Modification Of Macromolecules Research Articles

The Detection Methods of Hydroxyl Radical: A Review

Hydroxyl radical (·OH) can rapidly react with biological macromolecules, organic and inorganic substances on account of its strong oxidizing property, so it is widely used in sewage treatment, chemiluminescence analysis, biological macromolecule modification and other fields. The strengthening effect of Hydrodynamic cavitation on chemical reactions depends on the number of free radicals initiated by cavitation. These free radicals are highly reactive and react rapidly with pollutants and other species in wastewater. Therefore, the systematic summary of detection methods of hydroxyl radical and the description of its advantages and disadvantages can provide technical support for scientific researchers, and guides the research in the future.

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases.

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Accessing the Thiol Toolbox: Synthesis and Structure-Activity Studies on Fluoro-Thiol Conjugated Antimicrobial Peptides.

The para-fluoro-thiol reaction (PFTR) is a modern name for the much older concept of a nucleophilic aromatic substitution reaction in which the para-position fluorine of a perfluorinated benzene moiety is substituted by a thiol. As a rapid and mild reaction, the PFTR is a useful technique for the post-synthetic modification of macromolecules like peptides on the solid phase. This reaction is of great potential since it allows for peptide chemists to access the vast catalogue of commercially available thiols with diverse structures to conjugate to peptides, which may impart favorable biological activity, particularly in antimicrobial sequences. This work covers the generation of a library of antimicrobial peptides by modifying a relatively inactive tetrapeptide with thiols of various structures using the PFTR to grant antimicrobial potency to the core sequence. In general, nucleophilic substitution of the peptide scaffold by hydrophobic thiols like cyclohexanethiol and octanethiol imparted the greatest antimicrobial activity over that of hydrophilic thiols bearing carboxylic acid or sugar moieties, which were ineffectual at improving the antimicrobial activity. The general trend here follows expected structure-activity relationship outcomes like that of changing the acyl group of lipopeptide antibiotics and is encouraging for the use of this reaction for structural modifications of antimicrobial sequences further.

Analysis of the level of oxidative stress by assessing the damage to the plasma protein serum albumin under the influence of an oxidizing agent

Oxidative stress, which leads to oxidative modification of various macromolecules, including proteins, is now considered an important pathogenetic link in many diseases. In this work, oxidative damage to a blood plasma protein, bovine serum albumin BSA, under the action of an oxidizing agent, hydrogen peroxide H2O2, was studied by spectrofluorometric method. The H2O2 concentration-dependent quenching of the intrinsic fluorescence of BSA is shown. BSA fluorescence quenching constants in hydrogen peroxide solutions are calculated by mathematical modeling methods. The dependences found in the fluorescence quenching constants are explained both by oxidative damage to the microenvironment of BSA tryptophan residues and by changes in the native conformation of protein globules upon oxidative damage. More significant peroxide damage to BSA occurs at lower pH values due to the fact that H2O2, as an oxidizing agent, acts more strongly in an acidic environment. The registered quenching of the protein's own fluorescence when damaged by an oxidizing agent can be used as a medical method for assessing the level of oxidative stress in the body in the diagnosis of a number of diseases.

The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer.

Background and Objectives: Mounting evidence implicates oxidative damage in prostate carcinogenesis, contributing to modifications of macromolecules that drive cellular malignant transformation. Functional single-nucleotide polymorphisms (SNPs) of enzymes involved in redox homeostasis can disrupt pro-oxidant–antioxidant balance, leading to accumulation of reactive oxygen species and oxidative damage. We investigated the potential role of genetic polymorphisms of antioxidant enzymes glutathione peroxidase 1 (GPX1 rs1050450) and superoxide dismutase 2 (SOD2 rs4880) and regulatory antioxidant protein nuclear factor erythroid 2-related factor 2 (Nrf2 rs6721961) in the susceptibility to prostate cancer development (PC) and prognosis. Materials and Methods: We conducted a case–control study consisting of 235 patients with PC and 240 controls. Gene polymorphisms were determined by quantitative polymerase chain reaction (qPCR) and polymerase chain reaction with confronting two-pair primers (PCR-CTTP) methods. Multiple risk models were composed to inspect the separate and mutual effect of multiple genes and in combination with acquired contributory factors on the risk of PC development. Results: Independently, carriers of at least one SOD2*C allele had increased risk of PC development, which was significantly further amplified in advanced statistical models. When tested in combination, individuals with both SOD2*C allele and Nrf2*C/C genotype were also at increased risk of PC development, which was augmented when combined with acquired contributory factors. During the mean 75 ± 25 months of follow-up, investigated gene polymorphisms did not affect overall survival. Conclusion: Our results suggest that these gene polymorphisms could be used as risk biomarkers of PC evolution.

New insights into the role of the Golgi apparatus in the pathogenesis and therapeutics of human diseases.

The Golgi apparatus is an essential cellular organelle that mediates homeostatic functions, including vesicle trafficking and the post-translational modification of macromolecules. Its unique stacked structure and dynamic functions are tightly regulated, and several Golgi proteins play key roles in the functioning of unconventional protein secretory pathways triggered by cellular stress responses. Recently, an increasing number of studies have implicated defects in Golgi functioning in human diseases such as cancer, neurodegenerative, and immunological disorders. Understanding the extraordinary characteristics of Golgi proteins is important for elucidating its associated intracellular signaling mechanisms and has important ramifications for human health. Therefore, analyzing the mechanisms by which the Golgi participates in disease pathogenesis may be useful for developing novel therapeutic strategies. This review articulates the structural features and abnormalities of the Golgi apparatus reported in various diseases and the suspected mechanisms underlying the Golgi-associated pathologies. Furthermore, we review the potential therapeutic strategies based on Golgi function.

Dendronized Gelatin-Mediated Synthesis of Gold Nanoparticles

Thermoresponsive dendronized gelatins (GelG1) or gelatin methacrylates (GelG1MA) were used as precursors to modulate the efficient reduction of Au(III) to form stable gold nanoparticles (AuNPs) through UV irradiation. These dendronized gelatins were obtained through the amidation of gelatin or gelatin methacrylates with dendritic oligoethylene glycols (OEGs). Crowded OEG dendrons along the gelatin backbones create a hydrophobic microenvironment, which promotes the reduction of Au(III). Gelatin backbones act as ligands through the electron-rich groups to facilitate the reduction, while the dendritic OEGs provide shielding effects through crowding to form a hydrophobic microenvironment, which not only enhances the reduction but also stabilize the formed AuNPs through encapsulation. The effects of dendron coverage on the dendronized biomacromolecules and their thermoresponsiveness on the reduction kinetics were examined. Dendronized gelatin/AuNPs hydrogels were further prepared through the in situ photo-crosslinking of GelG1MA. The modification of natural macromolecules through dendronization presented in this report facilitates a novel platform for the environmentally friendly synthesis of noble metal nanoparticles, which may form a new strategy for developing smart nano-biosensors and nano-devices.

Integrated Fertilization with Bagasse Vermicompost Changes the Microbiome of Mencía Must and Wine

Winemaking is a well-known process that includes several steps in the production of grape must and wine. Grape marc, or bagasse, is a byproduct of wine production that can be vermicomposted and used as organic fertilizer. Grape marc vermicompost has microbial communities that are richer and more stable than grape marc alone, and its addition to a vineyard’s terroir can improve grape yields and wine quality. Here we compare the must and wine microbiota of Mencía from grapevines treated with and without (standard fertilization) vermicompost derived from Mencía grape marc. Mencía is a high-quality red wine broadly grown in Galicia, Spain, and is appreciated for its fresh acidity and fruity flavors. When Mencía grapevines are treated with vermicompost derived from its grape marc, Mencía vines increase their grape production, and the final wine improves its organoleptic properties. Metataxonomic analyses of the bacterial 16S rRNA and fungal ITS gene regions showed that Mencía must and wine have the distinct taxonomic composition (phyla, genera and ASVs—amplicon sequence variants) of bacterial and fungal groups. Must and wine bacteriotas and mycobiotas show no significant variation in alpha-diversity, while wine bacteriotas and mycobiotas show significant differences in microbial structure (beta-diversity) between treated and control grapevines. Likewise, the functional diversity and predicted metabolic pathways (biosynthesis, degradation/utilization/assimilation, generation of precursor metabolites and energy, macromolecule modification and superpathways) of the must and wine microbiota also show significant changes. Our study proposes that changes in the abundance of microbial taxa and the metabolic processes they undergo during winemaking may improve Mencía’s organoleptic properties and productivity.

Network Biology Approaches to Uncover Therapeutic Targets Associated with Molecular Signaling Pathways from circRNA in Postoperative Cognitive Dysfunction Pathogenesis.

Postoperative cognitive dysfunction (POCD) is a cognitive deterioration and dementia that arise after a surgical procedure, affecting up to 40% of surgery patients over the age of 60. The precise etiology and molecular mechanisms underlying POCD remain uncovered. These reasons led us to employ integrative bioinformatics and machine learning methodologies to identify several biological signaling pathways involved and molecular signatures to better understand the pathophysiology of POCD. A total of 223 differentially expressed genes (DEGs) comprising 156 upregulated and 67 downregulated genes were identified from the circRNA microarray dataset by comparing POCD and non-POCD samples. Gene ontology (GO) analyses of DEGs were significantly involved in neurogenesis, autophagy regulation, translation in the postsynapse, modulating synaptic transmission, regulation of the cellular catabolic process, macromolecule modification, and chromatin remodeling. Pathway enrichment analysis indicated some key molecular pathways, including mTOR signaling pathway, AKT phosphorylation of cytosolic targets, MAPK and NF-κB signaling pathway, PI3K/AKT signaling pathway, nitric oxide signaling pathway, chaperones that modulate interferon signaling pathway, apoptosis signaling pathway, VEGF signaling pathway, cellular senescence, RANKL/RARK signaling pathway, and AGE/RAGE pathway. Furthermore, seven hub genes were identified from the PPI network and also determined transcription factors and protein kinases. Finally, we identified a new predictive drug for the treatment of SCZ using the LINCS L1000, GCP, and P100 databases. Together, our results bring a new era of the pathogenesis of a deeper understanding of POCD, identified novel therapeutic targets, and predicted drug inhibitors in POCD.

OGG1 in Lung-More than Base Excision Repair.

As the organ executing gas exchange and directly facing the external environment, the lungs are challenged continuously by various stimuli, causing the disequilibration of redox homeostasis and leading to pulmonary diseases. The breakdown of oxidants/antioxidants system happens when the overproduction of free radicals results in an excess over the limitation of cleaning capability, which could lead to the oxidative modification of macromolecules including nucleic acids. The most common type of oxidative base, 8-oxoG, is considered the marker of DNA oxidative damage. The appearance of 8-oxoG could lead to base mismatch and its accumulation might end up as tumorigenesis. The base 8-oxoG was corrected by base excision repair initiated by 8-oxoguanine DNA glycosylase-1 (OGG1), which recognizes 8-oxoG from the genome and excises it from the DNA double strand, generating an AP site for further processing. Aside from its function in DNA damage repairment, it has been reported that OGG1 takes part in the regulation of gene expression, derived from its DNA binding characteristic, and showed impacts on inflammation. Researchers believe that OGG1 could be the potential therapy target for relative disease. This review intends to make an overall summary of the mechanism through which OGG1 regulates gene expression and the role of OGG1 in pulmonary diseases.

ADP-Ribosylation Post-Translational Modification: An Overview with a Focus on RNA Biology and New Pharmacological Perspectives.

Cellular functions are regulated through the gene expression program by the transcription of new messenger RNAs (mRNAs), alternative RNA splicing, and protein synthesis. To this end, the post-translational modifications (PTMs) of proteins add another layer of complexity, creating a continuously fine-tuned regulatory network. ADP-ribosylation (ADPr) is an ancient reversible modification of cellular macromolecules, regulating a multitude of key functional processes as diverse as DNA damage repair (DDR), transcriptional regulation, intracellular transport, immune and stress responses, and cell survival. Additionally, due to the emerging role of ADP-ribosylation in pathological processes, ADP-ribosyltransferases (ARTs), the enzymes involved in ADPr, are attracting growing interest as new drug targets. In this review, an overview of human ARTs and their related biological functions is provided, mainly focusing on the regulation of ADP-ribosyltransferase Diphtheria toxin-like enzymes (ARTD)-dependent RNA functions. Finally, in order to unravel novel gene functional relationships, we propose the analysis of an inventory of human gene clusters, including ARTDs, which share conserved sequences at 3′ untranslated regions (UTRs).

Identification of a Methylation-Regulating Genes Prognostic Signature to Predict the Prognosis and Aid Immunotherapy of Clear Cell Renal Cell Carcinoma.

Methylation is one of the most extensive modifications of biological macromolecules and affects cell-fate determination, development, aging, and cancer. Several methylation modifications, including 5-methylcytosine and N6-methyladenosine, play an essential role in many cancers. However, little is known about the relationship between methylation and the prognosis of clear cell renal cell carcinoma (ccRCC). Here, we established a methylation-regulating genes prognostic signature (MRGPS) to predict the prognoses of ccRCC patients. We obtained ccRCC samples from The Cancer Genome Atlas and identified methylation-regulatingd genes (MRGs) from the Gene Set Enrichment Analysis database. We also determined differentially expressed genes (DEGs) and performed cluster analysis to identify candidate genes. Subsequently, we established and validated an MRGPS to predict the overall survival of ccRCC patients. This was also verified in 15 ccRCC samples collected from the Fujian Provincial Hospital via quantitative real-time transcription (qRT-PCR). While 95 MRGs were differentially expressed (DEGs1) between tumor and normal tissues, 17 MRGs were differentially expressed (DEGs2) between cluster 1 and 2. Notably, 13 genes common among DEGs1 and DEGs2 were identified as hub genes. In fact, we established three genes (NOP2, NSUN6, and TET2) to be an MRGPS based on their multivariate Cox regression analysis coefficients (p < 0.05). A receiver operating characteristic curve analysis confirmed this MRGPS to have a good prognostic performance. Moreover, the MRGPS was associated with characteristics of the tumor immune microenvironment and responses to inhibitor checkpoint inhibitors. Data from “IMvigor 210” demonstrated that patients with a low MRGPS would benefit more from atelozumab (p < 0.05). Furthermore, a multivariate analysis revealed that MRGPS was an independent risk factor associated with ccRCC prognosis (p < 0.05). Notably, a nomogram constructed by combining with clinical characteristics (age, grade, stage, and MRGPS risk score) to predict the overall survival of a ccRCC patient had a favorable predictive value. Eventually, our qRT-PCR results showed that tumor tissues had higher NOP2 and NSUN6 expression levels and lower TET2 expression than normal tissues of ccRCC samples. While the proposed MRGPS comprising NOP2, NSUN6, and TET2 can be an alternative prognostic biomarker for ccRCC patients, it is a promising index for personalized ICI treatments against ccRCC.

From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function.

Sulfotransferases are ubiquitous enzymes that transfer a sulfo group from the universal cofactor donor 3'-phosphoadenosine 5'-phosphosulfate to a broad range of acceptor substrates. In humans, the cytosolic sulfotransferases are involved in the sulfation of endogenous compounds such as steroids, neurotransmitters, hormones, and bile acids as well as xenobiotics including drugs, toxins, and environmental chemicals. The Golgi associated membrane-bound sulfotransferases are involved in post-translational modification of macromolecules from glycosaminoglycans to proteins. The sulfation of small molecules can have profound biologic effects on the functionality of the acceptor, including activation, deactivation, or enhanced metabolism and elimination. Sulfation of macromolecules has been shown to regulate a number of physiologic and pathophysiological pathways by enhancing binding affinity to regulatory proteins or binding partners. Over the last 25 years, crystal structures of these enzymes have provided a wealth of information on the mechanisms of this process and the specificity of these enzymes. This review will focus on the general commonalities of the sulfotransferases, from enzyme structure to catalytic mechanism as well as providing examples into how structural information is being used to either design drugs that inhibit sulfotransferases or to modify the enzymes to improve drug synthesis. SIGNIFICANCE STATEMENT: This manuscript honors Dr. Masahiko Negishi's contribution to the understanding of sulfotransferase mechanism, specificity, and roles in biology by analyzing the crystal structures that have been solved over the last 25 years.

Biosynthesis of Tasikamides via Pathway Coupling and Diazonium-Mediated Hydrazone Formation

Naturally occurring hydrazones are rare despite the ubiquitous usage of synthetic hydrazones in the preparation of organic compounds and functional materials. In this study, we discovered a family of novel microbial metabolites (tasikamides) that share a unique cyclic pentapeptide scaffold. Surprisingly, tasikamides A-C (1-3) contain a hydrazone group (C═N─N) that joins the cyclic peptide scaffold to an alkyl 5-hydroxylanthranilate (AHA) moiety. We discovered that the biosynthesis of 1-3 requires two discrete gene clusters, with one encoding a nonribosomal peptide synthetase (NRPS) pathway for assembling the cyclic peptide scaffold and another encoding the AHA-synthesizing pathway. The AHA gene cluster encodes three ancillary enzymes that catalyze the diazotization of AHA to yield an aryl diazonium species (diazo-AHA). The electrophilic diazo-AHA undergoes nonenzymatic Japp-Klingemann coupling with a β-keto aldehyde-containing cyclic peptide precursor to furnish the hydrazone group and yield 1-3. The studies together unraveled a novel mechanism whereby specialized metabolites are formed by the coupling of two biosynthetic pathways via an unprecedented in vivo Japp-Klingemann reaction. The findings raise the prospect of exploiting the arylamine-diazotizing enzymes (AAD) for the in vivo synthesis of aryl compounds and modification of biological macromolecules.

Dynamic high‐pressure microfluidization enhanced the emulsifying properties of wheat gliadin by rutin

Dynamic high-pressure microfluidization (DHPM) has attracted increasing interest in food macromolecule modification, which has been used in the preparation of nanoemulsions, gel-like soy protein emulsions, and nanocelluloses. This study explored the effects of DHPM under 0, 40, 80, 120, and 160 MPa with the addition of rutin on the physical, structural, rheological, and morphological characteristics of wheat gliadin. Infrared spectrum analysis showed that the DHPM treatment resulted in the structural changes of wheat gliadin and the primary interactions between wheat gliadin and rutin were hydrogen bond and hydrophobic effects. Here, 120 MPa DHPM treatment with the addition of rutin caused decreased particle sizes but increased zeta-potential and viscoelastic properties of wheat gliadin, with particle sizes at 245.20 nm and zeta-potential at 21.76 mV, respectively. The results showed that the combination of DHPM treatment at 120 MPa and rutin to wheat gliadin exhibited the morphology of nanospheres with a more compact structure, uniform particle distribution, and fine emulsifying properties. Practical applications The interaction between protein and polyphenol are able to preserve the stability of the functional compounds, allow targeted and controlled release, improve texture in the food industry. Improvement of functional characteristics of protein-polyphenol complexes with high emulsifying stability during food processing is crucial to use in the food industry. Therefore, the goal of this research is to use a soluble complex of gliadin-rutin for the development of its functional characteristics.

Oxidative homeostasis in follicular fluid and reproductive outcomes - from bench to bedside.

Free radicals and oxidant molecules are part of our organism in a stable balance. However, when addressing female infertility, questions about their role in oocyte quality arise. This review outlines the major alterations of redox homeostasis in the follicular fluid through pathophysiological conditions in female reproduction and its potential effect on IVF outcome. A review of the literature was accurately performed. Manuscripts investigating follicular fluid biomarkers, especially related to oxidant molecules, were screened and used in this review. Studies assessing the follicular reactive species were found and screened. Moreover, studies assessing the IVF outcomes related to biomarkers were considered. The results are provided in an analytical pathway. The study of biomarkers confirms the shift to enhanced oxidizing modification of macromolecules and antioxidative consumption in the follicular fluid of women undergoing IVF treatment. A lack of congruency in methods appears to be marked in the design of scientific studies. However, it is not clear whether redox disbalance has a disruptive effect on the oocyte competence or whether it plays a role in the oocyte maturation process. Red-ox balance plays a questionable role in IVF outcomes. Possible further insights may consider the antioxidant role of adjuvants during controlled ovarian stimulation cycles.

Identification of two downregulated circRNAs in patients with acute B-lymphocytic leukemia.

Acute B-lymphocytic leukemia (B-ALL) is associated with a high mortality rate, with no effective treatment strategies available. The identification of diagnostic and prognostic biomarkers of B-ALL can contribute to the development of novel therapeutic methods and drugs, which can improve the survival outcomes of patients with B-ALL. The present study aimed to identify downregulated circular RNAs (circRNAs) in patients with B-ALL. RNA sequencing was performed to construct the circRNA expression profiles in B-ALL cells and normal human lymphoblasts. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. In addition, reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of the downregulated circRNAs. A total of 263 differentially expressed circRNAs were identified, including 76 upregulated and 187 downregulated circRNAs, respectively. The upregulated circRNAs were mainly enriched in ‘macromolecule modification’, ‘protein modification’ and ‘cellular protein modification processes’, while the downregulated circRNAs were mainly enriched in the ‘negative regulation of RNA biosynthetic processes’, ‘natural killer cell-mediated cytotoxicity’ and ‘viral carcinogenesis’. RT-qPCR analysis demonstrated that two of the downregulated circRNAs (hsa_circ_0000745 and chr15:87949594-87966067-), identified during microarray analysis were also significantly downregulated in Ball-1 cells and B-ALL bone marrow samples. Thus, these circRNAs may serve as biomarkers for patients with B-ALL.

Comparative characterization of microRNAs of Schistosoma japonicum from SCID mice and BALB/c mice: Clues to the regulation of parasite growth and development

Schistosomiasis, caused by a parasite with a wide range of mammalian hosts, remains one of the most prevailing parasitic diseases in the world. While numerous studies have reported that the growth and reproduction of schistosomes in immunodeficient mice was significantly retarded, the underlying molecular mechanisms have yet to be revealed. In this study, we comparatively analyzed the microRNA expression of Schistosoma japonicum derived from SCID and BALB/c mice on the 35th day post-infection by high-throughput RNA sequencing as prominent morphological abnormalities had been observed in schistosomes from SCID mice when compared with those from BALB/c mice. The results revealed that more than 72% and 61% of clean reads in the small RNA libraries of female and male schistosomes, respectively, could be mapped to the selected miRs in the miRBase or the sequences of species-specific genomes. Further analysis identified 122 miRNAs using TPM >0.01 as the threshold value, including 75 known and 47 novel miRNAs, 96 of which were commonly expressed across all the four tested schistosome libraries. Comparative analysis of the libraries of schistosomes from SCID and BALB/c mice identified 15 differentially expressed miRNAs (5 up-regulated and 10 down-regulated) among females and 16 among males (9 up-regulated and 7 down-regulated). Integrated analysis of the two sets of differentially expressed miRNAs of female and male worms identified 2 miRNAs (sja-miR-3488 and sja-miR-novel_29) that overlapped between female and male datasets. Prediction of miRNA targets and Gene Ontology (GO) term enrichment analysis of the predicted target genes revealed that these genes were involved in some important biological processes, such as nucleic acid metabolic process, macromolecule modification, and cellular aromatic compound metabolic process. The predicted target genes were further matched to the differentially expressed genes in male and female schistosomes from the above two hosts, obtaining 7 genes that may be responsible for regulating the growth, development and sex maturation of schistosomes. Taken together, this study provides the first identification of differentially expressed miRNAs in schistosomes from SCID and BALB/c mice. These miRNAs and their predicted target mRNAs are probably involved in the regulation of development, growth, and maturation of schistosomes. Therefore, this study expands our understanding of schistosome development regulation and host-parasite relationship, and also provides a valuable set of potential anti-schistosomal targets for prevention and control of schistosomiasis.

Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson's disease.

Extensive studies have reported that interaction of α-synuclein amyloid species with neurons is a crucial mechanistic characteristic of Parkinson's disease (PD) and small molecules can downregulate the neurotoxic effects induced by protein aggregation. However, the exact mechanism(s) of these neuroprotective effects by small molecules remain widely unknown. In the present study, α-synuclein samples in the amyloidogenic condition were aged for 120h with or without different concentrations of mitoquinone (MitoQ) as a quinone derivative compound and the amyloid characteristics and the relevant neurotoxicity were evaluated by Thioflavin T (ThT)/Nile red fluorescence, Congo red absorption, circular dichroism (CD), transmission electron microscopy (TEM), cell viability, lactate dehydrogenase (LDH), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), and caspase-9/-3 activity assays. Results clearly showed the capacity of MitoQ on the inhibition of the formation of α-synuclein fibrillation products through modulation of the aggregation pathway by an effect on the kinetic parameters. Also, it was shown that α-synuclein samples aged for 120h with MitoQ trigger less neurotoxic effects against SH-SY5Y cells than α-synuclein amyloid alone. Indeed, co-incubation of α-synuclein with MitoQ reduced the membrane leakage, oxidative and nitro-oxidative stress, modifications of macromolecules, and apoptosis.

A Hypothesis: Fructosamine-3-Kinase-Related-Protein (FN3KRP) Catalyzes Deglycation of Maillard Intermediates Directly Downstream from Fructosamines.

Non-enzymatic glycation (a.k.a. Maillard reaction) is a series of random spontaneous reactions between reducing sugars and amines, resulting in the formation of irreversible advanced glycation endproducts (AGE's). In food chemistry, this process is beneficial by contributing to the flavor, aroma, texture, and appearance of cooked foods. In vivo, however, Maillard reaction is deleterious because uncontrolled modification and crosslinking of biological macromolecules impairs their function. Consequently, chronic hyperglycemia of diabetes mellitus, for instance, leads to increased non-enzymatic glycation and diverse, multi-organ pathologies of diabetic complications. Based on the fact that toxic compounds, such as free radicals, are detoxified in vivo by specific defense mechanisms, one would expect to find mechanisms to control glucose toxicity as well. Thus far, only one such enzyme, fructosamine-3-kinase (FN3K), has been characterized. It operates intracellularly by catalyzing ATP-dependent removal of Maillard adducts, D-fructoselysines, from proteins, thereby reducing the Maillard reaction flux from glucose to AGE's. When FN3K was isolated, a closely related but distinct protein copurified with it. Unlike FN3K, however, this enzyme, fructosamine-3-kinase-related protein (FN3KRP), does not phosphorylate D-fructoselysines but it does phosphorylate several other (non-physiological) substrates. Interestingly, the distribution of FN3KRP in nature appears to be nearly universal whereas that of FN3K is limited to endotherms. In this article, it is suggested that the function of FN3KRP is deglycation of Maillard adducts downstream from fructoselysines. Such a mechanism, if proven correct, would be valuable given reports on apparent correlations between FN3KRP and some chronic conditions and/or diseases, such as a recent publication which proposes that the FN3KRP gene may be a longevity gene.