Biological Actions Research Articles

Adaptogenic Botanicals with Emphasis on Rhodiola rosea and Withania somnifera

This review addresses the issue of plant adaptogens, botanical products with remarkable anti-stress effects. These actions result from its ability to increase the non-specific organism's resistance process against multiple stressors (physical, chemical or biological). They are capable of exerting a normalizing effect on the human body, being both non-toxic effects and not influencing normal organic functions. Several plants with a complex phytochemical profile meet the criteria for being adaptogens. Many of them have been used in traditional medicine as tonic-vitalizing agents for centuries to treat various health conditions. This review briefly explains the organism's stress responses against stressors and the evolution of the adaptogenic concept from a historic perspective. A rational classification of adaptogens plants is formulated although it does not cover the full variability of botanical adaptogens. Nevertheless, summarizing data from two of the most important plant adaptogens, golden root (Rhodiola rosea) and Indian ginseng (Withania somnifera), are described. This includes their most deserving ethnomedicinal properties, the various families of compounds that constitute their complex phytochemical profiles, pharmacological activities along with putative mechanism of action responsible for some of their multifaceted biological actions, and the multi-therapeutic and health-promoting activities obtained from the most relevant clinical trials performed to date. Additionally, several relevant and current issues regarding the safety and toxicity of both widely used adaptogens are detailed. These include potential negative drugs interactions, putative contraindications and warnings in specific physiological statuses or health conditions. Finally, despite the overlapping activities against stress and stress-related health conditions some superior therapeutic benefits are tentatively assigned both to Withania somnifera and Rhodiola rosea taking into account the overall evidence of efficacy from pharmacological and clinical studies.

USP30 promotes the progression of breast cancer by stabilising Snail

Breast cancer (BC) is the most prevalent tumour in women worldwide. USP30 is a deubiquitinase that has been previously reported to promote tumour progression and lipid synthesis in hepatocellular carcinoma. However, the role of USP30 in breast cancer remains unclear. Therefore, we investigated its biological action and corresponding mechanisms in vitro and in vivo. In our study, we found that USP30 was highly expressed in breast cancer samples and correlated with a poor patient prognosis. Knockdown of USP30 significantly suppressed the proliferation, invasion and migration abilities of BC cells in vitro and tumour growth in vivo, whereas overexpression of USP30 exhibited the opposite effect. Mechanistically, we verified that USP30 interacts with and stabilises Snail to promote its protein expression through deubiquitination by K48-linked polyubiquitin chains and then accelerates the EMT program. More importantly, USP30 reduced the chemosensitivity of BC cells to paclitaxel (PTX). Collectively, these data demonstrate that USP30 promotes the BC cell EMT program by stabilising Snail and attenuating chemosensitivity to PTX and may be a potential therapeutic target in BC.

Snake Venom: A Promising Source of Neurotoxins Targeting Voltage-Gated Potassium Channels.

The venom derived from various sources of snakes represents a vast collection of predominantly protein-based toxins that exhibit a wide range of biological actions, including but not limited to inflammation, pain, cytotoxicity, cardiotoxicity, and neurotoxicity. The venom of a particular snake species is composed of several toxins, while the venoms of around 600 venomous snake species collectively encompass a substantial reservoir of pharmacologically intriguing compounds. Despite extensive research efforts, a significant portion of snake venoms remains uncharacterized. Recent findings have demonstrated the potential application of neurotoxins derived from snake venom in selectively targeting voltage-gated potassium channels (Kv). These neurotoxins include BPTI-Kunitz polypeptides, PLA2 neurotoxins, CRISPs, SVSPs, and various others. This study provides a comprehensive analysis of the existing literature on the significance of Kv channels in various tissues, highlighting their crucial role as proteins susceptible to modulation by diverse snake venoms. These toxins have demonstrated potential as valuable pharmacological resources and research tools for investigating the structural and functional characteristics of Kv channels.

Exploring the Role of Phytochemicals in Arthritic Disorders: A Review

Rheumatoid arthritis (RA) is a prevalent inflammatory condition exemplified by a prolonged course and diverse levels of complexity in symptoms involving joints, extra-articular organs and systemic manifestations, impacting a substantial number of people worldwide. The current treatment regimen of RA involves various synthetic drugs which cause severe side effects and occasionally infections also having high cost and impaired life quality. Plants and herbs contain abundant phytochemicals, which have demonstrated effectiveness in preventing, treating, or alleviating a range of health issues. Phytochemicals due to their low cost, safety and effectiveness in RA treatment and better patient acceptability are used as an alternative therapy. Currently, varied phytochemicals are isolated and evaluated for anti-arthritic drugs as they possess diverse chemical structures and specific biological actions. Phytochemicals are tested as a novel curative approach for arthritis management. In the present review, our intention is to present the role of different phytochemicals in reducing the progression of RA. We also aim to present a mechanism-based reduction of arthritic symptoms

Synergistic Antifungal Bioassay of Neem Leaves Extract with Essential Oils against Dermatophytes

Introduction: The neem plant is also known as a panacea in dentistry due to its antimicrobial properties and plays vital role in the cosmetic industry as it is extensively used in cosmetic preparations for hair and skin care. Objective: The present study was carried out to evaluate the synergistic activity of essential oils in combination with neem leaves ethanolic extracts. Methods: The antifungal activity of neem leaves (Azadirachta indica) ethanolic extracts in combination with A. indica, Eucalyptus citriodora and Cymbopogon martini essential oils was conducted by agar well diffusion method followed by M38-A2 broth microdilution method on pathogenic dermatophytes strains; Microsporum gypseum, Trichophyton mentagrophytes and T. rubrum. Neem leaves extract was obtained by treating the matured green leaves with ethanol. Moreover, HPLC analysis was performed to narrate the terpenoid content having extensively noted antifungal spectrum. The potent antimycotic fluconazole taken as a positive control. Result: The result exhibited that there was overall growth retardation of the dermatophytes at minimum inhibitory concentration between 125 to 250 μg/mL for leaves extract and between 0.078 to 5.0 μL for selected essential oils. The range of minimum inhibitory concentration (MIC) of fluconazole was found between 0.25 and 0.50 μg/mL. Conclusion: Neem leaves ethanolic extracts analysis showed the possible existence of terpenoids in extracts that are recognized having extensive biological action. The outcomes of this study showed a novel report on the therapeutic potential of neem leaves extract with A. indica, E. citriodora and C. martini to control dermatophytosis. The neem leaf extract and antifungal herbal oil in combination have been proven to improve and broad-spectrum antifungal activity and they can be formulated in suitable formulations for the effective treatment of mycosis.

Targeting Mitochondrial ATP-Synthase: Evolving Role of Chromium as a Regulator of Carbohydrate and Fat Metabolism.

The micronutrient trivalent chromium, 3 + (Cr(III)), is postulated to play a role in carbohydrate, lipid, and protein metabolism. Although the mechanisms by which chromium mediates its actions are largely unknown, previous studies have suggested that pharmacological doses of chromium improve cardiometabolic symptoms by augmenting carbohydrate and lipid metabolism. Activation of AMP-activated protein kinase (AMPK) was among the many mechanisms proposed to explain the salutary actions of chromium on carbohydrate metabolism. However, the molecular pathways leading to the activation of AMPK by chromium remained elusive. In an elegant series of studies, Sun and coworkers recently demonstrated that chromium augments AMPK activation by binding to the beta-subunit of ATP synthase and inhibiting its enzymatic activity. This mini-review attempts to trace the evolving understanding of the molecular mechanisms of chromium leading to the hitherto novel pathway unraveled by Sun and coworkers and its potential implication to our understanding of the biological actions of chromium.

Differential Expression of Insulin Growth Factor 1 (IGF-1) Isoforms in Different Types of Endometriosis: Preliminary Results of a Single-Center Study.

Endometriosis is a benign, estrogen-dependent gynecological condition with an uncertain exact pathogenetic mechanism. The aim of this study was to evaluate the potential differential expression of Insulin Growth Factor 1 (IGF-1) isoforms in deeply infiltrating endometriotic (DIE) lesions, in ovarian endometriomas, and in the eutopic endometrium of the same endometriosis patients and to compare their expression with that in the eutopic endometrium of women without endometriosis. A total of 39 patients were included: 28 with endometriosis, of whom 15 had endometriomas only, 7 had DIE nodules only, and 6 had both DIE and endometriomas, and 11 without endometriosis served as controls. We noticed a similar pattern of expression between IGF-1Ea and IGF-1Ec, which differed from that of the IGF-1Eb isoform, possibly implying differential biological actions of different isoforms in DIE subtypes. We observed a tendency of lower expression of IGF-1Ea and IGF-1Ec in endometriomas without DIE compared to endometriomas with concurrent DIE or in DIE nodules. In conclusion, differential expression of IGF-1 isoforms may indicate that DIE with its associated ovarian lesions and simple ovarian endometriosis should be considered as two forms of the disease developing under different molecular pathways.

РОЛЬ СВОБОДНЫХ АМИНОКИСЛОТ В ПОДДЕРЖАНИИ ОСМОТИЧЕСКОГО ГОМЕОСТАЗА У РЫБ

This article is a review of the data presented in literature describing the roles of free amino acids and dipeptides in maintenance of osmotic homeostasis in following groups of lower vertebrates: hagfishes, lampreys, elasmobranchs, sturgeons and bony fishes. The emphasis is made on the role of former metabolites as “compatible osmolytes”. Those are small organic metabolites preserving biological function and native structure of macromolecules such as proteins and nucleic acids under action of high ionic power. Mechanism of this biological action is briefly described. Evolution of the main osmoregulatory strategies in lower vertebrates is briefly considered. The role of amino acids as energy sources helping to cover elevated demands of the organism during osmotic stress and the role of building blocks for synthesis of protein ionic channels, hormones, enzymes etc. participating in salinity coping strategies of the organism are also discussed. Amino acids playing the main role in osmotic adjustments of marine elasmobranchs are: taurine, beta-alanine, sarcosine, followed by glycine, alanine and proline. In freshwater elasmobranchs beta-alanine, taurine, proline, glycine, glutamine and glutamate can be used. In sturgeons main amino acids in osmoregulation can be glycine, beta-alanine, taurine, glutamate, glutamine. Finally, bony fishes use mainly taurine, proline, glycine, alanine, in particular species such as Monopterus albus – glutamine as compatible osmolytes. Bony fishes also use sarcosine, alanine, methionine, glutamate, aspartate as metabolic precursors of amino acid osmolytes. The role of dipeptides such as carnosine, anserine and dipeptide lysine-proline is controversial and requires further investigations.

Bipolar Resistive Switching in 2D MoSe2 Grown by Atmospheric Pressure Chemical Vapor Deposition.

Two-dimensional (2D) transition metal dichalcogenides (TMDCs) are highly promising nanomaterials for various electronic devices such as field-effect transistors, junction diodes, tunneling devices, and, more recently, memristors. 2D MoSe2 stands out for having high electrical conductivity, charge carrier mobility, and melting point. While these features make it particularly appropriate as a switching layer in memristive devices, reliable and scalable production of large-area 2D MoSe2 still represents a challenge. In this study, we manufacture 2D MoSe2 films by atmospheric-pressure chemical vapor deposition and investigate them on the atomic scale. We selected and transferred MoSe2 bilayer to serve as a switching layer between asymmetric Au-Cu electrodes in miniaturized crossbar vertical memristors. The electrochemical metallization devices showed forming-free, bipolar resistive switching at low voltages, with clearly identifiable nonvolatile states. Other than low-power neuromorphic computing, low switching voltages approaching the range of biological action potentials could unlock hybrid biological interfaces.

The effectiveness of feed additives in chronic kidney disease in cats

Chronic kidney disease in cats is one of the most common diseases. The main direction of palliative therapy for chronic kidney disease and extending the survival time of cats is to limit phosphates in the diet and normalize the phosphorus content in the animal’s body. In order to reduce phosphates, phosphate binders are used - substances whose mechanism of action is to bind excess phosphate ions in the gastrointestinal tract, which prevents their entry into the blood-stream. The purpose of the study is to analyze the effectiveness of feed additives “Urdetox” and “Ipakitine” in a comparative aspect in the palliative treatment of chronic kidney disease in cats. Determination of the biological activity of the proposed feed additive for cats with CKD in the form of tablets was carried out on the basis of veterinary clinics in the city. Volgograd, St. Petersburg, Moscow, in the period 2021-2022. The objects of the study were cats whose owners complained of loss of animal body weight, often a general depressed state, decreased appetite, periodic vomiting, frequent urination, dull hair. The diagnosis and experiment were carried out by collecting anamnestic data, determining clinical signs and laboratory data - a general urine test and a biochemical analysis of blood serum. Studies have shown that feed additives containing a phosphate binder and a detoxicant help eliminate the main clinical manifestations of chronic renal failure. The introduction of the essential amino acid -taurine into the feed additive in the form of Urdetox tablets, as well as the accuracy of dosing and ease of use increase the effectiveness of its biological action.

Bioethanol production in bioreactor assisted by magnetic field: Correlation between S. cerevisiae H+ effluxes and fermentative efficiency

This study simultaneously evaluated fermentation kinetics and H+ fluxes during fermentation by Saccharomyces cerevisiae in order to elucidate the biochemical mechanisms behind bioethanol production induced by ELF magnetic fields. Fermentation kinetics were monitored by glucose uptake, ethanol production, secondary products (glycerol), pH, biomass, and biochemical characterization of ATPase activity through proton efflux density measurements.A face-centered central composite design 22 was performed, considering independent variables such as recycling arrangements (bioreactor with a spiral-shaped tube, whole bioreactor, and bioreactor with a U-shaped tube) and magnetic flux density (5, 10, and 15 mT), while alcoholic fermentation efficiency and H+ efflux density of the P-ATPase were the response variables.ELF magnetic fields induced substrate consumption and bioethanol formation in all experimental configurations when compared to fermentations without the field. However, the whole bioreactor exposed to 10 mT was the most attractive condition, resulting in an average increase of approximately 40 % and 18 % in the overall volumetric productivity of glucose consumption and ethanol production, respectively, compared to the control experiment. The effect of magnetic flux density on fermentative efficiency and H+ efflux density was statistically significant (p < 0.1). A direct correlation between H+ efflux and yeast performance during fermentation under magnetic fields was found through the application of a method for simultaneous optimization of the experimental results. The data are discussed in relation to the biological mechanism of action involved and the potential applications of this technology at an industrial scale are envisioned.

Molecular structure, different solvents interaction, thermodynamic, electronic, topological, and chemical behaviors of cis-2,6-dimethylpiperazin- anti depression agent

The Cis-2,6-Dimethylpiperazin has undergone wave function analysis to determine the topological characteristics. The vibrational and ultraviolet-visible spectroscopy investigations were carried out. By advocating Density Functional Theory as a technique, the optimized structure is computed. Polarizability, nucleophilicity, and electrophilicity have also been estimated using Non-Linear Optics, Fukui, and Molecular Electro Static Potential. Additionally, the Highest occupied molecular orbital to Lowest unoccupied molecular orbital studies were carried out to know biological activity. It has been hypothesized that drug-like properties can explain a biological reaction. We predicted and examined the various thermodynamic properties. In addition to previous studies, the docking process was employed to calculate the energies of binding and size of bonding hydrogen with various proteins. This work describes molecular, electrical, chemical, and biological actions.

STRUCTURE AND BIOMEDICAL PROPERTIES OF LIGNINS (REVIEW)

The proposed literature review is in line with current trends in the development of nature-like technologies and is devoted to the analysis of the chemical structure and the search for new ways to use lignins for biomedical applications. Lignins are unique biopolymers of plant origin, the structural organization of which is multivariate and largely depends on the biological species of the plant. Fundamental structural and chemical studies are increasingly clarifying our understanding of the macromolecules structure of this key plant biopolymer, and the study of various taxonomic origins lignins shows to what extent evolution and natural variability have led to a complication of the chemical structure of macromolecules, including through the inclusion of "unconventional" phenolic monomers. This suggests that lignins contain much more structural units than the three monolignol variants described in lignin chemistry textbooks. As a result, as the analysis of the literature data shows, the very definition of lignin continues to expand and refine. Currently, there is a dramatic increase in interest in lignin-based materials, mainly due to their diverse beneficial properties, such as biodegradability, reactivity, biocompatibility, low toxicity and a wide range of biological activity. One of the main objectives of this article is to identify and discuss the mechanisms of biological action of lignins on living organisms to assess the biomedical potential and substantiate the possibility of their use as innovative drugs of antioxidant, radioprotective and geroprotective action. Finding new ways to use lignins is necessary to meet the challenges of maintaining health and improving the quality and duration of people's lives.

Strength and self-healing behavior of bacteria biocomposite concrete in soil exposure condition

The ever-increasing extractive load on hydrocarbon resources, and growing worldwide environmental and social concern have made it necessary to find new material composites in construction that are environment friendly. Natural fibers, they being light weight, bio-renewable, low-cost and eco-friendly is recently used in various industrial applications. Microbiologically induced calcium carbonate precipitation (MICP) by bacteria added in natural fiber is investigated as possible sustainable method for strengthening and repairing cracks in concrete. In this study coir, flax, and jute fibers are used as carriers for bacterial spores to promote strength enhancement and self-healing in concrete. Bacillus tropicus added along with aforementioned natural fibers in concrete by direct addition and immobilization to determine the compressive strength, compressive strength regain and ultrasonic pulse velocity test and crack healing characteristics in concrete. Artificial cracks are induced in Bacteria Biocomposite Concrete Specimens (BBCS) to width of 0.5–1 mm and healing efficiency is determined for soil exposure condition for a period of 56 days. Bacteria added by immobilization and direct addition rendered 79.71 % and 64.49 % of enhanced healing efficiency respectively. Microstructure studies on BBCS and crack filling material (white precipitate) reveals the presence of calcium carbonate compounds, which is due to biological action of bacteria in concrete and exposure environment.

The influence of calcitriol on indicators of apoptosis, inflammation and oxidative stress in the myocardium of rats under conditions of modulation of the hydrogen sulfide / cystathionine-gamma-lyase system

Annotation. Vitamin D plays an important role in the control of the cardiovascular system, including myocardial remodeling and hypertrophy. Hydrogen sulfide (H2S) is an important mediator of cardiomyocyte adaptive mechanisms to stress factors. The role of the H2S system in the mechanisms of biological action of vitamin D in the cardiovascular system has not been clarified. The aim of the work was to determine the effect of the active form of vitamin D - calcitriol on the indicators of apoptosis, inflammation and oxidative stress in the myocardium of rats under conditions of modulation of the H2S / cystathionine-γ-lyase system. The experiments were performed on 90 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986). Over a period of 4 weeks, 6 groups of animals were administered 1,25 (OH)2D3 at doses of 0.1 and 1 μg/kg. To modulate the H2S system, propargylglycine (PPG) and NaHS were administered. The H2S content, markers of inflammation, apoptosis, and oxidative stress were determined in the myocardium. Statistical analysis was performed using the IBM Statistics SPSS 26 software package. It was established that 1,25 (OH)2D3 in a dose of 0.1 μg/kg increases the level of H2S in the myocardium, while at a dose of 1 μg/kg it has an inhibitory effect on the H2S system. Modulators of H2S exchange modify pathochemical changes in the myocardium induced by 1,25 (OH)2D3 at a dose of 1 μg/kg. PPG potentiates the increase in the levels of mediators of inflammation and apoptosis, deepens the imbalance in the system of heat shock proteins and signs of oxidative stress. Administration of NaHS does not cause significant changes in myocardial parameters under the influence of a physiological dose of 1.25 (OH)2D3 and significantly reduces the pro-apoptotic and pro-inflammatory effects of a high dose of 1.25 (OH)2D3.

Green Synthesis of New Heterocyclic Surfactant Compounds by Multicomponent Reactions and Their Antibacterial and Corrosion Inhibitor, Study on Carbon Steel Alloy in Acid Media 2 M HCl

Heterocyclic 1,4-di(1,3,5-dithiazinan-5-yl)benzene (D) and two heterocyclic-cationic Gemini surfactant 5,5'-(1,4-phenylene)bis(5-decyl-1,3,5-dithiazinan-5-ium)bromide (E) and 5,5'-(1,4-phenylene)bis(5-tetradecyl-1,3,5-dithiazinan-5-ium)bromide (F) were prepared and identified by FTIR, 1H-NMR spectroscopies, and GC–MS. Then, they were tested as corrosion inhibitors against carbon steel corrosion in 2.0 M aggressive HCl medium at 25 and 50 °C. They have different carbon chain tails, i.e., E (10 carbons), and F (14 carbons). These new heterocyclic and surfactant categories as corrosion inhibitors. The corrosion process has been studied electrochemically (Tafel Plot). The inhibition efficiency clarified that the decrease in IE(%) is in the order of F &gt; E &gt; D. The biological activity of compounds D and F was investigated using the aforementioned drilling procedure with a cork drill. At a dosage of 3000 mcg/mL, the biological action of compound D demonstrated effective resistance against the two types of negative bacteria. The cation has a diameter of 20 mm against E. coli and 19 mm against S. epidermis bacteria. At the same concentration, the chemical F is solely effective against E. coli with an inhibition diameter of 14 mm.

Vibrational Spectroscopic, 13C NMR, DFT Studies on Chlorofullerene (C60Cl6): A Potential Bioactive Agent

Abstract. The present work comprises the systematic computational chemical findings on Chlorofullerene (C60Cl6). The molecular structure of C60Cl6 was optimized by density function theory (DFT)/B3LYP model of 6-31G(d,p) basis set using Gaussian 09 program. The infrared and Raman spectra were simulated and assigned for C60Cl6 molecule. Carbon – chlorine stretching vibrations are found to be in the range 150-900 cm-1 and the chains are strongly affected with the radial vibrations of the carbon sphere. The optimized geometries at ground-state of the molecules are calculated without any geometrical restriction, except those enforced by symmetry and the molecules are found to be minima on their respective potential energy surfaces. The optimized structures have been subjected to Gauge including atomic orbital (GIAO), the chemical shielding tensors using B3LYP/6-31G(d,p) in solvent phase with the aim of calculating 13C chemical shift values with respect to trimethylsilane (TMS) as computational reference. Molecular acuteness and stability were investigated using the Frontier molecular orbitals (FMO) analysis. The molecular electrostatic potential (MEP) mapping provides a valuable information regarding the net electrostatic effect produced by net charge distribution of the molecule. Chlorofullerenes are considered to be promising compounds for the investigation of biological action which show pronounced anti-HIV action and low toxicity. Hence, these results set goal in scheming the biocompatible molecules which will be useful in the field of carbon nano medicine and drug delivery application.

In Vivo Wound Healing in Drosophila melanogaster and Mouse Models: Synergistic Effect of Bovine Serum Albumin and Graphene Quantum Dots.

Bovine serum albumin (BSA)-based biomaterials have garnered significant attention for their remarkable potential in wound healing, primarily due to their effective biological actions in addressing the skin inflammation phase and mitigating hypoalbuminemia. Motivated by these attributes, a nanocomposite hydrogel is developed by blending BSA with poly(vinyl alcohol) (PVA), complemented by the incorporation of graphene quantum dot (GQD). The FTIR study establishes a hydrogen-bonding interaction between the -NH2 groups of BSA and the -OH group of PVA. Microscopic investigations establish that the dispersion of GQDs with an average size of 22.5 nm results in smoothening of the surface of the nanocomposite. The nanocomposite hydrogel reveals excellent swelling attributes of about 920% in a period of 6 h due to its optimum cross-linking condition. Furthermore, the hydrogel exhibits a water vapor transmission rate of 8.45 mg cm-2 h-1, akin to the transmission rate of wounded skin. The PVA/BSA@GQD nanocomposite's antibacterial efficacy is evaluated against Morganella morganii bacteria, showing 99% killing, while its cytotoxicity assay against HeLa cells exhibited a minimum cell viability of 76% at a 20 μM concentration, which is ideal for a wound dressing material. In vivo wound healing investigations are conducted on Drosophila, showcasing a 100% wound surface closure within 4 h. This outcome is further substantiated through in vivo studies involving mice, where complete re-epithelialization is achieved within a span of 13 days. The combined results establish the PVA/BSA@GQD nanocomposite as a potential wound dressing material.

Surface defect engineered-Mg-based implants enable the dual functions of superhydrophobic and synergetic photothermal/chemodynamic therapy.

Promoting metallic magnesium (Mg)-based implants to treat bone diseases in clinics, such as osteosarcoma and bacterial infection, remains a challenging topic. Herein, an iron hydroxide-based composite coating with a two-stage nanosheet-like structure was fabricated on Mg alloy, and this was followed by a thermal reduction treatment to break some of the surface Fe-OH bonds. The coating demonstrated three positive changes in properties due to the defects. First, the removal of -OH made the coating superhydrophobic, and it had self-cleaning and antifouling properties. This is beneficial for keeping the implants clean and for anti-corrosion before implantation into the human body. Furthermore, the superhydrophobicity could be removed by immersing the implant in a 75% ethanol solution, to further facilitate biological action during service. Second, the color of the coating changed from yellow to brown-black, leading to an increase in the light absorption, which resulted in an excellent photothermal effect. Third, the defects increased the Fe2+ content in the coating and highly improved peroxidase activity. Thus, the defect coating exhibited synergistic photothermal/chemodynamic therapeutic effects for bacteria and tumors. Moreover, the coating substantially enhanced the anti-corrosion and biocompatibility of the Mg alloys. Therefore, this study offers a novel multi-functional Mg-based implant for osteosarcoma therapy.

Development of Dual Inhibitors of Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase with Tetrazole Core.

The attractive biological actions of the eicosatrienoic acids (EETs) and endocannabinoids (eCBs) are terminated by means of enzymatic hydrolysis via soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) enzymes. Simultaneous inhibition of both enzymes is considered a novel approach in the treatment of inflammatory and neuropathic pain. In this study, a novel series of tetrazole derivatives as dual sEH/FAAH inhibitors were designed, synthesized, and biologically evaluated. Compounds 6c, 7d, and 8a, the most potent inhibitors against FAAH and sEH enzymes with acceptable IC50 values, significantly decreased carrageenan- induced paw edema 5h after carrageenan injection compared to the control group compound. In addition, compound 7d exhibited a significant reduction in pain scores compared to the control group. Docking studies showed that the presented dual inhibitors could bind to the essential residues in the catalytic sites of both enzymes. In silico prediction of several pharmacokinetic properties suggests that these dual inhibitors could potentially be orally active agents. These structures will be a valuable scaffold to develop soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.