XY DSD & 40 healthy age matched, boys as controls recruited after taking assent. All children with DSD underwent karyotyping, assessment of hCG stimulated testosterone, DHT and androstenedione. Basal AMH and inhibin B were measured in both cases and controls. Data were analysed using IBM SPSS version 25. Results: The mean age at presentation was 4.09 years.The diagnosis was made clinically and biochemically, genetic analysis done in few patients. Out of 40 cases, 26 had normal hCG stimulated testosterone of >100 ng/dl (17 cases were 5 alpha reductase type 2 deficiency [5αR2D], 9 cases were PAIS) & 14 had low hCG stimulated testosterone of <100 ng/dl (8 cases were 17βHSD3 deficiency, 4 cases were Partial gonadal dysgenesis [PGD], 2 cases were Vanishing testis syndrome). In the low testosterone group, mean AMH in 17βHSD3 deficiency-279.95 ng/ml, in PGD-31.16 ng/ml which is statistically significant in differentiating these disorders(p-0.002)& mean Inhibin B in 17βHSD3 deficiency-186.41 pg/ml, in PGD-35.95 pg/ml which is statistically significant in differentiating these disorders (p-0.007). In vanishing testis syndrome, AMH & Inhibin B were helpful in confirming the absent functioning testicular tissue Whereas in normal testosterone group, mean AMH in PAIS-235.65 ng/ml, in 5αR2D-289.08 ng/ml difference is not statistically significant(p-0.36)& mean Inhibin B in PAIS-204.50 pg/ml, in 5αR2D-190.91 pg/ml difference is not statistically significant(p-0.72) There was significant correlation between basal AMH and hCG stimulated testosterone (r=0.434; p-0.002), Inhibin B and hCG stimulated testosterone(r=0.438; p-0.001), AMH and Inhibin B(r=0.770; p<0.001). Conclusion: AMH and Inhibin B are valuable in differentiating PGD, 17βHSD3 deficiency in low hCG stimulated testosterone patients, but not helpful in differentiating PAIS, 5αR2D in normal hCG stimulated testosterone patients. Especially in PGD they may have a role with respect to fertility prospects and malignancy risk assessment. Presentation: 6/3/2024

Transcriptome profiling of barnyard millet (Echinochloa frumentacea L.) during grain development to reveal the genomic insights into iron accumulation

In the realm of food nutritional security, the development of mineral-rich grains assumes a pivotal role in combating malnutrition. Within the scope of the current investigation, we endeavoured to discern the transcripts accountable for the improved accumulation of grain-Fe within Indian barnyard millet. This pursuit entailed transcriptome sequencing of genotypes BAR-1433 (with high Fe content) and BAR-1423 (with low Fe content) during two distinct stages of spike development—spike emergence and milking stage. In the context of spike emergence, we identified a cohort of 895 up-regulated transcripts and 126 down-regulated transcripts that delineated the difference between the high and low grain-Fe genotypes. In contrast, during the milking stage, the tally of up-regulated transcripts reached 436, while down-regulated transcripts numbered 285. The transcripts that consistently ascended in both developmental stages underwent functional annotation, aligning their roles with nucleolar proteins, metal-nicotianamine transporters, ribonucleoprotein complexes, vinorine synthases, cellulose synthases, auxin response factors, embryogenesis abundant proteins, cytochrome c oxidases, and zinc finger BED domain-containing proteins. Meanwhile, a heterogeneous spectrum of transcripts exhibited differential expression and upregulation throughout the distinct stages. These transcripts encompassed various facets, such as ABC Transporter family proteins, Calcium-dependent kinase family, Ferritin, Metal ion binding, Iron-sulfur cluster binding, Cytochrome family, Zinc finger transcription factor family, Ferredoxin–NADP reductase type 1 family, Putative laccase, Multicopper oxidase family, and Terpene synthase family. To authenticate the reliability of these transcripts, six contigs representing probable functions, including metal transporters, iron sulfur coordination, metal ion binding, auxin-responsive GH3-like protein 2, and cytochrome P450 71B16, were harnessed for primer design. Subsequently, these primers were utilized in the validation process through qRT-PCR, with the outcomes aligning harmoniously with the transcriptome results. This study chronicles a constellation of genes linked to elevated iron content within barnyard millet, showcasing a proof of concept for leveraging transcriptome insights in marker-assisted selection to fortify barnyard millet with iron. This marks the inaugural comprehensive transcriptome analysis delineating transcripts associated with varying levels of grain-iron content during the panicle developmental stages within the barnyard millet paradigm.

The DmsABC S-oxide reductase is an essential component of a novel, hypochlorite-inducible system of extracellular stress defense in Haemophilus influenzae.

Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted pathogen, Haemophilus influenzae. In several different infection models, H. influenzae ΔdmsA strains showed reduced immunogenicity as well as lower levels of survival in contact with host cells. Expression of DmsABC was induced in the presence of hypochlorite and paraquat, closely linking this enzyme to defense against host-produced antimicrobials. In addition to methionine sulfoxide, DmsABC converted nicotinamide- and pyrimidine-N-oxide, precursors of NAD and pyrimidine for which H. influenzae is an auxotroph, at physiologically relevant concentrations, suggesting that these compounds could be natural substrates for DmsABC. Our data show that DmsABC forms part of a novel, periplasmic system for defense against host-induced S- and N-oxide stress that also comprises the functionally related MtsZ S-oxide reductase and the MsrAB peptide methionine sulfoxide reductase. All three enzymes are induced following exposure of the bacteria to hypochlorite. MsrAB is required for physical resistance to HOCl and protein repair. In contrast, DmsABC was required for intracellular colonization of host cells and, together with MtsZ, contributed to resistance to N-Chlorotaurine. Our work expands and redefines the physiological role of DmsABC and highlights the importance of different types of S-oxide reductases for bacterial virulence.

The Candida albicans ζ-crystallin homolog Zta1 promotes resistance to oxidative stress.

Candida albicans is an important human pathogen that can cause lethal systemic infections. The ability of C. albicans to colonize and establish infections is closely tied to its highly adaptable nature and capacity to resist various types of stress, including oxidative stress. Previous studies showed that four C. albicans proteins belonging to the flavodoxin-like protein family of quinone reductases are needed for resistance to quinones and virulence. Therefore, in this study, we examined the role of a distinct type of quinone reductase, Zta1, and found that it acts in conjunction with the flavodoxin-like proteins to protect against oxidative stress.

Genetic and other epidemiological risk factors of infants and children with hypospadias: a case control study

BackgroundTo study hypospadias as regard epidemiological risk factors and genetic association with mutations in Steroid 5 alpha reductase type 2 genes.MaterialsThis study was conducted on two groups; the first group included 50 male children with hypospadias and the other group included 50 male healthy children as a matched control. All patients and controls were subjected to detailed history, physical examination and molecular study of 5-alpha-reductase gene polymorphisms (V89L and G34R).ResultsMean age in hypospadias group was 3.28 ± 2.87 years. The most common type of hypospadias was the glanular type in 19 children (38%). Higher maternal and paternal age, consanguinity, rural residence and preterm labor carry significant epidemiological risk factors for hypospadias. According to genetic study, all healthy children carried the wild valine residue (VV) genotype, while only 44% of hypospadias cases carried the wild VV genotype and 56% carried the mutant L allele (homozygote for leucine residue and heterozygote for both valine and leucine (VL)) with high significant p value (p < 0.001). For Allele Specific—polymerase chain reaction for glycine to arginine (G34R) mutation detection in the 5 alpha reductase type 2 gene, hypospadias children had significantly higher frequency of heterozygous GR genotype than healthy controls. Binary logistic regression analysis showed that mother age and rural residence were the most independent predictors for hypospadias.ConclusionsV89L and G34R Steroid 5 alpha reductase type 2 gene polymorphisms, higher maternal and paternal age, consanguinity, rural residence and preterm labor carry significant risk factors for hypospadias. On multivariate logistic regression, mother age and rural residence are the most independent predictors for hypospadias.

Labour and premature delivery differentially affect the expression of the endocannabinoid system in the human placenta

Plasma concentrations of N-arachidonyletholamine (AEA), N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA) increase at term and can predict when a woman is likely to go into labour. We hypothesised that increased plasma AEA concentrations in women in preterm and term labour might also be increased and have a function in the placenta at the end of pregnancy. Here we examined the expression of the N-acylethanolamine-modulating enzymes fatty acid amide hydrolase (FAAH) and N-acyl-phosphatidylethanolamine-specific phospholipase-D (NAPE-PLD) and of the cannabinoid receptors (CB1 and CB2) in the placenta and their activation in an in vitro model of the third-trimester placenta to determine if those expressions change with labour and have functional significance. Expression of CB1, CB2, FAAH and NAPE-PLD was examined by immunohistochemistry (IHC) and RT-qPCR in placental samples obtained from four patient groups: preterm not in labour (PTNL), term not in labour (TNL), preterm in labour (PTL) and term in labour (TL). Additionally, the effects of AEA on a third-trimester human cell line (TCL-1) were evaluated. All ECS components were present in the third-trimester placenta, with NAPE-PLD and CB2 being the key modulated proteins in terms of expression. Functionally, AEA reduced TCL-1 cell numbers through the actions of the CB2 receptor whilst CB1 maintained placental integrity through the expression of the transcription regulators histone deacetylase 3, thyroid hormone receptor β 1 and the modulation of 5α reductase type 1. The placenta in the third trimester and at term is different from the placenta in the first trimester with respect to the expression of CB1, CB2, FAAH and NAPE-PLD, and the expression of these proteins is affected by labour. These data suggest that early perturbation of some ECS components in the placenta may cause AEA-induced PTL and thus PTB.

Two New Components from an Association of Marine Sponges Poecillastra sp. and Jaspis sp. and Their Inhibitory Effects on Biomarkers for Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH), characterized by the enlargement of the prostate gland and subsequent lower urinary tract symptoms, poses a significant health concern for aging men with increasing prevalence. Extensive efforts encompassing in vitro and in vivo models are underway to identify novel and effective agents for the management and treatment of BPH. Research endeavors are primarily channeled toward assessing the potential of compounds to inhibit cell proliferation, curb inflammation, and display anti-androgenic activity. Notably, through screening aimed at inhibiting 5-alpha reductase type 2 (5αR2) in human prostatic cells, two acyl compounds (1 and 2) were isolated from a bioactive fraction sourced from an association of marine sponges Poecillastra sp. and Jaspis sp. The complete structure of 1 was determined as (Z)-dec-3-enony (2S, 3S)-capreomycidine, ascertained by JBCA and ECD comparison. While the absolute configurations of 2 remained unassigned, it was identified as a linkage of a 2, 7S*-dihydoxy-9R*-methyloctadecanoyl group with the 2-amino position of a tramiprosate moiety referred to as homotaurine. Evaluation of both compounds encompassed the assessment of their inhibitory effects on key biomarkers (5αR2, AR, PSA, and PCNA) associated with BPH in testosterone propionate (TP)-activated LNCap and RWPE-1 cells.

Identification and characterization of archaeal and bacterial F420 -dependent thioredoxin reductases.

The thioredoxin pathway is an antioxidant system present in most organisms. Electrons flow from a thioredoxin reductase to thioredoxin at the expense of a specific electron donor. Most known thioredoxin reductases rely on NADPH as a reducing cofactor. Yet, in 2016, a new type of thioredoxin reductase was discovered in Archaea which utilize instead a reduced deazaflavin cofactor (F420 H2 ). For this reason, the respective enzyme was named deazaflavin-dependent flavin-containing thioredoxin reductase (DFTR). To have a broader understanding of the biochemistry of DFTRs, we identified and characterized two other archaeal representatives. A detailed kinetic study, which included pre-steady state kinetic analyses, revealed that these two DFTRs are highly specific for F420 H2 while displaying marginal activity with NADPH. Nevertheless, they share mechanistic features with the canonical thioredoxin reductases that are dependent on NADPH (NTRs). A detailed structural analysis led to the identification of two key residues that tune cofactor specificity of DFTRs. This allowed us to propose a DFTR-specific sequence motif that enabled for the first time the identification and experimental characterization of a bacterial DFTR.

MP24-06 TNF-ALPHA INHIBITOR THERAPY SUPPRESSES GROWTH OF THE PROSTATE GLAND

You have accessJournal of UrologyCME1 Apr 2023MP24-06 TNF-ALPHA INHIBITOR THERAPY SUPPRESSES GROWTH OF THE PROSTATE GLAND Ra'ad Al-Faouri, Christina Sharkey, Leo L. Tsai, Zongwei Wang, and Aria F. Olumi Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Christina SharkeyChristina Sharkey More articles by this author , Leo L. TsaiLeo L. Tsai More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003249.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have established a relationship between prostate inflammation and the development of BPH. Steroid 5 alpha reductase type 2 (SRD5A2) is a pivotal enzyme in the development and growth of the prostate gland and the critical target for BPH therapy. We previously demonstrated that tumor necrosis factor alpha (TNF-a) regulates the epigenetic change of SRD5A2, leading to suppression of SRD5A2 gene and protein expression. However, little is known whether TNF-a inhibitor therapy affects prostatic growth. Here we aimed to evaluate the effect of TNF-a inhibitor therapy on the growth rate of prostate through analyzing the data of serial pelvic imaging scans. METHODS: In this retrospective cohort study, electronic records at Beth Israel Deaconess Medical Center were searched for men aged 18 and over who had serial pelvic Images (MRI or CT scans) while receiving TNF-a inhibitors. 99 men were included in the treatment cohort after applying exclusion criteria (TNF-a treatment duration <1 year, any pelvic/prostate surgery/radiation, use of 5ARIs, advanced prostate cancer, androgen deprivation therapy, testosterone therapy, poor image quality, or imaging interval <1 year). An age-matched cohort was constructed with the same inclusion/exclusion criteria but absent TNF-a therapy (n=99). The total prostate volume (TPV) was measured and calculated from baseline and follow-up imaging. Clinical data was collected for all men. RESULTS: There were no significant differences between the two groups in age, demographics, BMI or comorbidities. Mean baseline TPV was similar in the TNF-a inhibitor therapy group and control group (27.52±8.9 cc vs 27.3±9.6 cc, p-value: 0.71). For the entire cohort, the average imaging follow up duration was 3.79±0.32 years with no significant difference between the treatment and control groups. The median growth rate for men in the treatment cohort was significantly lower than those in the control group (-0.01 cc/year IQR= 1.2 compared to 0.68 cc/year IQR= 2.8, P-value 0.001). In a multiple regression model adjusting for age, race, initial TPV and BMI, men in the treatment group still had a significantly lower growth rate compared to the control group (-0.03 cc/year IQR: 0.82 vs 0.67 cc/year IQR: 0.93, p-value: 0.001). CONCLUSIONS: TNF-a inhibitors are negatively correlated with prostatic growth. Men with autoimmune diseases who are treated with TNF-a inhibitors may experience fewer urinary symptoms related to prostatic enlargement. Our study suggests that inflammatory mediators regulate prostatic growth. Source of Funding: NIH: R01DK124502 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e319 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ra'ad Al-Faouri More articles by this author Christina Sharkey More articles by this author Leo L. Tsai More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF downloadLoading ...

Effect of tillage state of paddy soils with heavy metal pollution on the nosZ gene of N2O reductase

Paddy soils are an important source of atmospheric nitrous oxide (N2O). However, numerous studies have focused on N2O production during the soil tillage period, neglecting the N2O production during the dry fallow period. In this study, we conducted an incubation experiment using the acetylene inhibition technique to investigate N2O emission and reduction rates of paddy soil profiles (0-1 m) from Guangdong Province and Jinlin Province in China, with different heavy-metal pollution levels. The abundance and community structures of denitrifying bacteria were determined via quantitative-PCR and Illumina MiSeq sequencing of nosZ, nirK, and nirS genes. Our results showed that the potential N2O emission rate, N2O production rate, and denitrification rate have decreased with increasing soil vertical depth and heavy-metal pollution. More importantly, we found that the functional gene type of N2O reductase switched with the tillage state of paddy soils, which clade Ⅱ nosZ genes were the dominant gene during the tillage period, while clade Ⅰ nosZ genes were the dominant gene during the dry fallow period. The heavy-metal pollution has less effect on the niche differentiation of the nosZ gene. The N2O emission rate was significantly regulated by the genus Bradyhizobium, which contains both N2O reductase and nitrite reductase genes. Our findings suggests that the nosZ gene of N2O reductase can significantly impact the N2O emission from paddy soils.

A chromosome-level genome assembly reveals that a bipartite gene cluster formed via an inverted duplication controls monoterpenoid biosynthesis in Schizonepeta tenuifolia

Biosynthetic gene clusters (BGCs) are regions of a genome where genes involved in a biosynthetic pathway are in proximity. The origin and evolution of plant BGCs as well as their role in specialized metabolism remain largely unclear. In this study, we have assembled a chromosome-scale genome of Japanese catnip (Schizonepeta tenuifolia) and discovered a BGC that contains multiple copies of genes involved in four adjacent steps in the biosynthesis of p-menthane monoterpenoids. This BGC has an unprecedented bipartite structure, with mirrored biosynthetic regions separated by 260 kilobases. This bipartite BGC includes identical copies of a gene encoding an old yellow enzyme, a type of flavin-dependent reductase. In vitro assays and virus-induced gene silencing revealed that this gene encodes the missing isopiperitenone reductase. This enzyme evolved from a completely different enzyme family to isopiperitenone reductase from closely related Mentha spp., indicating convergent evolution of this pathway step. Phylogenomic analysis revealed that this bipartite BGC has emerged uniquely in the S. tenuifolia lineage and through insertion of pathway genes into a region rich in monoterpene synthases. The cluster gained its bipartite structure via an inverted duplication. The discovered bipartite BGC for p-menthane biosynthesis in S. tenuifolia has similarities to the recently described duplicated p-menthane biosynthesis gene pairs in the Mentha longifolia genome, providing an example of the convergent evolution of gene order. This work expands our understanding of plant BGCs with respect to both form and evolution, and highlights the power of BGCs for gene discovery in plant biosynthetic pathways.

Upregulation of mir-1199-5p is associated with reduced type 2 5-α reductase expression in benign prostatic hyperplasia

Background5-α reductase inhibitors (5-ARIs) are first-line drugs for managing benign prostatic hyperplasia (BPH). Unfortunately, some patients do not respond to 5-ARI therapy and may even show worsening symptoms. The decreased expression of steroid 5-α reductase type 2(SRD5A2) in BPH tissues may explain the failure of 5-ARI therapy, however, the mechanisms underlying SRD5A2 decreased remained unelucidated.ObjectivesTo investigate microRNA-mediated regulation of the expression of SRD5A2 resulting in 5-ARI therapy failure.Materials and methodsThe expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR. Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry.ResultsSRD5A2 expression was variable; it was negative, weak, and strong in 13.6%, 28.8%, and 57.6% of BPH tissues respectively. The normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression was remarkably higher in BPH-1 than in RWPE-1 cells(P<0.001), and miR-1199-5p expression was significantly upregulated in BPH tissues with negative SRD5A2 expression than those with positive SRD5A2 expression. Transfection of miR-1199-5p mimics in RWPE-1 cells led to a marked decrease in SRD5A2 expression, whereas miR-1199-5p inhibitor increased SRD5A2 expression in BPH-1 cells. Dual-luciferase reporter assay showed that miR-1199-5p could bind the 3′untranslated region of SRD5A2 mRNA. miR-1199-5p also decreased the RWPE-1 sensibility to finasteride, an inhibitor of SRD5A2.ConclusionOur results show that SRD5A2 expression varies in BPH tissues and miR-1199-5p might be one of the several factors contributing to differential SRD5A2 expression in BPH patients.

Camellia Seed Cake Extract Supports Hair Growth by Abrogating the Effect of Dihydrotestosterone in Cultured Human Dermal Papilla Cells.

Autocrine and paracrine factors play key roles in the process of Androgenetic alopecia (AGA), which are secreted by balding dermal papilla cells (DPCs) after dihydrotestosterone (DHT) induction. Camellia seed cake is an oriental oil extraction byproduct, and its extract has been traditionally used to wash hair in China. This study elucidated the hair growth-promoting effects of Camellia seed cake extract (CSCE) in DHT-treated cultured DPCs and its underlying mechanisms. The effect of CSCE on cell viability and release of inflammatory factors IL-6 and IL-1α was performed on human dermal papilla cells (DPCs) incubated with DHT. Relative expression of bax, bcl-2, p53, androgen receptor (AR) and 5α- reductase type II (SRD5A2) was determined by PCR. Senescence-associated was examined by β-galactosidase (SA-β-Gal) assays. CSCE restored DHT-induced cell damage in a dose-dependent manner, and effectively reduced the production of IL-6 and IL-1α in DHT-treated DPCs. CSCE exhibited an anti-apoptotic effect, which increased the expression of bcl-2, and decreased the expressions of bax and p53 in DHT-incubated DPCs. CSCE also showed an anti-androgenic effect reversing the increase in AR and SRD5A2 expressions in DPCs driven by DHT incubation. In addition, CSCE inhibited the β-galactosidase enzyme activity and slowed down the cell senescence of DPCs which is crucial for AGA progression. In this study, we found that CSCE may have the potential to prevent and alleviate AGA by abrogating the effect of DHT in cultured DPCs.

Nitric Oxide, Nitric Oxide Formers and Their Physiological Impacts in Bacteria.

Nitric oxide (NO) is an active and critical nitrogen oxide in the microbe-driven nitrogen biogeochemical cycle, and is of great interest to medicine and the biological sciences. As a gas molecule prior to oxygen, NO respiration represents an early form of energy generation via various reactions in prokaryotes. Major enzymes for endogenous NO formation known to date include two types of nitrite reductases in denitrification, hydroxylamine oxidoreductase in ammonia oxidation, and NO synthases (NOSs). While the former two play critical roles in shaping electron transport pathways in bacteria, NOSs are intracellular enzymes catalyzing metabolism of certain amino acids and have been extensively studied in mammals. NO interacts with numerous cellular targets, most of which are redox-active proteins. Doing so, NO plays harmful and beneficial roles by affecting diverse biological processes within bacterial physiology. Here, we discuss recent advances in the field, including NO-forming enzymes, the molecular mechanisms by which these enzymes function, physiological roles of bacterial NOSs, and regulation of NO homeostasis in bacteria.

Methionine sulfoxide reductase B5 plays a key role in preserving seed vigor and longevity in rice (Oryza sativa).

Oxidation of methionine leads to the formation of methionine S-sulfoxide and methionine R-sulfoxide, which can be reverted by two types of methionine sulfoxide reductase (MSR): MSRA and MSRB. Though the role of MSR enzymes has been elucidated in various physiological processes, the regulation and role of MSR in seeds remains poorly understood. In this study, through molecular, biochemical, and genetic studies using seed-specific overexpression and RNAi lines of OsMSRB5 in Oryza sativa, we demonstrate the role of OsMSRB5 in maintaining seed vigor and longevity. We show that an age-induced reduction in the vigor and viability of seeds is correlated with reduced MSR activity and increased methionine sulfoxide (MetSO) formation. OsMSRB5 expression increases during seed maturation and is predominantly localized to the embryo. Further analyses on transgenic lines reveal the role of OsMSRB5 in modulating reactive oxygen species (ROS) homeostasis to preserve seed vigor and longevity. We show that ascorbate peroxidase and PROTEIN l-ISOASPARTYL METHYLTRANSFERASE undergo MetSO modification in seeds that affects their functional competence. OsMSRB5 physically interacts with these proteins and reverts this modification to facilitate their functions and preserve seed vigor and longevity. Our results thus illustrate the role of OsMSRB5 in preserving seed vigor and longevity by modulating ROS homeostasis in seeds.

Chromium, its properties, transformation, and impact on humans

This review presents current views on the features of сhromium and its compounds, their interconversion, reduction of Cr (VI) by microorganisms, as well as the impact of chromium (VI) on the environment and humans. Chromium can have positive and negative effects on health, according to the dose, exposure time, and oxidation state. The most common forms of this metal in biological systems are trivalent Cr(III) and hexavalent Cr(VI). Hexavalent chromium is mobile, highly toxic to humans, and animals and considered a priority environmental pollutant. He is highly soluble and mobile. On the contrary, Cr(III) has relatively low toxicity and mobility and it is one of the micronutrients needed by humans. Сhromium (III) is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins, and fats. Considerable attention is paid to the issues of interconversion of chromium compounds, reduction of Cr (VI) to Cr (III) by microorganisms, as well as physiological features of their action in humans. The present review discusses on the types of chromate reductases found in different bacteria, their mode of action, and potential applications in the bioremediation of hexavalent chromium. Іn the human body chromium (VI) is rapidly reduced to chromium (III) after penetration of biological membranes and in the gastric environment. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with stress oxidative tissue damage and a cascade of cellular events, contribute to the cytotoxicity, genotoxicity, and carcinogenicity of Cr(VI)-containing compounds.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway.

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

Computational Development of Inhibitors of Plasmid-Borne Bacterial Dihydrofolate Reductase.

Resistance to trimethoprim and other antibiotics targeting dihydrofolate reductase may arise in bacteria harboring an atypical, plasmid-encoded, homotetrameric dihydrofolate reductase, called R67 DHFR. Although developing inhibitors to this enzyme may be expected to be promising drugs to fight trimethoprim-resistant strains, there is a paucity of reports describing the development of such molecules. In this manuscript, we describe the design of promising lead compounds to target R67 DHFR. Density-functional calculations were first used to identify the modifications of the pterin core that yielded derivatives likely to bind the enzyme and not susceptible to being acted upon by it. These unreactive molecules were then docked to the active site, and the stability of the docking poses of the best candidates was analyzed through triplicate molecular dynamics simulations, and compared to the binding stability of the enzyme–substrate complex. Molecule 32 ([6-(methoxymethyl)-4-oxo-3,7-dihydro-4H-pyrano[2,3-d]pyrimidin-2-yl]methyl-guanidinium) was shown by this methodology to afford extremely stable binding towards R67 DHFR and to prevent simultaneous binding to the substrate. Additional docking and molecular dynamics simulations further showed that this candidate also binds strongly to the canonical prokaryotic dihydrofolate reductase and to human DHFR, and is therefore likely to be useful to the development of chemotherapeutic agents and of dual-acting antibiotics that target the two types of bacterial dihydrofolate reductase.

Complete genome sequence of marine photoheterotophic bacterium Erythrobacter sp. JK5.

Erythrobacter sp. JK5, a marine heterotrophic bacterium, was isolated from marine sediment in Jeju island, the Republic of Korea. Here, we report information on the complete genome of strain JK5, including a putative capability for photosynthesis. The genome of JK5 consisted of 3.34 Mbp with 64.2% G+C content, and contained 3210 protein-coding sequences and three rRNA genes. Genomic analysis revealed that strain JK5 might be grown under oxic, microoxic, or anoxic conditions using two types of terminal oxidase (high and low oxygen affinity) or nitrate reductase. The types IV and VI secretion systems presented in strain JK5 genome might reveal a survival advantage against their ecological competitors in the marine environment.