Incorporation of 203Hg into methylmercury in fish liver: Studies on biochemical mechanisms in vitro

1975 ◽  
Vol 10 (2) ◽  
pp. 224-235 ◽  
Author(s):  
F. Matsumura ◽  
Y.Gotoh Doherty ◽  
K. Furukawa ◽  
G.M. Boush
Keyword(s):  
Fish Liver ◽  
Biochemical Mechanisms

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

scholarly journals The Occurrence and Biological Activity of Tormentic Acid—A Review

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3797
Author(s):  
Marta Olech ◽  
Wojciech Ziemichód ◽  
Natalia Nowacka-Jechalke
Keyword(s):  
Biological Activity ◽  
Plant Species ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Natural Sources ◽  
Anti Cancer ◽  
Biochemical Mechanisms ◽  
Tormentic Acid

This review focuses on the natural sources and pharmacological activity of tormentic acid (TA; 2α,3β,19α-trihydroxyurs-2-en-28-oic acid). The current knowledge of its occurrence in various plant species and families is summarized. Biological activity (e.g., anti-inflammatory, antidiabetic, antihyperlipidemic, hepatoprotective, cardioprotective, neuroprotective, anti-cancer, anti-osteoarthritic, antinociceptive, antioxidative, anti-melanogenic, cytotoxic, antimicrobial, and antiparasitic) confirmed in in vitro and in vivo studies is compiled and described. Biochemical mechanisms affected by TA are indicated. Moreover, issues related to the biotechnological methods of production, effective eluents, and TA derivatives are presented.

Potential role of multiple members of the kallikrein-related peptidase family of serine proteases in activating latent TGFβ1 in semen

2010 ◽  
Vol 391 (1) ◽  
Author(s):  
Nashmil Emami ◽  
Eleftherios P. Diamandis
Keyword(s):  
Conformational Changes ◽  
Seminal Plasma ◽  
Serine Proteases ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β1 ◽  
Peptide Fragments ◽  
Biochemical Mechanisms

Abstract Transforming growth factor β1 (TGFβ1) has been implicated as a key contributor of immunosuppression in seminal plasma. The biochemical mechanisms that lead to production of active seminal TGFβ1 are not fully understood. It is plausible that TGFβ1 activation is partly induced simultaneously with the release of motile spermatozoa following liquefaction of the semen coagulum. Several members of the kallikrein-related peptidase (KLK) family are involved in the regulation of semen liquefaction. This study examines the involvement of these KLKs in TGFβ1 activation in vitro and ex vivo, in seminal plasma. Latent TGFβ1 was rapidly activated by KLK14. The latency-associated propeptide (LAP) was shown to be cleaved by KLK14 into small peptide fragments, providing a possible mechanism for TGFβ1 activation. KLK14 also cleaved the latent TGFβ binding protein 1 (LTBP1). KLK1, 2, and 5 might also contribute to TGFβ1 activation by nicking the LAP motif and inducing conformational changes that aid in subsequent processing of LAP or through LTBP1 cleavage. Our study provides strong evidence for the involvement of multiple members of the seminal KLK cascade in activation of latent TGFβ1 in seminal plasma. These findings might have clinical implications in infertility treatment of cases with concurrent delayed liquefaction and TGFβ1-related semen antigenicity.

ASEPTIC BROOMRAPE INFECTION OF TOMATO ROOT CULTURE

1996 ◽  
Vol 44 (2-3) ◽  
pp. 89-94 ◽  
Author(s):  
Dalia Losner-Goshen ◽  
Graham Ben-Hod ◽  
M. Alfred Mayer ◽  
Daniel Joel M.
Keyword(s):  
Culture Media ◽  
Root Culture ◽  
Petri Dish ◽  
The Other ◽  
Tomato Root ◽  
In Vitro System ◽  
Host Root ◽  
Biochemical Mechanisms ◽  
Root Tissues

The parasitic plants of the genus Orobanche (broomrape) are important pathogens of numerous agricultural crops throughout the world. The understanding of biochemical mechanisms involved in the penetration of Orobanche haustorium into host root tissues faces difficulties due to the presence of microorganisms. Here we describe an aseptic in vitro system, in which normal broomrape seedlings infect host roots grown in culture, instead of the previously reported infection of intact host plants by Orobanche calli. This system is based on divided Petri plates with two different culture media: one part of the dish contains a rich medium suitable for the support of host root culture, the other part contains a medium with no organic nutrients and no hormones and is therefore suitable for infection of host roots by Orobanche. Roots that are supported by the first medium pass to the other side of the petri dish where they stimulate broomrape seed germination and are infected by the emerging broomrape seedlings.

Detoxification of succinate semialdehyde in Arabidopsis glyoxylate reductase and NAD kinase mutants subjected to submergence stress

Botany ◽  
2012 ◽  
Vol 90 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Wendy L. Allan ◽  
Kevin E. Breitkreuz ◽  
Jeffrey C. Waller ◽  
Jeffrey P. Simpson ◽  
Gordon J. Hoover ◽  
...  
Keyword(s):  
Time Course ◽  
Oxygen Deficiency ◽  
Transcript Abundance ◽  
Redox Status ◽  
Nad Kinase ◽  
Submergence Stress ◽  
Succinate Semialdehyde ◽  
Biochemical Mechanisms ◽  
Glyoxylate Reductase

Succinate semialdehyde (SSA) is a mitochondrially generated intermediate in the metabolism of γ-aminobutyrate (GABA), which accumulates in response to a variety of biotic and abiotic stresses. SSA can be reduced to γ-hydroxybutyrate (GHB) in plants exposed to various abiotic stress conditions. Recent evidence indicates that distinct cytosolic and plastidial glyoxylate reductase isoforms from Arabidopsis thaliana (L.) Heynh (GLYR1 and GLYR2, respectively) catalyze the in vitro conversion of SSA to GHB, as well as glyoxylate to glycolate, via NADPH-dependent reactions. In the present study, recombinant Arabidopsis GLYR1 was demonstrated to catalyze the NADPH-dependent reduction of both glyoxylate and SSA simultaneously to glycolate and GHB, respectively. Six-hour time-course experiments with intact vegetative wild-type Arabidopisis plants subjected to submergence demonstrated that GHB accumulates in rosette leaves, and this is accompanied by increasing levels of GABA and alanine, NADH/NAD+ and NADPH/NADP+ ratios, and GLYR1 and GLYR2 transcript abundance. The use of GLYR (glyr1 or glyr2 knockout) and NAD kinase1 (NADK1 suppression or overexpression) mutants demonstrated that under submergence the production of GHB is mediated via both GLYR isoforms, the loss of either GLYR1 or GLYR2 activity influences redox status and the levels of GABA and alanine, and the manipulation of NADP(H) availability, specifically in the cytosol, influences the production of GHB. These results suggest that biochemical mechanisms are more important than transcriptional mechanisms in the regulation of GLYR activity and SSA detoxification in plants during the onset of submergence-induced oxygen deficiency.

scholarly journals Evolution of Enterococcus faecium to A Combination of Daptomycin and Fosfomycin Reveals Distinct and Diverse Adaptive Strategies

2021 ◽  
Author(s):  
Adeline Supandy ◽  
Heer H Mehta ◽  
Truc T Tran ◽  
William R Miller ◽  
Rutan Zhang ◽  
...  
Keyword(s):  
Enterococcus Faecium ◽  
Adaptive Strategies ◽  
Membrane Dynamics ◽  
Combination Therapies ◽  
Front Line ◽  
Important Public Health ◽  
Public Health Threat ◽  
Biochemical Mechanisms ◽  
Vancomycin Resistant

Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) are an important public health threat. VREfm have become increasingly resistant to the front-line antibiotic, daptomycin (DAP). As such, the use of DAP combination therapies (like fosfomycin [FOS]), has received increased attention. Antibiotic combinations could extend the efficacy of current available antibiotics and potentially delay the onset of further resistance. We investigated the potential for E. faecium HOU503, a clinical VREfm isolate that is DAP and FOS susceptible, to develop resistance to a DAP-FOS combination. Of particular interest was whether the genetic drivers for DAP-FOS resistance might be epistatic and, thus, potentially decrease the efficacy of a combinatorial approach in either inhibiting VREfm or in delaying the onset of resistance. We show that resistance to DAP-FOS could be achieved by independent mutations to proteins responsible for cell wall synthesis for FOS and in altering membrane dynamics for DAP. However, we did not observe genetic drivers that exhibited substantial cross-drug epistasis that could undermine DAP-FOS combination. Of interest was that FOS resistance in HOU503 was largely mediated by changes in phosphoenolpyruvate (PEP) flux as a result of mutations in pyruvate kinase (pyk). Increasing PEP flux could be a readily accessible mechanism for FOS resistance in many pathogens. Importantly, we show that HOU503 were able to develop DAP resistance through a variety of biochemical mechanisms and were able to employ different adaptive strategies. Finally, we showed that the addition of FOS can prolong the efficacy of DAP, significantly extending the timeline to resistance in vitro.

scholarly journals New methods for monitoring mitochondrial biogenesis and mitophagy in vitro and in vivo

2017 ◽  
Vol 242 (8) ◽  
pp. 781-787 ◽  
Author(s):  
Jessica A Williams ◽  
Katrina Zhao ◽  
Shengkan Jin ◽  
Wen-Xing Ding
Keyword(s):  
Cell Differentiation ◽  
Blood Cell ◽  
Tissue Injury ◽  
Animal Tissues ◽  
Drug Induced ◽  
Cellular Homeostasis ◽  
New Methods ◽  
Biochemical Mechanisms

Removal of damaged mitochondria through mitophagy is critical for maintaining cellular homeostasis and functions. Increasing evidence implicates mitophagy in red blood cell differentiation, neurodegeneration, macrophage-mediated inflammation, ischemia, adipogenesis, drug-induced tissue injury, and cancer. Considerable progress has been made toward understanding the biochemical mechanisms involved in mitophagy regulation. However, few reliable assays to monitor and quantify mitophagy have been developed, particularly in vivo. In this review, we summarize the recent development of three assays, MitoTimer, mt-Keima and mito-QC, for monitoring and quantifying mitophagy in cells and in animal tissues. We also discuss the advantages and limitations of these three assays when using them to monitor and quantify mitophagy. Impact statement Removal of damaged mitochondria through mitophagy is critical for maintaining cellular homeostasis and functions. However, reliable quantitative assays to monitor mitophagy, particularly in vivo, are just emerging. This review will summarize the current novel quantitative assays to monitor mitophagy in vivo.

In vitro biotransformation rates in fish liver S9: Effect of dosing techniques

2014 ◽  
Vol 33 (8) ◽  
pp. 1885-1893 ◽  
Author(s):  
Yung-Shan Lee ◽  
Danny H.Y. Lee ◽  
Maximilien Delafoulhouze ◽  
S. Victoria Otton ◽  
Margo M. Moore ◽  
...  
Keyword(s):  
Fish Liver

scholarly journals Myo-Inositol Safety in Pregnancy: From Preimplantation Development to Newborn Animals

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Nilay Kuşcu ◽  
Mariano Bizzarri ◽  
Arturo Bevilacqua
Keyword(s):  
Assisted Reproduction ◽  
Physiological Role ◽  
Blastocyst Stage ◽  
Culture Conditions ◽  
Preimplantation Development ◽  
Preimplantation Embryos ◽  
Developmental Patterns ◽  
Cellular Processes ◽  
Biochemical Mechanisms

Myo-inositol (myo-Ins) has a physiological role in mammalian gametogenesis and embryonic development and a positive clinical impact on human medically assisted reproduction. We have previously shown that mouse embryo exposure to myo-Ins through preimplantation developmentin vitroincreases proliferation activity and blastocyst production, representing an improvement in culture conditions. We have herein investigated biochemical mechanisms elicited by myo-Ins in preimplantation embryos and evaluated myo-Ins effects on postimplantation/postnatal development. To this end naturally fertilized embryos were culturedin vitroto blastocyst in the presence or absence of myo-Ins and analyzed for activation of the PKB/Akt pathway, known to modulate proliferation/survival cellular processes. In parallel, blastocyst-stage embryos were transferred into pseudopregnant females and allowed to develop to term and until weaning. Results obtained provide evidence that myo-Ins induces cellular pathways involving Akt and show that (a) exposure of preimplantation embryos to myo-Ins increases the number of blastocysts available for uterine transfer and of delivered animals and (b) the developmental patterns of mice obtained from embryos cultured in the presence or absence of myo-Ins, up to three weeks of age, overlap. These data further identify myo-Ins as a possibly important supplement for human preimplantation embryo culture in assisted reproduction technology.

Effects of Bisphosphonate on Long-Term Culture of Cartilage Allografts

2013 ◽  
Author(s):  
Yilu Zhou ◽  
Lauren Resutek ◽  
Liyun Wang ◽  
X. Lucas Lu
Keyword(s):  
Medial Meniscus ◽  
Biomechanical Properties ◽  
Culture Conditions ◽  
Protective Mechanisms ◽  
Post Traumatic ◽  
Biochemical Mechanisms ◽  
Altered Metabolism

Zoledronic acid (ZA), an FDA approved bisphosphonate (BP) medicine, is widely used for the treatment of osteoclast-related bone loss diseases [1]. Our previous study has found that systemic administration of ZA could dramatically suppress the development of post-traumatic osteoarthritis (PTOA) in the DMM (destabilization of the medial meniscus) mouse model, a model recapitulating the altered joint loading associated with PTOA [2]. This finding is consistent with a few similar studies using different animal models [3]. However, little is known about the cellular and biochemical mechanisms of BP mediated chondro-protection in PTOA pathogenesis. Studies have shown that PTOA often initiates from the apoptosis and altered metabolism of cartilage chondrocytes. In this study, we will investigate the direct effects of ZA on the metabolisms of chondrocytes using long-term in vitro culture of cartilage allografts. As one of the earliest responses of chondrocytes to mechanical stimulation, intracellular calcium ([Ca 2+] i) signaling is the upstream of numerous mechanotransduction pathways [4]. We hypothesize that the chondro-protective mechanisms of ZA could be represented by the characteristics of [Ca 2+] i signaling of in situ chondrocytes. Our specific aims were to: (i) compare the in situ spontaneous [Ca 2+] i responses of chondrocytes cultured in non-ZA and ZA supplemented environments, and (ii) compare the biomechanical properties of cartilage allografts under the two culture conditions.

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