Alternative Agents Research Articles

Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment.

Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies.

Use of coconut sugar as an alternative agent in osmotic dehydration of strawberries.

This study aimed to evaluate coconut sugar (CS) as an alternative osmotic agent to sucrose for the osmotic dehydration (OD) of strawberries. OD was performed by immersing strawberries cut into 13.6±0.4mm edge cubes in osmotic solutions of CS or sucrose, at two different concentrations (40% and 60%, w/w), with and without application of vacuum (AV) in the first 20min of the process. The total OD time was 300min. Evaluations of the kinetics of solid gain (SG), water loss (WL), and weight reduction (WR) were performed at 30, 60, 120, 180, 240, and 300min. SG, WL, and WR increased over the OD time and showed values of up to 7.94%, 63.40%, and 55.94%, respectively. AV increased WL, WR, shrinkage, pH, and total color difference and decreased anthocyanin, ascorbic acid (AA), phenolic, and antioxidant contents. The higher concentration led to higher SG, WL, WR, shrinkage, hardness, and lower moisture content, water activity, anthocyanin, AA, phenolic, and antioxidant contents. The use of CS instead of sucrose had little influence on strawberry properties, except pH and color responses. The optimal treatment was using a 60% CS solution without AV, showing a very distinct color change, hardness increased by approximately 4.5 times and maintenance of acidity, anthocyanins, AA, total phenolics, and antioxidants of 38.0%, 39.6%, 11.8%, 30.0%, 31.1%, and 30.3%, respectively, compared to fresh strawberries. PRACTICAL APPLICATION: Osmotic dehydration of fruit is a process traditionally carried out using sucrose. However, increasing health concerns have made consumers seek alternative sugars to sucrose. The use of coconut sugar made it possible to produce osmo-dehydrated strawberries different from the traditional one, maintaining product quality and process efficiency.

Assessment of some physical measures as safe and environmentally friendly alternative control agents for some common coleopteran insects in stored wheat products

Assessment of some physical measures as safe and environmentally friendly alternative control agents for some common coleopteran insects in stored wheat products

In Silico Studies, Design and Synthesis of Novel Fused Pyrimidine Derivatives as a DNA Gyrase Inhibitor and Antibacterial Activity Against Quinolone Resistant Escherichia Coli

In recent years, antimicrobial agents have been crucial in improving public health worldwide. However, due to improper usage, bacteria have developed resistance to these agents. This has led researchers to explore the use of heterocyclic compounds as alternative antimicrobial agents to combat resistance. Considering the success of heterocyclic derivatives in developing effective antimicrobial drugs, we conducted a 2D-QSAR (QSAR models using 2D-descriptors) study on novel pyrimidine derivatives and performed in silico simulations to evaluate their potential antibacterial activity against quinolone-resistant Escherichia coli. We used QSARINS V.2.2 (Insubria) software for the 2D-QSAR analysis and performed in silico absorption, distribution, metabolism, and excretion (ADME) and docking studies on 16 newly designed compounds. The best QSAR model had a high correlation coefficient ([Formula: see text], [Formula: see text], [Formula: see text]) and showed no outliers. Based on these favorable results, we designed 16 new compounds and predicted their antibacterial activity using the best equation. Amongst the top six designed compounds, which had the best docking scores were subjected to practical synthesis. Compound 3cd was found to be good candidature from in-vitro anti-E. Coli activity. This compound may be targeting the DNA gyrases and thus, have inhibitory activity against E. Coli. This observation was also supported by 100[Formula: see text]ns molecular dynamics and normal mode analysis results. The most promising compounds identified through these computational studies may be synthesized and tested as potential new drug candidates for treating bacterial infections.

Inhibitory activity of Limosilactobacillus reuteri isolated from camel milk against Helicobacter pylori effects in human gastric epithelial cells.

This study aimed to evaluate anti-Helicobacter pylori effects of Limosilactobacillus reuteri 2892 (L. reuteri 2892) isolated from camel milk in GC cell lines (AGS and MKN). From 15 camel milk samples, 132 microbial strains were isolated. Based on microbial and biochemical analysis, 11 potential probiotic candidates were selected. The potential probiotic candidates were assayed for anti-H. pylori activity, and the strain with the highest anti-H. pylori activity was identified genotypically. Based on 16S rDNA sequencing, the selected strain with the best activity against H. pylori (inhibition zone=15.5±0.8) belonged to the Lactobacillus reuteri strain 2892. Cell treatment with H. pylori HC-113 inhibits gene expression of Claudin-4, ZO-1, MUC5AC, and MUC2 in gastric cells, which are attenuated by L. reuteri 2892. The simulative effects of H. pylori HC-113 on the cell migration and invasion of gastric cells were lost when cells were cotreated with L. reuteri 2892. Cell treatment with H. pylori HC-113 promoted cell death, whereas cotreatment with L. reuteri 2892 markedly decreased necrotic and late apoptotic cells. The present study demonstrates that L. reuteri 2892 has potent anti-H. pylori effects and thus can be considered as an alternative protective agent against inflammatory effects of H. pylori in gastric cells.

Can Moringa oleifera Leaf Ethyl Acetate Extract Inhibit Candida albicans Planktonic Cell Growth and Biofilm Formation In Vitro?

Introduction: Candida albicans (C. albicans) is the most common fungus found in the human oral cavity. This fungus has the ability to form a biofilm that causes infectious diseases in the oral cavity. Nowadays, the incidence of infectious diseases caused by C.albicans was increasing due to resistance to antifungal drugs. This study aimed to investigate the effect of Moringa oleifera ethyl acetate extract on the inhibition of C. albicans planktonic cell growth and biofilm formation in vitro. Methods: C. albicans (ATCC 10231) was the fungus used in this study. Determination of inhibition planktonic cell growth by microdilution method. The polystyrene microplate assay method was used to test the inhibition of C. albicans biofilm formation. The extract concentrations used in this study were 25%, 12.5%, 6.25%, 3.13%, and 1.57%, respectively. A crystal violet (CV) assay assessed the biofilm's inhibitory activity. Results: The minimal inhibitory concentration of Moringa oleifera leaf ethyl acetate extract against the planktonic form of C.albicans was found to be 1.57%. Starting at 6.25% concentration, Moringa leaf ethyl acetate extract inhibits the formation of C. albicans biofilm. Conclusion: Since Moringa oleifera leaf ethyl acetate extract inhibits C. albicans planktonic and biofilm formation, it has the potential to be developed as an alternative anti-fungal agent.
 Keywords: Moringa leaf extract, planktonic cells, biofilm, Candida albicans

Antimicrobial peptides from Bacillus spp. and strategies to enhance their yield.

Antibiotic resistance is a growing concern that is affecting public health globally. The search for alternative antimicrobial agents has become increasingly important. Antimicrobial peptides (AMPs) produced by Bacillus spp. have emerged as a promising alternative to antibiotics, due to their broad-spectrum antimicrobial activity against resistant pathogens. In this review, we provide an overview of Bacillus-derived AMPs, including their classification into ribosomal (bacteriocins) and non-ribosomal peptides (lipopeptides and polyketides). Additionally, we delve into the molecular mechanisms of AMP production and describe the key biosynthetic gene clusters involved. Despite their potential, the low yield of AMPs produced under normal laboratory conditions remains a challenge to large-scale production. This review thus concludes with a comprehensive summary of recent studies aimed at enhancing the productivity of Bacillus-derived AMPs. In addition to medium optimization and genetic manipulation, various molecular strategies have been explored to increase the production of recombinant antimicrobial peptides (AMPs). These include the selection of appropriate expression systems, the engineering of expression promoters, and metabolic engineering. Bacillus-derived AMPs offer great potential as alternative antimicrobial agents, and this review provides valuable insights on the strategies to enhance their production yield, which may have significant implications for combating antibiotic resistance. KEY POINTS: • Bacillus-derived AMP is a potential alternative therapy for resistant pathogens • Bacillus produces two main classes of AMPs: ribosomal and non-ribosomal peptides • AMP yield can be enhanced using culture optimization and molecular approaches.

Recent Advancements in Pathogenic Mechanisms, Applications and Strategies for Entomopathogenic Fungi in Mosquito Biocontrol.

Fungal diseases are widespread among insects and play a crucial role in naturally regulating insect populations. Mosquitoes, known as vectors for numerous infectious diseases, pose a significant threat to human health. Entomopathogenic fungi (EPF) have emerged as highly promising alternative agents to chemical mosquitocides for controlling mosquitoes at all stages of their life cycle due to their unique infection pathway through direct contact with the insect's cuticle. In recent years, significant advancements have been made in understanding the infection pathways and pathogenic mechanisms of EPF against mosquitoes. Various strategies involving the use of EPF alone or combinations with other approaches have been employed to target mosquitoes at various developmental stages. Moreover, the application of genetic technologies in fungi has opened up new avenues for enhancing the mosquitocidal efficacy of EPF. This review presents a comprehensive summary of recent advancements in our understanding the pathogenic mechanisms of EPF, their applications in mosquito management, and the combination of EPF with other approaches and employment of transgenic technologies. The biosafety concerns associated with their use and the corresponding approaches are also discussed. The recent progress suggests that EPF have the potential to serve as a future biorational tool for controlling mosquito vectors.

Holistic valorization of fayalitic slag to pig iron and glass fibers

A valorization process for fayalitic copper slags is presented. A primary copper slag is reduced via carbothermic reduction thus creating a pig iron phase and a secondary copper slag, which is used for glass fiber production. The carbothermic reduction is carried out with graphite pellets or carbon fibers as an alternative reduction agent in crucibles within a furnace using inductive heating. The experiments are prepared and evaluated using FactSage 8.1. Carbon is used with an excess of 10% of the calculated value. The effect of temperature variation and turbulence on the carbothermic reduction process are studied. Glass fiber drawing is realized manually after remelting the secondary copper slag. The threshold for successful glass fiber production lays at a FeOx content below 10 wt%. The produced pig iron phase as well as the resulting glass fibers are characterized, while their industrial applicability is discussed.

Beneficial role of kaempferol and its derivatives from different plant sources on respiratory diseases in experimental models.

Respiratory illnesses impose a significant health burden and cause deaths worldwide. Despite many advanced strategies to improve patient outcomes, they are often less effective. There is still considerable room for improvement in the treatment of various respiratory diseases. In recent years, alternative medicinal agents derived from food plants have shown better beneficial effects against a wide variety of disease models, including cancer. In this regard, kaempferol (KMF) and its derivatives are the most commonly found dietary flavonols. They have been found to exhibit protective effects on multiple chronic diseases like diabetes, fibrosis, and so on. A few recent articles have reviewed the pharmacological actions of KMF in cancer, central nervous system diseases, and chronic inflammatory diseases. However, there is no comprehensive review that exists regarding the beneficial effects of KMF and its derivatives on both malignant- and non-malignant respiratory diseases. Many experimental studies reveal that KMF and its derivatives are helpful in managing a wide range of respiratory diseases, including acute lung injury, fibrosis, asthma, cancer, and chronic obstructive pulmonary disease, and their underlying molecular mechanisms. In addition, we also discussed the chemistry and sources, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, methods to enhance bioavailability, as well as our perspective on future research with KMF and its derivatives.

Innovative and sustainable cultivation strategy for the production of Spirulina platensis using anaerobic digestates diluted with residual geothermal water

The following study investigates the possibility of growing the Spirulina platensis (S. platensis) cyanobacteria on two agro-industrial anaerobic digestion (AD) digestates diluted with geothermal water. The two digestates (FAWD: Food and Agricultural Wastes Digestate and CDD: Cheese Diary Digestate) were selected based on their different chemical characteristics, attributed to the type of feedstock and the operating conditions used during the AD process. In the first part of the study, a screening experiment was performed in 200 mL glass tubes to evaluate the appropriate dilution factor to generate the maximum S. platensis growth using both AD digestates individually and geothermal water as sustainable alternative dilution agent. Based on the different growth parameters measured, dilution rates of 5x and 40x were chosen for CDD and FAWD respectively, as a trade-off between growth performances and quantity of water to use. Volumetric productivities of 33 ± 1 mg/L/d and 56 ± 8 mg/L/d combined with maximal concentrations of 0.52 ± 0.02 g/L and 0.69 ± 0.02 g/L were achieved when cultivating S. platensis on CDD and FAWD, respectively. In the second part, the selected experimental results were scaled-up to 6 L flat panels bioreactors and S. platensis biomass productivities of 71 and 101 mg/L/d were obtained for CDD and FAWD, respectively using sodium bicarbonate as inorganic carbon source. When regulating the pH to 8.5 with carbon dioxide (CO2) injection, cultures were able to produce up to 1.13 g/L and 0.79 g/L of S. platensis corresponding to biomass productivities of 81 and 136 mg/L/d for CDD and FAWD, respectively. In addition, S. platensis properly assimilated the ammonium present in the digestate-based culture media, with removal efficiency up to 98% in the case of the CDD substrate. The characterization of the final S. platensis biomass revealed the presence of high concentration of carbohydrates (48.6–70.3 % of dry weight) in the culture supplemented with both AD digestates. The experimental findings show the potential of reusing liquid digestate, CO2 as well as geothermal water for the sustainable production of carbohydrate-rich S. platensis biomass.

Electrospun Nanofibrous Mesh Based on PVA, Chitosan, and Usnic Acid for Applications in Wound Healing.

Injuries and diseases of the skin require accurate treatment using nontoxic and noninvasive biomaterials, which aim to mimic the natural structures of the body. There is a strong need to develop biodevices capable of accommodating nutrients and bioactive molecules and generating the process of vascularization. Electrospinning is a robust technique, as it can form fibrous structures for tissue engineering and wound dressings. The best way of forming such meshes for wound healing is to choose two polymers that complement each other regarding their properties. On the one hand, PVA is a water-soluble synthetic polymer widely used for the preparation of hydrogels in the field of biomedicine owing to its biocompatibility, water solubility, nontoxicity, and considerable mechanical properties. PVA is easy to subject to electrospinning and can offer strong mechanical stability of the mesh, but it is necessary to improve its biological properties. On the other hand, CS has good biological properties, including biodegradability, nontoxicity, biocompatibility, and antimicrobial properties. Still, it is harder to electrospin and does not possess as good mechanical properties as PVA. As these structures also allow the incorporation of bioactive agents due to their high surface-area-to-volume ratio, the interesting point was to incorporate usnic acid into the structure as it is a natural and suitable alternative agent for burn wounds treatment which avoids an improper or overuse of antibiotics and other invasive biomolecules. Thus, we report the fabrication of an electrospun nanofibrous mesh based on PVA, chitosan, and usnic acid with applications in wound healing. The obtained nanofibers mesh was physicochemically characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). In vitro biological assays were performed to evaluate the antimicrobial properties of the samples using the MIC (minimum inhibitory concentration) assay and evaluating the influence of fabricated meshes on the Staphylococcus aureus biofilm development, as well as their biocompatibility (demonstrated by fluorescence microscopy results, an XTT assay, and a glutathione (GSH) assay).

Antimicrobial Activity Studies of 3-Substituted Indole-2-one and -thione derivatives and Molecular Docking and ADME Evaluations

Increasing antibiotic resistance is an important problem for public health therefore new antimicrobial compounds are needed. In this study, the antimicrobial effects of 3-Substituted Indole-2-one and -thione derivatives were investigated. Antimicrobial effects of previously synthesized 18 different 3-substituted indole-2-one and 2-thione derivatives against 5 different microorganisms were investigated and the structure-activity relationships and drug-like properties of compounds were analyzed by molecular docking and in silico prediction studies. The in vitro antimicrobial activities of compounds were tested by microdilution method. The most active compounds were found as 2, 3, 4, 5, 6, 7, 8 at 125 μg/mL of MIC value. Compounds 2 and 3 were found to be active against S. enterica and compounds 4, 5, 6, 7, and 8 were found to be active against methicillin-resistant S. aureus. According to molecular docking studies, all compounds presented weaker binding properties than ciprofloxacin, ampicillin and gentamicin. The predicted values for molecular weight, log P, PSA, crossing the BBB, GI absorption properties and type of CYPP450 inhibition data of compounds were found promising for drug-like properties. 3-Substituted Indole-2-one and -thione derivatives can proivide an important contribution to develop alternative antimicrobial agents.

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events

BackgroundAspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. ObjectivesThis study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD. MethodsWe conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. ResultsPatient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors. ConclusionsGiven its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774)

Virtual Screening of Alternative Antiretroviral through Integrase Inhibitor from Curcuma longa L. and Tamarindus indica Compounds Against HIV-1 Infection

The development of new drugs with improved efficacy and reduced side effects is of utmost importance to combat the global HIV/AIDS pandemic. In this study, we aimed to explore the potential of natural compounds derived from Curcuma longa L. (turmeric) and Tamarindus indica (tamarind) as alternative antiretroviral agents through the virtual screening of integrase inhibitors. Curcuma longa L. and Tamarindus indica are widely recognized for their medicinal properties and have been traditionally used in various systems of medicine. These plants contain a rich repertoire of bioactive compounds that exhibit a wide range of pharmacological activities, including antiviral effects. By identifying potential integrase inhibitors from natural compounds, we aim to contribute to the discovery of novel antiretroviral agents that could be developed into effective treatments against HIV-1 infection through compoutational simulation. The computational method used in this study is sample preparation in the database and molecular docking to identify the activity of Tamarindus indica and Curcuma longa L. compounds on HIV-1. Tamarindus indica and Curcuma longa L. can be effective HIV-1 antretroviral agents because they have compounds with the most negative binding affinity consisting of Campesterol and Curcumin. Both compounds are predicted to inhibit the HIV-1 integrase enzyme to disrupt the integration of the viral genome in host cells.

Inhibitory effect of nano Stolephorus insularis and calcium hydroxide on glucosyltransferase (GTF) activity of Lactobacillus aciophilus

Background: Dental caries is the most common multifactorial infectious disease worldwide which referes to the process of destruction tooth hard tissue caused by bacterial by-products in the form of acids through carbohydrate fermentation. Lactobacillus acidophilus is one of the main cariogenic bacteria that causes caries by forming biofilms with the help ofglucosyltransferase (GTF) enzymes. Calcium hydroxide has limited antibacterial effects. Nano brown anchovy contains fluor as the active compound which has the potential as an antibacterial alternative agent. Purpose: To explain the inhibition of the combination of nano Stolephorus insularis and calcium hydroxide on the activity of the glucosyltransferase enzyme of Lactobacillus acidophilus bacteria. Methods: This study used a combination of nano Stolephorus insularis 3.125% with calcium hydroxide as a treatment and aquades as a control. The GTF enzyme was obtained from the supernatant centrifuged by Lactobacillus acidophilus in BHIB. The activity of the GTF enzyme was considered by calculating the fructose levels using High Performance Liquid Chromatography (HPLC) in a certain formula.Results: Decreased levels of fructose was obtained in the treatment group. From the results of Mann- Whitney data analysis, there were significant difference in the study groups. Conclusion: the combination of nano Stolephorus insularis with calcium hydroxide is effective to inhibit the glucosyltransferase enzyme activity of Lactobacillus acidophilus bacteria.

Synthesis, Characterization of Biogenic Copper Nanoparticles and Their Therapeutic Activity

Green synthesis of copper nanoparticles (Cu NPs) is an economical, environmentally friendly and non-toxic approach that has been the subject of research in health and industry. Therefore, in this study, Cu NPs were synthesized using Pimpinella anisum (P.anisum) seed extract and their pharmacological activities were evaluated. Characterization of Cu NPs was performed by UV-vis, FT-IR and SEM-EDX analyses. Copper metal was reduced by reacting with the seed extract and reached the maximum peak at 385 nm in the UV-vis spectra, confirming the surface plasmon resonance. FT-IR spectroscopy showed the participation of phytochemical components in P. anisum in the synthesis. SEM analysis determined that the size of the biosynthesized nanoparticles is 10-20 nm in diameter and has a spherical structure. Strong signals of copper metal were confirmed by EDX analysis. The therapeutic effect of Cu NPs was evaluated by antioxidant and antibacterial assays. The DPPH radical scavenging activity IC50 inhibition values of Cu NPs were better than the seed extract and exhibited strong antioxidant activity. Antibacterial activity was performed by the disk diffusion method and Cu NPs were more effective against gram-positive bacteria. It had the highest zone diameter (18.0±2.8 mm), especially on Bacillus subtilis bacteria. These results showed that Cu NPs may have a selective effect against drug-resistant bacteria as an alternative agent to pharmaceutical applications. This study showed that P. anisum seed extract-mediated bioconjugation of Cu NPs can be done simply, quickly and cost-effectively. As a result, Cu NPs should be supported by more detailed in vivo studies to create antioxidant and antibacterial agents.

Effect of Different Arsenic and Biochar Levels on Soil Microbial Population and Enzymatic Activity

Arsenic (As) poses a pervasive environmental contamination problem on a global scale. Human activities have significantly contributed to the extensive presence of arsenic (As) in soils. Recently, there has been growing interest in exploring the potential of biochar in addressing the issue of As-contaminated soils. This study focused on evaluating the effects of two types of biochar, namely straw biochar and iron-modified biochar, on the composition of soil microbial communities and enzymatic activity in soil contaminated with arsenic. After conducting a pot experiment for a duration of 9 months, the microbial communities and enzymatic activity were analyzed. Biochar refers to carbon-rich porous solids that are produced by heating biomasses under low oxygen conditions. These biochars are regarded as environmentally friendly sorbents that can be employed for the treatment of different types of arsenic contamination. The increased abundance of soil microbial populations and the enhanced enzymatic properties suggest that biochar fosters the richness and diversity of bacterial communities. Consequently, these improvements in the soil environment and biological quality highlight the potential of iron-modified biochar as an alternative agent for remediating arsenic-contaminated soils.

Prediction of Translational Regulation by Network Interaction in Synaptic Plasticity Induced with Centella asiatica.

Recently, human life expectancy, aging, and age-related health disorders, especially neurodegenerative diseases such as Alzheimer's disease (AD), have increased. The increasing number of AD patients causes a heavy social and economic burden on society. Since there is no treatment for AD, utilization of natural products is currently accepted as an alternative or integrative treatment agent against AD. Selection of protein databases related to synaptic plasticity was obtained from a gene bank. The protein-protein interaction (PPI) analysis was performed using Cytoscape 3.9.1. Prediction of Centella asiatica target constituents and their relationship with target synaptic plasticity was performed using STITCH, followed by GO and KEGG pathway enrichment analysis and molecular binding of ligands to presynaptic and postsynaptic receptors afterwards. From the protein database, 446 protein coding genes related to synaptic plasticity were found. PPI and KEGG pathway analysis showed potentiality to inhibit AKT and mTORC1 pathways. The targeted proteins were TSC1, Rheb, and FMRP. This study showed potentiality of Centella asiatica in AD through its binding to several proteins such as TSC1, Rheb, and FMRP. This compound in Centella asiatica was able to bind to the AKT1 and mTOR signaling pathways. Centella asiatica may behold greater potency in AD therapy.

P43 Patient tolerability of adalimumab biosimilar therapy in dermatology and rheumatology: real-world experience from a large tertiary centre

Abstract Adalimumab is widely used in the treatment of immune-mediated inflammatory diseases. It is the highest-spend drug in the National Health Service, costing more than £400 million annually. In 2018, adalimumab biosimilars became available, leading to substantial cost savings. However, patient tolerability of biosimilars remains underexplored. We evaluated the tolerability of adalimumab biosimilar therapy (Idacio®) in patients who were switched from Humira® in a large dermatology and rheumatology tertiary centre. We identified all patients issued with a prescription of Humira by dermatology [psoriasis and hidradenitis suppurativa (HS)] or rheumatology (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Behçet disease) and analysed the number who switched to Idacio between January 2021 and March 2022. Patient electronic records were reviewed up to October 2022 to identify patients who switched back to the originator product and the documented reason for the switch. The primary outcome was the numbers of patients who were switched back from the biosimilar to the originator product. Of 769 patients issued with a prescription of Humira, 694 were switched to Idacio during the study period. Of these, 134 (19.3%) switched back to the originator product, 102 of whom (76.1%) remained on this during follow-up. The highest proportion of individuals switching back to the originator product was observed in the HS population (26.7%). The most common reasons for switching back were patient-reported loss of disease control (n = 63; 47.0%), injection pain (n = 51; 38.1%) or both (n = 10; 7.5%). The median time to switch back was 197 days (interquartile range 138–280). Of 694 patients prescribed Idacio, 32 (4.6%) were switched to an alternative biologic agent during the study period. Our experience with previous biosimilar switches within rheumatology and dermatology (etanercept, rituximab and infliximab) has resulted in few patients requiring a switch back to the originator. Our data indicate that around one in five patients in our study population switched back to the originator product. The higher proportion of patients citing injection pain may relate to the citrate excipient content or larger injection volume of the biosimilar Idacio. Loss of efficacy with time is well established with adalimumab, in part due to antidrug antibodies, and cannot be specifically attributed to the biosimilar. Switching may alter a patient’s confidence in the drug, which is particularly important when it may be a first-line therapy or the only approved biologic for a condition. Data on switch-back rates for other adalimumab biosimilars is required to understand how generalizable our findings are and the potential economic implications.