Corrigendum: Three naturally-occurring psychedelics and their significance in the treatment of mental health disorders.

[This corrects the article DOI: 10.3389/fphar.2022.927984.].

Three Naturally-Occurring Psychedelics and Their Significance in the Treatment of Mental Health Disorders.

Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.

Ga2O3(Sn) Oxides for High-Temperature Gas Sensors.

Gallium(III) oxide is a promising functional wide-gap semiconductor for high temperature gas sensors of the resistive type. Doping of Ga2O3 with tin improves material conductivity and leads to the complicated influence on phase content, microstructure, adsorption sites, donor centers and, as a result, gas sensor properties. In this work, Ga2O3 and Ga2O3(Sn) samples with tin content of 0-13 at.% prepared by aqueous co-precipitation method were investigated by X-ray diffraction, nitrogen adsorption isotherms, X-ray photoelectron spectroscopy, infrared spectroscopy and probe molecule techniques. The introduction of tin leads to a decrease in the average crystallite size, increase in the temperature of ß-Ga2O3 formation. The sensor responses of all Ga2O3(Sn) samples to CO and NH3 have non-monotonous character depending on Sn content due to the following factors: the formation of donor centers and the change of free electron concentration, increase in reactive chemisorbed oxygen ions concentration, formation of metastable Ga2O3 phases and segregation of SnO2 on the surface of Ga2O3(Sn) grains.

Synthesis and biological activity of 5-aryliden-2-thiohydantoin S-aryl derivatives.

Three new and complementary approaches to S-arylation of 2-thiohydantoins have been developed: copper-catalyzed cross coupling with either arylboronic acids or aryl iodides under mild conditions, or direct nucleophilic substitution in activated aryl halides. For 38 diverse compounds, reaction yields for all three methods have been determined. Selected by molecular docking, they have been tested on androgen receptor activation, and p53-Mdm2 regulation, and A549, MCF7, VA13, HEK293T, PC3, LnCAP cell lines for cytotoxicity, Two of them turned out to be promising as androgen receptor activators (likely by allosteric regulation), and another one is shown to activate the p53 cascade. It is hoped that 2-thiohydantoin S-arylidenes are worth further studies as biologically active compounds.

Synthesis of Inorganic Pyrophosphatase-Nanodiamond Conjugates Resistant to Calcium and Fluoride.

Pyrophosphate arthropathy is the mineralization defect in humans caused by the deposition of microcrystals of calcium pyrophosphate dihydrate in joint tissues. As a potential therapeutic strategy for the treatment of pyrophosphate arthropathy, delivery of exogenous pyrophosphate-hydrolyzing enzymes, inorganic pyrophosphatases (PPases), to the synovial fluid has been suggested. Previously, we synthesized the conjugates of Escherichia coli PPase (Ec-PPase) with detonation synthesis nanodiamonds (NDs) as a delivery platform, obtaining the hybrid biomaterial retaining high pyrophosphate-hydrolyzing activity in vitro. However, most known PPases including Ec-PPase in the soluble form are strongly inhibited by Ca2+ ions. Because synovial fluid contains up to millimolar concentrations of soluble calcium, this inhibition might limit the in vivo application of Ec-PPase-based material in joint tissues. In this work, we proposed other bacterial PPases from Mycobacterium tuberculosis (Mt-PPase), which are resistant to the inhibition by Ca2+ ions, as an active PPi-hydrolyzing agent. We synthesized conjugates of Mt-PPase with NDs and tested their activity under various conditions. Unexpectedly, conjugates of both Ec-PPase and Mt-PPase with aminated NDs retained significant hydrolytic activity in the presence of well-known mechanism-based PPase inhibitors, fluoride or calcium. The incomplete inhibition of PPases by fluoride or calcium was found for the first time.

Aging Biomarkers: From Functional Tests to Multi-Omics Approaches.

Aging results in various deleterious changes in the human body that may lead to loss of function and the manifestation of chronic diseases. While diseases can generally be reliably diagnosed, the aging process itself requires more sophisticated approaches to evaluate its progression. Numerous attempts have been made to establish biomarkers to quantify human aging at the cellular, tissue, and organismal level. Here, an up-to-date overview of biomarkers related to human aging with an emphasis on biomarkers that take into account different mechanisms of aging between individuals is provided. Classical discrete molecular and non-molecular biomarkers handpicked by researches on the base of their strong correlation with age, as well as emerging omics-based biomarkers, are discussed and potential future directions and developments in the field of aging assessment are outlined.

Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA.

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), has recently emerged as a prominent biomarker of prostate cancer (PC) and as an attractive protein trap for drug targeting. At the present time, several drugs and molecular diagnostic tools conjugated with selective PSMA ligands are actively evaluated in different preclinical and clinical trials. In the current work, we discuss design, synthesis and a preliminary biological evaluation of PSMA-specific small-molecule carrier equipped by Doxorubicin (Dox). We have introduced an unstable azo-linker between Dox and the carrier hence the designed compound does release the active substance inside cancer cells thereby providing a relatively high Dox concentration in nuclei and a relevant cytotoxic effect. In contrast, we have also synthesized a similar conjugate with a stable amide linker and it did not release the drug at all. This compound was predominantly accumulated in cytoplasm and did not cause cell death. Preliminary in vivo evaluation has showed good efficiency for the degradable conjugate against PC3-PIP(PSMA+)-containing xenograft mine. Thus, we have demonstrated that the conjugate can be used as a template to design novel analogues with improved targeting, anticancer activity and lower rate of potential side effects. 3D molecular docking study has also been performed to elucidate the underlying mechanism of binding and to further optimization of the linker area for improving the target affinity.

Stereocontrolled [3+2] Cycloaddition of Donor-Acceptor Cyclopropanes to Iminooxindoles: Access to Spiro[oxindole-3,2'-pyrrolidines].

A novel stereocontrolled assembly of spiro[oxindole-3,2'-pyrrolidines] via [3+2]-cycloaddition of donor-acceptor cyclopropanes to electron-poor ketimines, iminooxindoles, was developed. The method allows for efficient employment of common readily available donor-acceptor cyclopropanes, functionalized with ester, keto, nitro, cyano etc. groups, and N-unprotected iminooxindoles. The stereospecificity of the initial SN2-like imine attack on a cyclopropane molecule together with a high diastereoselectivity of further C-C bond formation facilitate a rapid access to spiro[oxindole-3,2'-pyrrolidines] in their optically active forms. Preliminary in vitro testing of the synthesized compounds against LNCaP (p53+) and PC-3 (p53-) cells revealed good antiproliferative activities and p53-selectivity indices for several compounds that are intriguing in terms of their further investigation as inhibitors of MDM2-p53 interaction.

Precise relative-quantity judgement in the striped field mouse Apodemus agrarius Pallas.

Applying the classical experimental scheme of training animals with food rewards to discriminate between quantities of visual stimuli, we demonstrated that not only can striped field mice Apodemus agrarius discriminate between clearly distinctive quantities such as 5 and 10, but some of these mice also exhibit high accuracy in discriminating between quantities that differ only by one. The latter include both small (such as 2 versus 3) and relatively large (such as 5 versus 6, and 8 versus 9) quantities of elements. This is the first evidence of precise relative-quantity judgement in wild rodents. We found striking individual variation in cognitive performance among striped field mice, which possibly reflects individual cognitive variation in natural populations. We speculate that high accuracy in differentiating large quantities is based on the adaptive ability of wild rodents to capture subtle changes in their environment. We suggest that the striped field mouse may be a powerful model species to develop advanced cognitive tests for comparative studies of numerical competence in animals and for understanding evolutionary roots of quantity processing.

3-(2-Azidoethyl)oxindoles: Advanced Building Blocks for One-Pot Assembly of Spiro[pyrrolidine-3,3'-oxindoles].

A new synthetic approach to biologically relevant spiro[pyrrolidine-3,3'-oxindoles] was developed on the basis of the cascade transformation of 3-(2-azidoethyl)oxindoles via Staudinger/aza-Wittig/Mannich reactions. The parent azides were readily synthesized through a nucleophilic ring opening of spiro[cyclopropane-1,3'-oxindoles] with the azide ion. A series of new spiro[pyrrolidine-3,3'-oxindoles] with various (het)aryl substituents at the C2 and C5 positions of the pyrrolidine ring were synthesized. In vitro experiments revealed their high cytotoxicity toward LNCaP and PC-3 tumor cell lines.

Immobilization of inorganic pyrophosphatase on nanodiamond particles retaining its high enzymatic activity.

Nanodiamond (ND) particles are popular platforms for the immobilization of molecular species. In the present research, enzyme Escherichia coli inorganic pyrophosphatase (PPase) was immobilized on detonation ND through covalent or noncovalent bonding and its enzymatic activity was characterized. Factors affecting adsorption of PPase such as ND size and surface chemistry were studied. The obtained material is a submicron size association of ND particles and protein molecules in approximately equal amounts. Both covalently and noncovalently immobilized PPase retains a significant enzymatic activity (up to 95% of its soluble form) as well as thermostability. The obtained hybrid material has a very high enzyme loading capacity (∼1 mg mg(-1)) and may be considered as a promising delivery system of biologically active proteinaceous substances, particularly in the treatment of diseases such as calcium pyrophosphate crystal deposition disease and related pathologies. They can also be used as recoverable heterogeneous catalysts in the traditional uses of PPase.