Regulation Of Enzyme Activity Research Articles

Mitigation of Salinity-Induced Oxidative Damage, Growth, and Yield Reduction in Fine Rice by Sugarcane Press Mud Application.

Salinity stress is one of the major global problems that negatively affect crop growth and productivity. Therefore, ecofriendly and sustainable strategies for mitigating salinity stress in agricultural production and global food security are highly demandable. Sugarcane press mud (PM) is an excellent source of the organic amendment, and the role of PM in mitigating salinity stress is not well understood. Therefore, this study was aimed to investigate how the PM mitigates salinity stress through the regulation of rice growth, yield, physiological properties, and antioxidant enzyme activities in fine rice grown under different salinity stress conditions. In this study, different levels of salinity (6 and 12 dS m–1) with or without different levels of 3, 6, and 9% of SPM, respectively were tested. Salinity stress significantly increased malondialdehyde (MDA, 38%), hydrogen peroxide (H2O2, 74.39%), Na+ (61.5%), electrolyte leakage (40.32%), decreased chlorophyll content (32.64%), leaf water content (107.77%), total soluble protein (TSP, 72.28%), and free amino acids (FAA, 75.27%). However, these negative effects of salinity stress were reversed mainly in rice plants after PM application. PM application (9%) remained the most effective and significantly increased growth, yield, TSP, FAA, accumulation of soluble sugars, proline, K+, and activity of antioxidant enzymes, namely, ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD). Thus, these findings suggest a PM-mediated eco-friendly strategy for salinity alleviation in agricultural soil could be useful for plant growth and productivity in saline soils.

Mechanisms of strengthening energy and mass transfer in microbial conversion of flue-gas-derived CO2 to biodiesel and biogas fuels

The goals of national energy security and sustainable development necessitate the role of renewable energy, of which biomass energy is an essential choice for realizing the strategic energy diversification and building a low-carbon energy system. Microbial conversion of flue-gas-derived CO2 for producing biodiesel and biogas has been considered a significant technology in new energy development. Microalgae carbon sequestration is a hot research direction for researchers. However, three fundamental problems relating to energy/mass transfer and conversion remain as follows: (1) contradictory relationship between high resistance of cell membrane micropores and high flux of flue-gas-derived CO2 limits mass transfer rate of CO2 molecules across cell membrane; (2) low biocatalytic activity of intracellular enzymes with high-concentration CO2 results in difficulties in directional carbon/hydrogen conversion; (3) competition between multiple intracellular reaction pathways and high energy barriers of target products hinder the desirable cascade energy transfer. Therefore, key scientific issues of microbial energy conversion lie in the understanding on directional carbon/hydrogen conversion and desirable cascade energy transfer. Multiple researches have established a theoretical foundation of microbial energy conversion which strengthens energy/mass transfer in microbial cells. The innovative results in previous studies have been obtained as follows: (1) Reveal mass transfer mechanism of vortex flow across cell membrane micropores. (2) Propose a strategy that directionally regulates enzyme activity. (3) Establish chain reaction pathways coupled with step changes.

Compartment-Specific Proximity Ligation Expands the Toolbox to Assess the Interactome of the Long Non-Coding RNA NEAT1

The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1. Interestingly, a growing number of biochemical and genetic tools to assess NEAT1 interactomes has been reported. Here, we discuss the Hybridisation Proximity (HyPro) labeling technique in the context of NEAT1. HyPro labeling is a recently developed method to detect spatially ordered interactions of RNA-containing nuclear compartments in cultured human cells. After introducing NEAT1 and paraspeckles, we describe the advantages of the HyPro technology in the context of other methods to study RNA interactomes, and review the key findings in mapping NEAT1-associated RNA transcripts and protein binding partners. We further discuss the limitations and potential improvements of HyPro labeling, and conclude by delineating its applicability in paraspeckles-related cancer research.

Transcriptomics and Antioxidant Analysis of Two Chinese Chestnut (Castanea mollissima BL.) Varieties Provides New Insights Into the Mechanisms of Resistance to Gall Wasp Dryocosmus kuriphilus Infestation.

Chinese chestnut is a popular fruit tree with a high nutritional value of its nuts, which can suffer from infestation by the chestnut gall wasp Dryocosmus kuriphilus (GWDK) that results in gall formation and resultant loss of production and profitability. The physiological and molecular mechanisms of GWDK resistance found in certain genotypes currently remains elusive. To gain new insights into this phenomenon, a series of RNA-Seq integrated with metabolomic profiling experiments were executed to investigate the chemical and transcriptional differences in response to GWDK infestation in two contrasting chestnut varieties grown in China (the susceptible “HongLi,” HL and the partially resistant “Shuhe_Wuyingli,” SW). Three time points were selected for comparison: The initiation stage (A), growth stage (B), and maturation stage (C). Results showed that concentrations of hydrogen peroxide (H2O2) and the activities of peroxidase (POD) and superoxide dismutase (SOD) enzyme were elevated in the resistant SW leaves compared with those in HL leaves at all three developmental stages, while catalase (CAT) and polyphenol oxidase (PPO) activities were mostly higher in HL leaves. RNA-Seq transcriptomic analyses of HL and SW leaves revealed that various metabolic pathways involved in GWDK stress responses, such as plant hormone signal transduction, MAPK signaling, and the peroxisome pathway, were enriched in the contrasting samples. Moreover, the weighted gene co-expression network analysis (WGCNA) of differentially expressed genes in the POD pathway combined with transcription factors (TFs) indicated that the expression of TF members of bHLH, WRKY, NAC, and MYB family positively correlated with POD pathway gene expression. The TFs CmbHLH130 (EVM0032437), CmWRKY31 (EVM0017000), CmNAC50 (EVM0000033), and CmPHL12 (EVM0007330) were identified as putative TFs that participate in the regulation of insect-induced plant enzyme activities in chestnut, which may contribute to GWDK resistance in SW. Expression levels of 8 random differentially expressed genes (DEGs) were furthermore selected to perform quantitative reverse transcription PCR (qRT-PCR) to validate the accuracy of the RNA-Seq-derived expression patterns. This study guides the functional analyses of further candidate genes and mechanisms important for GWDK resistance in chestnuts in the future as well as can help in identifying the master transcriptional regulators and important enzyme steps that support major insect defense pathways in chestnut.

The Status and Prospects of Epigenetics in the Treatment of Lymphoma.

The regulation of gene transcription by epigenetic modifications is closely related to many important life processes and is a hot research topic in the post-genomic era. Since the emergence of international epigenetic research in the 1990s, scientists have identified a variety of chromatin-modifying enzymes and recognition factors, and have systematically investigated their three-dimensional structures, substrate specificity, and mechanisms of enzyme activity regulation. Studies of the human tumor genome have revealed the close association of epigenetic factors with various malignancies, and we have focused more on mutations in epigenetically related regulatory enzymes and regulatory recognition factors in lymphomas. A number of studies have shown that epigenetic alterations are indeed widespread in the development and progression of lymphoma and understanding these mechanisms can help guide clinical efforts. In contrast to chemotherapy which induces cytotoxicity, epigenetic therapy has the potential to affect multiple cellular processes simultaneously, by reprogramming cells to achieve a therapeutic effect in lymphoma. Epigenetic monotherapy has shown promising results in previous clinical trials, and several epigenetic agents have been approved for use in the treatment of lymphoma. In addition, epigenetic therapies in combination with chemotherapy and/or immunotherapy have been used in various clinical trials. In this review, we present several important epigenetic modalities of regulation associated with lymphoma, summarize the corresponding epigenetic drugs in lymphoma, and look at the future of epigenetic therapies in lymphoma.

SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases.

Topoisomerases play crucial roles in DNA metabolism that include replication, transcription, recombination, and chromatin structure by manipulating DNA structures arising in double-stranded DNA. These proteins play key enzymatic roles in a variety of cellular processes and are also likely to play structural roles. Topoisomerases allow topological transformations by introducing transient breaks in DNA by a transesterification reaction between a tyrosine residue of the enzyme and DNA. The cleavage reaction leads to a unique enzyme intermediate that allows cutting DNA while minimizing the potential for damage-induced genetic changes. Nonetheless, topoisomerase-mediated cleavage has the potential for inducing genome instability if the enzyme-mediated DNA resealing is impaired. Regulation of topoisomerase functions is accomplished by post-translational modifications including phosphorylation, polyADP-ribosylation, ubiquitylation, and SUMOylation. These modifications modulate enzyme activity and likely play key roles in determining sites of enzyme action and enzyme stability. Topoisomerase-mediated DNA cleavage and rejoining are affected by a variety of conditions including the action of small molecules, topoisomerase mutations, and DNA structural forms which permit the conversion of the short-lived cleavage intermediate to persistent topoisomerase DNA–protein crosslink (TOP-DPC). Recognition and processing of TOP-DPCs utilizes many of the same post-translational modifications that regulate enzyme activity. This review focuses on SUMOylation of topoisomerases, which has been demonstrated to be a key modification of both type I and type II topoisomerases. Special emphasis is placed on recent studies that indicate how SUMOylation regulates topoisomerase function in unperturbed cells and the unique roles that SUMOylation plays in repairing damage arising from topoisomerase malfunction.

A network pharmacology technique used to investigate the potential mechanism of Ligustilide's effect on atherosclerosis.

Ligustilide (LIG) is a major active ingredient in traditional Chinese medicines that is also found in plant rhizomes such as carrot, coriander, and others, and it has been demonstrated to have cardiovascular preventive benefits. However, the mechanisms through which LIG protects the cardiovascular and cerebrovascular systems in atherosclerosis (AS) remain unknown. This study was aimed to investigate the mechanisms of LIG in AS utilizing the network pharmacology and molecular docking, and then to validate the putative mechanism through experiments. The network pharmacological analysis indicated that a total of 55 were performed on LIG and AS intersection targets. The genes of LIG and AS intersection targets enriched in the regulation of receptor and enzyme activity, cytokines-related, and transcription factors, indicating that these targets were primarily involved in cell proliferation and migration, regulating cell differentiation and skeletal activities in the development of AS. Finally, molecular docking was used to validate the major targets of LIG and AS intersection targets. Further experiments revealed that LIG may inhibit cell migration induced by AngII by reducing calcium influx, and regulating phenotypic translation-related proteins SM-22α and OPN. The present study investigated the potential targets and signaling pathways of LIG, which provides new insight into its anti-atherosclerosis actions in terms of reducing inflammation, cell proliferation, and migration, and may constitute a novel target for the treatment of AS. PRACTICAL APPLICATIONS: LIG has been shown to have cardiovascular protective benefits, the mechanism by which it protects the cardiovascular and cerebrovascular systems in AS remains unknown. This study uses a holistic network pharmacology strategy to investigate putative treatment pathways and conducts exploratory experimentation. The findings demonstrate that LIG reduces VSMC migration in the treatment of AS, acts as an anti-inflammatory agent, and prevents excessive cell proliferation and migration. Finally, the goal of our research is to uncover the molecular mechanism of LIG's influence on AS. The findings will provide a new research avenue for LIG as well as suggestions for the study of other herbal treatments. These research results will provide a new research direction for LIG and provide guidance for the research of other herbal medicines. This work revealed the multi-component, multi-target, multi-pathway, and multi-disease mechanism of LIG.

Perseus plugin “Metis” for metabolic-pathway-centered quantitative multi-omics data analysis for static and time-series experimental designs

SummaryWe introduce Metis, a new plugin for the Perseus software aimed at analyzing quantitative multi-omics data based on metabolic pathways. Data from different omics types are connected through reactions of a genome-scale metabolic-pathway reconstruction. Metabolite concentrations connect through the reactants, while transcript, protein, and protein post-translational modification (PTM) data are associated through the enzymes catalyzing the reactions. Supported experimental designs include static comparative studies and time-series data. As an example for the latter, we combine circadian mouse liver multi-omics data and study the contribution of cycles of phosphoproteome and metabolome to enzyme activity regulation. Our analysis resulted in 52 pairs of cycling phosphosites and metabolites connected through a reaction. The time lags between phosphorylation and metabolite peak show non-uniform behavior, indicating a major contribution of phosphorylation in the modulation of enzymatic activity.

Effects of Janus kinase (JAK) on hemocyte proliferation and disease resistance in Scylla paramamosain

Janus kinase (JAK), a nonreceptor tyrosine kinase, is the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In this study, RNA interference technology was used to knockdown the expression of JAK to explore the immune function of JAK in Scylla paramamosain. JAK expression was relatively high in the intestine and relatively low in the heart and hemocytes of S. paramamosain. JAK was highly expressed in all examined tissues of S. paramamosain after infection with white spot syndrome virus (WSSV) or Vibrio alginolyticus. The expression levels of Astakine, STAT, CAP, TLR, proPO, and CTL were downregulated, while MCM7, Myosin and Relish expression was upregulated in hemocytes at 24 h after injection of JAK-dsRNA. Astakine expression was significantly downregulated within 72 h after injection of JAK-dsRNA. The total hemocyte count and hemocyte proliferation were significantly decreased after treatment with Astakine-dsRNA or JAK-dsRNA. The results showed that JAK may promote hemocyte proliferation, probably by regulating Astakine expression. The activities of phenoloxidase, superoxide dismutase, and lysozyme were decreased significantly, while production of reactive oxygen species was increased significantly in hemocytes after treatment with JAK-dsRNA. After JAK knockdown, the phagocytosis rate of WSSV or V. alginolyticus in hemocytes was increased. After WSSV challenge, the WSSV copy number in the JAK-dsRNA-treated group was higher than that in the WSSV group. After V. alginolyticus challenge, the apoptosis rate of hemocytes in the JAK-dsRNA group was higher than that in the V. alginolyticus group. The mortality rate of WSSV or V. alginolyticus-infected crabs after JAK knockdown was higher than that of the infection group. These results suggest that JAK can regulate the expression of some immune-related genes, such as Astakine, to influence the innate immune response of S. paramamosain against pathogens (WSSV or V. alginolyticus), mostly by regulating enzyme activities, hemocyte phagocytosis and apoptosis.

Physiological and Biochemical Responses of Kandelia obovata to Upwelling Stress

Mangroves growing in intertidal areas are faced with various stresses caused by coastal human activities and oceanic and atmospheric sources. Although the study of the physiological and biochemical characteristics of mangroves has been developing over the past four decades, the effect of upwelling on mangroves in plants stress resistance has seldom been investigated. Here, changes in the physiological and biochemical characteristics of the leaves of Kandelia obovata seedlings in response to upwelling were investigated (air temperature: 25 °C; water temperature: control 25 °C, 13 °C, and 5 °C; salinity: 10‰). The results revealed that upwelling treatment caused an increase in chlorophyll content but a decrease in photosynthetic fluorescence parameters. Hydrogen peroxide (H2O2) production and malondialdehyde activity (MDA) increased with the decrease in upwelling temperature. The proline content increased under upwelling stress, whereas the soluble sugar content decreased. Further, the activities of antioxidant enzymes, such as superoxide dismutase activity (SOD) and peroxidase activity (POD), showed an increasing trend during the treatment, while catalase activity (CAT) decreased. It was evidenced that upwelling stress triggered the physiological and biochemical responses of Kandelia obovata seedlings. This effect became more intense as the upwelling temperature decreased, and all these indicators showed different responses to upwelling stress. Through synthesizing more energy and regulating enzyme activity and osmotic pressure, the leaves of K. obovata formed a resistance mechanism to short-term upwelling.

Activation and thermal stabilization of a recombinant γ-glutamyltranspeptidase from Bacillus licheniformis ATCC 27811 by monovalent cations.

The regulation of enzyme activity through complexation with certain metal ions plays an important role in many biological processes. In addition to divalent metals, monovalent cations (MVCs) frequently function as promoters for efficient biocatalysis. Here, we examined the effect of MVCs on the enzymatic catalysis of a recombinant γ-glutamyltranspeptidase (BlrGGT) from Bacillus licheniformis ATCC 27,811 and the application of a metal-activated enzyme to L-theanine synthesis. The transpeptidase activity of BlrGGT was enhanced by Cs+ and Na+ over a broad range of concentrations with a maximum of 200mM. The activation was essentially independent of the ionic radius, but K+ contributed the least to enhancing the catalytic efficiency. The secondary structure of BlrGGT remained mostly unchanged in the presence of different concentrations of MVCs, but there was a significant change in itstertiary structure under the same conditions. Compared with the control, the half-life (t1/2) of the Cs+-enriched enzyme at 60 and 65°C was shown to increase from 16.3 and 4.0min to 74.5 and 14.3min, respectively. The simultaneous addition of Cs+ and Mg2+ ions exerted a synergistic effect on the activation of BlrGGT. This was adequately reflected by an improvement in the conversion of substrates to L-theanine by 3.3-15.1% upon the addition of 200mM MgCl2 into a reaction mixture comprising the freshly desalted enzyme (25μg/mL), 250mM L-glutamine, 600mM ethylamine, 200mM each of the MVCs, and 50mM borate buffer (pH 10.5). Taken together, our results provide interesting insights into the complexation of MVCs with BlrGGT and can therefore be potentially useful to the biocatalytic production of naturally occurring γ-glutamyl compounds. KEY POINTS: • The transpeptidase activity of B. licheniformisγ-glutamyltranspeptidase can be activated by monovalent cations. • The thermal stability of the enzyme was profoundly increased in the presence of 200mM Cs+. • The simultaneous addition of Cs+and Mg2+ions to the reaction mixture improves L-theanine production.

Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?

Adenosine deaminase (ADA) is a purine metabolism enzyme that catalyses the breakdown of adenosine and deoxyadenosine. The enzyme is important in several cellular processes, including the innate immune response and cellular differentiation, and it is also an important enzyme for the maintenance of brain homeostasis, in part due to its regulation of adenosine. Aberrant regulation of ADA enzyme activity has been linked to several neurodegenerative diseases and diseases that can result in neurological impairment. However, the mechanisms behind altered ADA regulation and how this leads to the development of neurological dysfunction are poorly characterised. This review summarises the current research on ADA and its role and regulation in disease pathology, with a focus on the central nervous system (CNS) and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS).

Detection of the chemical changes in blood, liver, and brain caused by electromagnetic field exposure using Raman spectroscopy, biochemical assays combined with multivariate analyses

The effects of the electromagnetic field on living organisms have been studied for several years. In this article, we showed what kind of cold change an extremely low-frequency electromagnetic field (ELF-MF) exposure 500 μT 50 Hz by using a Meritt Coil System causes in the samples of the brain and liver samples. To measure oxidative load, we measured malondialdehyde (MDA) and glutathione (GSH) levels. To identify the chemical changes, we collected Raman spectra of cerebellum, left brain, right brain and liver tissue from the control group of animals and from the animal, which were exposed to an electromagnetic field (ELF-MF group). Obtained results showed, that lipid peroxidation was increased and the antioxidant response was decreased. In the brain samples the shift of peaks corresponding to the amide III vibrations existed after ELF-MF exposure. Structural changes were detected in CH2 vibrations originating from lipids in both hemispheres. Additionally, the number of amide III bonds was increased with ELF-MF exposure in the cerebellum and left-brain tissue. In liver tissue higher Raman intensities were visible in the tissues from the ELF-MF group. In this group electromagnetic field also caused structural changes in lipids. Principal component analysis (PCA) showed, that it is possible to distinguish ELF-MF and control groups. Consequently, hierarchical component analysis (HCA) showed that tissues from ELF-MF and control groups separately created similarity with the groups. Obtained results suggest that the electromagnetic field caused structural and quantitative chemical changes in brain and liver tissue. Additionally, present data suggest that ELF-MF plays an important role in the regulation of enzyme activity and has effects on biochemical processes, possibly improved by production of ROS.

Abnormal behavior of chilling injury in postharvest papaya fruit is associated with sugar metabolism.

In the most chilling-sensitive fruits and vegetables, usually, the lower the storage temperature, the more serious the symptoms of chilling injury (CI). As one of the special cases, papaya fruits at 1℃ show slighter CI symptoms than those at higher storage temperature. Such abnormal CI phenomenon has not received enough attention and its mechanism is not clear. The present study investigated the difference of CI severity and sugar metabolism in papaya fruits when stored between 1℃ and 6℃. The results showed that CI index in papaya fruits preserved at 1°C was markedly lower than that in fruit at 6°C, which was accompanied by higher content of glucose, fructose, and sucrose. In addition, compared to 6°C, 1°C promoted higher activities of sucrose synthase, sucrose-phosphate synthase, and neutral invertase, but lowered acid invertase activity. RT-qPCR analysis showed that 1°C upregulated the CpSPS expression and downregulated the CpAI expression when compared to 6°C. The present results indicate that higher chilling tolerance in papaya fruit at 1°C could be attributed to more accumulation of sucrose and reducing sugars in relation to more advantageous sugar metabolism. These results provided a basis for explaining the abnormal behavior of papaya fruits in response to varying low temperatures. PRACTICAL APPLICATION: For most chilling-sensitive fruits and vegetables, in the range of temperatures that induce chilling injury (CI), the lower storage temperature may lead to more severe CI. However, as one of the special cases, papaya fruits at 1℃ show slighter CI symptoms than those at higher storage temperature. The reason for this abnormal CI symptom in papaya fruits is that 1°C storage can regulated enzyme activities and changes in gene expression related to sugar metabolism, which could result in more accumulation of sucrose and slower degradation of hexose and contribute to alleviation of CI. Our results provided a basis for explaining the abnormal behavior of papaya fruit in response to varying low temperatures.

Linking Increased Isotope Fractionation at Low Concentrations to Enzyme Activity Regulation: 4-Cl Phenol Degradation by Arthrobacter chlorophenolicus A6.

Slow microbial degradation of organic trace chemicals (“micropollutants”) has been attributed to either downregulation of enzymatic turnover or rate-limiting substrate supply at low concentrations. In previous biodegradation studies, a drastic decrease in isotope fractionation of atrazine revealed a transition from rate-limiting enzyme turnover to membrane permeation as a bottleneck when concentrations fell below the Monod constant of microbial growth. With degradation of the pollutant 4-chlorophenol (4-CP) by Arthrobacter chlorophenolicus A6, this study targeted a bacterium which adapts its enzyme activity to concentrations. Unlike with atrazine degradation, isotope fractionation of 4-CP increased at lower concentrations, from ε(C) = −1.0 ± 0.5‰ in chemostats (D = 0.090 h–1, 88 mg L–1) and ε(C) = −2.1 ± 0.5‰ in batch (c0 = 220 mg L–1) to ε(C) = −4.1 ± 0.2‰ in chemostats at 90 μg L–1. Surprisingly, fatty acid composition indicated increased cell wall permeability at high concentrations, while proteomics revealed that catabolic enzymes (CphCI and CphCII) were differentially expressed at D = 0.090 h–1. These observations support regulation on the enzyme activity level—through either a metabolic shift between catabolic pathways or decreased enzymatic turnover at low concentrations—and, hence, reveal an alternative end-member scenario for bacterial adaptation at low concentrations. Including more degrader strains into this multidisciplinary analytical approach offers the perspective to build a knowledge base on bottlenecks of bioremediation at low concentrations that considers bacterial adaptation.

Natural Products as Sources of Multitarget Compounds: Advances in the Development of Ferulic Acid as Multitarget Therapeutic.

Nature has provided therapeutic substances for millennia, with many valuable medications derived from plant sources. Multitarget drugs become essential in the management of various disorders, including hepatic disorders, neurological disorders, diabetes, and carcinomas. Ferulic acid is a significant potential therapeutic agent, which is easily available at low cost, possesses a low toxicity profile, and has minimum side effects. Ferulic acid exhibits various therapeutic actions by modulation of various signal transduction pathways such as Nrf2, p38, and mTOR. The actions exhibited by ferulic acid include anti-apoptosis, antioxidant, anti-inflammatory, antidiabetic, anticarcinogenic, hepatoprotection, cardioprotection, activation of transcriptional factors, expression of genes, regulation of enzyme activity, and neuroprotection, which further help in treating various pathophysiological conditions such as cancer, skin diseases, brain disorders, diabetes, Parkinson's disease, Alzheimer's disease, hypoxia, hepatic disorders, H1N1 flu, and viral infections. The current review focuses on the significance of natural products as sources of multitarget compounds, and a primary focus has been made on ferulic acid and its mechanism, role, and protective action in various ailments.

Effects of hypoxia and acidification stress on ion regulation and gill structure of juvenile Larimichthys crocea.

To investigate the ion regulation of large yellow croaker (Larimichthys crocea) under hypoxia and acidification stresses, we investigated the effects of hypoxia (dissolved oxygen DO 3.5 mg·L-1, pH 8.1), acidification (DO 7.0 mg·L-1, pH 7.35) and combined stresses of hypoxia and acidification (DO 3.5 mg·L-1, pH 7.35) on gill tissue structure and physiological indices related to ion regulation of juvenile L. croaker. The results showed that, under hypoxia stress, gill Na+/K+-ATPase activity, serum Na+, Ca2+ and Cl- contents of juvenile L. croaker decreased first and then increased. Under acidification stress, gill Ca2+-ATPase activity, serum Na+ and Ca2+ contents of juvenile L. croaker increased first and then decreased. Under the combined stresses of hypoxia and acidification, Na+/K+-ATPase activity and Na+, K+ and Ca2+ contents increased first and then decreased, while Ca2+-ATPase activity and Cl- content decreased first and then increased. The results of gill histology showed that hypoxia and acidification stresses led to the detachment of gill epithelial cells, and the combined stresses of hypoxia and acidification led to proliferation, hypertrophy and swelling of gill epithelial cells. Comprehensive analysis showed that hypoxia and acidification stress affected the activities of major ion regulatory enzymes in juvenile L. croaker and caused different degrees of damage to gill tissue, resulting in imbalanced ion regulation in juvenile L. croaker.

Magnetism-Controllable Catalytic Activity of DNAzyme.

Controllable regulation of enzyme activity is an important prerequisite for the in-depth application of enzymes, especially in today's intelligent era. However, irreversible regulation and cumbersome operation make this goal difficult to achieve. Here, by adopting magnetism and a harmless, noncontact, and time- and space-controllable physical element, we developed a system that could conveniently and reversibly regulate the activity of DNAzyme. In this system, the strands of the DNAzyme could be stretched or folded by applying or removing a magnetic field. Thereby, the conformation-dependent endonuclease activity of the DNAzyme could be facilely switched between an "OFF" and "ON" state. This system provides a reusable platform for the control of enzyme catalytic activity through magnetism, which provides guidance for further application in some related scientific research, especially the regulation of the activity of conformation-dependent polymers (DNAzymes, aptamers, and peptides).

Clonidine and Brain Mitochondrial Energy Metabolism: Pharmacodynamic Insights Beyond Receptorial Effects.

Clonidine is an anti-hypertensive drug that inhibits the release of norepinephrine from pre-synaptic terminals binding to pre-synaptic α2-adrenoreceptors. Some studies suggest that this drug decreases brain energy expenditure, particularly in hypoxic-ischemic injury. However, data about clonidine effects on the functional parameters regulating brain energy metabolism are lacking. In this study, the effects of acute clonidine treatment (5μg×kg-1 i.p., 30min) were evaluated on the catalytic activity of regulatory energy-linked enzymes of Krebs' cycle, Electron Transport Chain and glutamate metabolism of temporal cerebral cortex of 3-month-old male Sprague-Dawley rats. Enzyme activities were assayed on non-synaptic "free" mitochondria (FM) of neuronal perikaryon and partly of glial cells, and on intra-synaptic "light" (LM) and "heavy" mitochondria (HM), localized within synaptic terminals. This subcellular analysis differentiates clonidine effects on post-synaptic and pre-synaptic neuronal compartments. The results showed that clonidine increased citrate synthase, cytochrome oxidase and glutamate-oxaloacetate transaminase activities of FM. In LM, citrate synthase activity was decreased, while cytochrome oxidase and glutamate-oxaloacetate transaminase activities were increased; on the contrary, citrate synthase, cytochrome oxidase and glutamate dehydrogenase were all decreased in HM. Therefore, clonidine exerted different effects with respect to brain mitochondria, coherently with the in vivo energy requirements of each synaptic compartment: the drug increased energy-linked enzyme activities in post-synaptic compartment, while the metabolic variations were complex in the pre-synaptic one, being enzyme activities heterogeneously modified in LM and decreased in HM. This study highlights the relationships existing between the clonidine-induced neuroreceptorial effects and the energy metabolism in pre- and post- synaptic bioenergetics.

Asymmetric Interaction of Neuropeptidase Activities between Cortico-Limbic Structures, Plasma and Cardiovascular Function after Unilateral Dopamine Depletions of the Nigrostriatal System.

In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior. The study of the activity of neuropeptide regulatory enzymes (neuropeptidases, NPs) is illustrative. We have observed that the left and right brain areas interact intra- and inter-hemispherically, as well as with peripheral tissues or with physiological parameters such as blood pressure or with behaviors such as turning preference. To obtain data that reflect this integrative behavior, we simultaneously analyzed the impact of left or right brain DA depletion on the activity of various NPs in corticolimbic regions of the left and right hemispheres, such as the medial prefrontal cortex, amygdala and hippocampus, as well as on the plasma activity of the same aminopeptidase activities (APs) and on systolic blood pressure (SBP). Intra- and inter-hemispheric interactions as well as the interactions of NPs from the left or right hemispheres were analyzed with the same plasma APs and the SBP obtained from sham and from left or right lesioned rats. The results demonstrate a complex profile depending on the hemisphere considered. They definitively confirm an asymmetric neurovisceral integration and reveal a higher level of inter-hemispheric corticolimbic interactions including with SBP after left dopamine depletion.