Biochemical Modification of Titanium Oral Implants: Evidence from In Vivo Studies

The discovery of osseointegration of titanium implants revolutionized the dental prosthesis field. Traditionally, implants have a surface that is processed by additive or subtractive techniques, which have positive effects on the osseointegration process by altering the topography. In the last decade, innovative implant surfaces have been developed, on which biologically active molecules have been immobilized with the aim of increasing stimulation at the implant–biological tissue interface, thus favoring the quality of osseointegration. Among these molecules, some are normally present in the human body, and the techniques for the immobilization of these molecules on the implant surface have been called Biochemical Modification of Titanium Surfaces (BMTiS). Different techniques have been described in order to immobilize those biomolecules on titanium implant surfaces. The aim of the present paper is to present evidence, available from in vivo studies, about the effects of biochemical modification of titanium oral implants on osseointegration.

Silent control: microbial plant pathogens evade host immunity without coding sequence changes

ABSTRACT Both animals and plants have evolved a robust immune system to surveil and defeat invading pathogenic microbes. Evasion of host immune surveillance is the key for pathogens to initiate successful infection. To evade the host immunity, plant pathogens evolved a variety of strategies such as masking themselves from host immune recognitions, blocking immune signaling transductions, reprogramming immune responses and adapting to immune microenvironmental changes. Gain of new virulence genes, sequence and structural variations enables plant pathogens to evade host immunity through changes in the genetic code. However, recent discoveries demonstrated that variations at the transcriptional, post-transcriptional, post-translational and glycome level enable pathogens to cope with the host immune system without coding sequence changes. The biochemical modification of pathogen associated molecular patterns and silencing of effector genes emerged as potent ways for pathogens to hide from host recognition. Altered processing in mRNA activities provide pathogens with resilience to microenvironment changes. Importantly, these hiding variants are directly or indirectly modulated by catalytic enzymes or enzymatic complexes and cannot be revealed by classical genomics alone. Unveiling these novel host evasion mechanisms in plant pathogens enables us to better understand the nature of plant disease and pinpoints strategies for rational diseases management in global food protection.

Mechanistic insights into volatile anesthetic modulation of K2P channels

K2P potassium channels are known to be modulated by volatile anesthetic (VA) drugs and play important roles in clinically relevant effects that accompany general anesthesia. Here, we utilize a photoaffinity analog of the VA isoflurane to identify a VA-binding site in the TREK1 K2P channel. The functional importance of the identified site was validated by mutagenesis and biochemical modification. Molecular dynamics simulations of TREK1 in the presence of VA found multiple neighboring residues on TREK1 TM2, TM3, and TM4 that contribute to anesthetic binding. The identified VA-binding region contains residues that play roles in the mechanisms by which heat, mechanical stretch, and pharmacological modulators alter TREK1 channel activity and overlaps with positions found to modulate TASK K2P channel VA sensitivity. Our findings define molecular contacts that mediate VA binding to TREK1 channels and suggest a mechanistic basis to explain how K2P channels are modulated by VAs.

A summary of drugs targeting enzymes

Enzymes act as biological catalysts in living organisms, by regulating the rate of chemical reactions, without themselves being altered in the process. Enzymes act as a target for drugs for the desired therapeutic effect, which are thereby called biological targets. Enzymes offer unique opportunities for drug design that are not available to cell surface receptors, nuclear hormone receptors, ion channels, transporters. Drugs that function as enzyme inhibitors constitute a significant portion of the orally bioavailable therapeutic agents that are in clinical use today. Likewise, much of drug discovery and development efforts at present are focused on identifying and optimizing drug candidates that act through inhibition of specific enzyme targets. Drugs acting on enzymes can either inhibit them or activate them. Inhibition of enzymes is a strategy which is more commonly used rather than activation of enzymes. 47% of all current drugs inhibit their enzyme targets. Enzyme activity can not only be inhibited; it can also be accelerated through biochemical modification of the enzyme. In this manuscript, the authors provide a system-wise summary of drugs acting on enzymes, microsomal enzymes targeted by drug and newly approved drugs acting on enzymes.

Protective Effect of Costus Speciosus Rhizome Extract Against Cytotoxicity Induced by Tramadol in Mice

Tramadol is a centrally acting analgesic generally used to treat moderate to severe pain. This study was designed to evaluate the protective effect of Costus speciosus rhizome extract (CSRE) against the chromosomal ’aberration’s tramadol-induced in mice bone marrow. Sixty male albino mice were examined in this study and separated into four groups which are as follows: Control group; CSRE group (which have been supplied with 200 mg/kg per day); Tramadol group (Supplied with 40 mg/kg); and CSRE + Tramadol group ( which were given Tramadol for a period of 4 weeks and then given CSRE for a further 4 weeks, applying the same dosage. Microscopic examination of the bone marrow showed a significant increase in structural chromosomal aberrations (centromeric attenuation, gap chromosome, ring chromosome, end to end association, and centric fusion) in addition to numerical chromosomal aberrations (polyploidy and endomitosis) in the treated mice with Tramadol comparable to mice in the control group. The administration of Tramadol disrupted oxidants-antioxidants balance, which is proven by the increased malondialdehyde (MDA) and the reduced superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Interestingly, in contrast, CSRE administration has shown attenuate in the numerical chromosomal aberrations and biochemical modification caused by Tramadol. This study demonstrated that CSRE supplementation is improved the tramadol-induced cytotoxicity injury through its antioxidant activity.

Unlocking the power of fatty acids as dietary tracers and metabolic signals in fishes and aquatic invertebrates

Determining the transfer and transformation of organic matter in food webs is a fundamental challenge that has implications for sustainable management of ecosystems. Fatty acids (FA) offer a potential approach for resolving complex diet mixtures of organisms because they provide a suite of molecular tracers. Yet, uncertainties in the degree of their biochemical modification by consumers, due to selective retention or metabolism, have limited their application. Here, we consolidated 316 controlled feeding studies of aquatic ectotherms (fishes and invertebrates) involving 1404 species–diet combinations to assess the degree of trophic modification of FA in muscle tissue. We found a high degree of variability within and among taxa in the %FA in consumer muscle tissue versus %FA in diet regression equations. Most saturated FA had weak relationships with the diet ( r 2 < 0.30) and shallow slopes ( m < 0.30), suggesting a lack of retention in muscle when fed in increasing amounts. Contrarily, several essential FA, including linoleic (18:2n-6) and α-linolenic acid (18:3n-3), exhibited significant relationships with the diet ( m > 0.35, r 2 > 0.50), suggesting supply limitations and selective retention in muscle by consumers. For all FA, relationships strengthened with increasing taxonomic specificity. We also demonstrated the utility of new correction equations by calculating the potential contributions of approximately 20 prey items to the diet of selected species of generalist fishes using a FA mixing model. Our analyses further reveal how a broad range of fishes and invertebrates convert or store these compounds in muscle tissue to meet physiological needs and point to their power in resolving complex diets in aquatic food webs. This article is part of the theme issue ‘The next horizons for lipids as ‘trophic biomarkers’: evidence and significance of consumer modification of dietary fatty acids’.

Mechanistic insights into volatile anesthetic modulation of K2P channels

K2P potassium channels are known to be modulated by volatile anesthetic (VA) drugs and play important roles in clinically relevant effects that accompany general anesthesia. Here, we utilize a photoaffinity analog of the VA isoflurane to identify a VA binding site in the TREK1 K2P channel. The functional importance of the identified site was validated by mutagenesis and biochemical modification. Molecular dynamic simulations of TREK1 in the presence of VA found multiple neighboring residues on TREK1 TM2, TM3 and TM4 that contribute to anesthetic binding. The identified VA binding region contains residues that play roles in the mechanisms by which heat, mechanical stretch, and pharmacological modulators alter TREK1 channel activity and overlaps with positions found to modulate TASK K2P channel VA sensitivity. Our findings define molecular contacts that mediate VA binding to TREK1 channels and suggest a mechanistic basis to explain how K2P channels are modulated by VAs.

Domain I of β2GPI is capable of blocking serum IgA antiphospholipid antibodies binding in vitro: an effect enhanced by PEGylation

Objectives This study aims to inhibit antiphospholipid syndrome (APS) serum derived IgA anti-beta-2-glycoprotein I (aβ2GPI) binding using Domain I (DI). Methods Serum from 13 APS patients was tested for IgA aβ2GPI and Anti-Domain I. Whole IgA was purified by peptide M affinity chromatography from positive serum samples. Serum was tested for IgA aβ2GPI binding in the presence and absence of either DI or of two biochemically modified variants containing either 20 kDa of poly(ethylene glycol) (PEG) or 40 kDa of PEG. Results Significant inhibition with DI was possible with average inhibition of 23% ( N = 13). Further inhibitions using 20 kDa PEG-DI and 40 kDa PEG-DI variants showed significant inhibition ( p = 0.0001) with both the 40 kDa PEG-DI and 20 kDa PEG-DI variants showing increased inhibition compared with DI alone ( p = 0.0001 and p = 0.001, n = 10). Conclusions Inhibition of IgA aβ2GPI by DI is possible and can be enhanced by biochemical modification in a subset of patients.