Histidine Research Articles

Regulation of histidine metabolism by Lactobacillus Reuteri mediates the pathogenesis and treatment of ischemic stroke

Increasing evidence has underscored the significance of post-stroke alterations along gut–brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut–brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Tin-Lead Perovskite Solar Cells with Preferred Crystal Orientation by Buried Interface Approach.

Mixed tin-lead perovskite solar cells (PSCs) have garnered much attention for their ideal bandgap and high environmental research value. However, poly (3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS), widely used as a hole transport layer (HTL) for Sn-Pb PSCs, results in unsatisfactory power conversion efficiency (PCE) and long-term stability of PSCs due to its acidity and moisture absorption. A synergistic strategy by incorporating histidine (HIS) into the PEDOT: PSS HTL is applied to simultaneously regulate the nucleation and crystallization of perovskite (PVK). HIS neutralizes the acidity of PEDOT: PSS and enhances conductivity. Especially, the coordination of the C═N and -COO- functional groups in the HIS molecule with Sn2+ and Pb2+ induces vertical growth of PVK film, resulting in the release of residual surface stress. Additionally, this strategy also optimizes the energy level alignment between the perovskite layer and the HTL, which improves charge extraction and transport. With these cooperative effects, the PCE of Sn-Pb PSCs reaches 21.46% (1 sun, AM1.5), maintaining excellent stability under a nitrogen atmosphere. Hence, the buried interface approach exhibits the potential for achieving high-performance and stable Sn-Pb PSCs.

Modified SnO2 Electron Transport Layer by One‐Step Doping with Histidine in Perovskite Solar Cells

Tin dioxide (SnO2), one of the best electron transport layer materials for perovskite solar cells (PSCs), has high electrical conductivity and low photocatalytic activity. However, the defects in its inside and surface result in nonradiative recombination at the SnO2/perovskite interface. Complex and time‐consuming passivation methods are not conducive to the commercialization of PSCs, and simple passivation strategies should be used to improve the photovoltaic performance of the devices. Herein, a facile and efficient method is proposed to simultaneously passivate the inside and surface defects by adding histidine (HIS) to SnO2 colloidal solution. This one‐step doping strategy also modulates carrier dynamics at the SnO2/perovskite interface. HIS reduces suspended hydroxyl groups, oxygen vacancies, and uncoordinated Sn4+ defects on the surface of SnO2, as well as uncoordinated Pb2+ and halogen vacancy defects at the buried interface of perovskite. Surprisingly, HIS can prevent perovskite from decomposition to form PbI2, which further decomposes to photoactive metallic Pb0 and I, causing ion migration in PSC. As a result, the PSC efficiency has significantly improved 23.11% after HIS doping. The efficiency of unencapsulated device with HIS is 94% of the primary efficiency after storage in relative humidity = 70 ± 5% for 1000 h.

Deciphering competitive interactions: Phosphate and organic matter binding on goethite through experimental and theoretical insights

The adsorption of phosphorus (P) onto active soil surfaces plays a pivotal role in immobilizing P, thereby influencing soil fertility and the filter function of soil to protect freshwater systems from eutrophication. Competitive anions, such as organic matter (OM), significantly affect the strength of this P-binding, eventually controlling P mobility and release, but surprisingly, these processes are insufficiently understood at the molecular level. In this study, we provide a molecular-level perspective on the influence of OM on P binding at the goethite-water interface using a combined experimental-theoretical approach. By examining the impact of citric acid (CIT) and histidine (HIS) on the adsorption of orthophosphate (OP), glycerol phosphate (GP), and inositol hexaphosphate (IHP) through adsorption experiments and molecular dynamics simulations, we address fundamental questions regarding P binding trends, OM interaction with the goethite surface, and the effect of OM on P adsorption. Our findings reveal the complex nature of P adsorption on goethite surfaces, where the specific OM, treatment conditions (covering the surface with OM or simultaneous co-adsorption), and initial concentrations collectively shape these interactions. P adsorption on goethite exhibits a binding strength increasing in the order of GP < OP < IHP. Crucially, this trend remains consistent across all adsorption experiments, regardless of the presence or absence of OM, CIT, or HIS, and irrespective of the specific treatment method. Notably, OP is particularly susceptible to inhibition by OM, while adsorption of GP depends on specific OM treatments. Despite being less sensitive to OM, IHP shows reduced adsorption, especially at higher initial P concentrations. Of significance is the strong inhibitory effect of CIT, particularly evident when the surface is pre-covered, resulting in a substantial 70 % reduction in OP adsorption compared to bare goethite. The sequence of goethite binding affinity to P and OM underscores a higher affinity of CIT and HIS compared to OP and GP, suggesting that OM can effectively compete with both OP and GP and replace them at the surface. In contrast, the impact of OM on IHP adsorption appears insignificant, as IHP exhibits a higher affinity than both CIT and HIS towards the goethite surface. The coverage of goethite surfaces with OM results in the blocking of active sites and the generation of an unfavorable electric potential and field, inhibiting anion adsorption and consequently reducing P binding. It is noteworthy that electrostatic interactions predominantly contribute more to the binding of P and OM to the surface compared to dispersion interactions.

Natural moisturising factor constituents in South African nursing students.

The majority of South African healthcare workers are Black Africans with dark-pigmented skin. Studies on how the markers of skin barrier function and natural moisturising factor (NMF) compare between dark and light-pigmented skin are limited. Quantifying NMF in a nursing student population during their practical training at university may provide valuable insight into their potential susceptibility to skin conditions associated with low NMF. The objectives of this study were to quantify and compare NMF content of Black African, Mixed Race and White nursing students from their dominant dorsal hand. Forty-nine White, 32 Black African and 5 Mixed Race nursing students participated in this study. Tape strip samples were collected from the participants' dominant dorsal hand and NMF content was measured, including histidine (HIS), pyrrolidone carboxylic acid (PCA), trans-urocanic acid (t-UCA) and cis-urocanic acid (c-UCA), as well as cytokines interleukin-1 alpha (IL-1α) and interleukin-1 receptor antagonist (IL-1RA). No statistically significant differences in PCA, t-UCA, c-UCA, IL-1α or IL-1RA were found between Black African and White nursing students. HIS was significantly (p = 0.001) higher in White nursing students when compared to Black African students. The ratio of tot-UCA/HIS was significantly higher in Black Africans (p = 0.0002) when compared to White nursing students. No significant differences were established in NMF content between White and Black African nursing students, other than HIS which was significantly higher in White students than in Black African students. Different HIS levels between the racial groups suggest variation in histidase activity which may be related to skin pH and pigmentation. This finding may suggest that nursing students at the beginning of their careers may have similar susceptibility to skin diseases related to NMF.

A Disposable Sensor for Rapid Histamine Detection in Fish Using Molecularly Imprinted Carbon Paste Electrode

Introduction: Histamine (HM), a toxic compound, is produced due to an enzymatic reaction when histidine (HS)-rich red fish such as tunas and other fish and their processed products are improperly stored, e.g., leaving them at room temperature. With the increasing popularity of raw fish consumption, HM analysis is mandatory for these fish in various countries. However, the conventional immunoassay method is time-consuming, costly, and technically demanding, burdening wholesalers heavily.Molecularly Imprinted Polymers-based materials are attractive materials for sensor fabrication due to their high selectivity, stability, and ease of production. In this study, we attempted to develop a Molecularly Imprinted Polymer grafted Carbon Paste (MIP-CP) for histamine sensing. Experimental Methods First, a radical polymerization initiator was fixed on the surface of graphite particles [1]. Next, histamine dihydrochloride, itaconic acid, and ethylene glycol dimethacrylate (EDMA) were dissolved in a mixture of distilled water and dimethylformamide to prepare a polymerization solution. The polymerization solution and initiator-fixed graphite were placed in a quartz tube and irradiated with a xenon lamp for 1 hr. HM was extracted and removed using acetic acid. MIP-CP was prepared by mixing MIP-grafted graphite and silicon oil containing ferrocene in a 7:3 weight ratio. Non-imprinted polymer (NIP)-CP was also prepared using the same procedure, except that HM was not added.Differential pulse voltammetry (DPV) was performed with electrodes packed with the obtained MIP-CPs on a disposable chip [2]. The performance of the HM sensor was evaluated based on the relationship between the oxidation current of ferrocene and HM concentration. (Measurement range 0 μg/mL~100 μg/mL) Experimental results The dependence of the oxidation current density on HM concentration at the NIP and MIP electrodes was confirmed (0.0085 μA-mL/μg, R²=0.9357). The increase in current density with increasing HM concentration at the MIP-CP electrode was more than three times greater than at the NIP-CP electrode. This confirmed that MIP-CP exhibited current changes corresponding to the interaction between HM and HM-imprinted sites. Furthermore, the current increased linearly with increasing HM concentration from 0-100 µg/mL. This dynamic range includes 50 µg/mL, which is considered the lower limit of acceptable Hm concentration in fish meat.However, the current value was constant for HS concentration at 0.75 µA over the range of 40-100 µg/mL and below. Therefore, the sensor is saturated with HS at concentrations above 40 µg/mL, and histidine interference can be excluded by subtracting 0.75 µA from the current value obtained when measuring the fish meat sample. Conclusion We successfully developed a reagentless, disposable histamine sensor using MIP-CP, which provides a rapid, reliable, and cost-effective method for histamine detection in fish.

HEMA-based macro and microporous materials for CO2 capture

New polymeric macroporous materials based on poly 2-hydroxyethyl methacrylate (pHEMA) were synthesized and tested to adsorb CO2. To this purpose, bio and affordable amine-based molecules such as lysine (LYS) and histidine (HIS) were selected as CO2 active sites and used to functionalize HEMA monomer before its crosslinking polymerization. The as-prepared monomers and polymers were characterized by using Nuclear Magnetic Resonance (NMR), Fourier Infrared Spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), and Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray (EDX). Compared to materials reported in the recent literature, all produced ones provide exceptional adsorption capacity in the 162–193 ppm range. In particular, H-HEMA-LYS exhibits the best adsorption grade, well-fitting the Linear Driving Force (LFD) model. H-HEMA-LYS reusability was also tested for up to 5 cycles without significant loss in capture performance. Finally, to get insight into the role of morphology in CO2 adsorption, two diverse macroporous structures were synthesized (hydrogels and cryogels) for both HIS and LYS-based materials. As it turns out, hydrogel formulations of an average area ranging from 15.5 to 230 μm2 adsorb 12% more than cryogels with higher values (266–605 μm2).

Effect of Cyclodextrin Complex Formation on Solubility Changes of Each Drug Due to Intermolecular Interactions between Acidic NSAIDs and Basic H2 Blockers.

One of the solubilization of poorly water-soluble drugs is the use of cyclodextrin (CD)-based inclusion complexes. On the other hand, few studies have investigated how CD functions on the solubility of drugs in the presence of multiple drugs that interact with each other. In this study, we used indomethacin (IND) and diclofenac (DIC) as acidic drugs, famotidine (FAM) and cimetidine (CIM) as basic drugs, and imidazole (IMZ), histidine (HIS), and arginine (ARG) as compounds structurally similar to basic drugs. We attempted to clarify the effect of β-CD on the solubility change of each drug in the presence of multiple drugs. IND and DIC formed a eutectic mixture in the presence of CIM, IMZ, and ARG, which greatly increased the intrinsic solubility of the drugs as well as their affinity for β-CD. Furthermore, the addition of high concentrations of β-CD to the DIC-FAM combination, which causes a decrease in solubility due to the interaction, improved the solubility of FAM, which was decreased in the presence of DIC. These results indicate that β-CD synergistically improves the solubility of drugs in drug-drug combinations, where the solubility is improved, whereas it effectively improves the dissolution rate of drugs in situations where the solubility is reduced by drug-drug interactions, such as FAM-DIC. This indicates that β-CD can be used to improve the physicochemical properties of drugs, even when they are administered in combination with drugs that interact with each other.

Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study.

An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.

Zinc/iron-regulated transporter-like protein gene family in Theobroma cacao L: Characteristics, evolution, function and 3D structure analysis.

The zinc/iron-regulated transporter-like protein (ZIP) gene family first identified in plants is highly distributed in the plant kingdom. This family has previously been reported to transport several essential and non-essential cationic elements, including those toxic to many economically important crops such as cacao (Theobroma cacao L.). In this article, we present a detailed study on physicochemical properties, evolution, duplication, gene structure, promoter region and TcZIP family three-dimensional protein structure. A total of 11 TcZIP genes have been identified to encode proteins from 309 to 435 aa, with localization in the plasma membrane and chloroplast, containing 6-9 putative domains (TM). Interspecies phylogenetic analysis subdivided the ZIP proteins into four groups. Segmental duplication events significantly contributed to the expansion of TcZIP genes. These genes underwent high pressure of purifying selection. The three-dimensional structure of the proteins showed that α helix conformations are predominant with several pocket sites, containing the metal binding site, with the residues leucine (LEU), alanine (ALA), glycine (GLY), serine (SER), lysine (LYS) and histidine (HIS) the most predicted. Regarding the analysis of the protein-protein interaction and enrichment of the gene ontology, four biological processes were assigned, the most important being the cation transport. These new discoveries expand the knowledge about the function, evolution, protein structures and interaction of ZIP family proteins in cacao and contribute to develop cacao genotypes enriched with important mineral nutrients as well as genotypes that bioaccumulate or exclude toxic metals.

Evaluation of synthesized biosurfactants as promising corrosion inhibitors and alternative antibacterial and antidermatophytes agents

This study investigated different amino acid-based surfactants (AASs), also known as biosurfactants, including sodium N-dodecyl asparagine (AS), sodium N-dodecyl tryptophan (TS), and sodium N-dodecyl histidine (HS) for their potential anticorrosion, antibacterial, and antidermatophyte properties. The chemical and electrochemical techniques were employed to examine the copper corrosion inhibition efficacy in H2SO4 (1.0 M) solution at 298 K. The results indicated their promising corrosion inhibition efficiencies (% IEs), which varied with the biosurfactant structures and concentrations, and the concentrations of corrosive medium. Higher % IEs values were attributed to the surfactant adsorption on the copper surface and the production of a protective film. The adsorption was in agreement with Langmuir adsorption isotherm. The kinetics and mechanisms of copper corrosion and its inhibition by the examined AASs were illuminated. The surfactants behaved as mixed-kind inhibitors with minor anodic priority. The values of % IEs gained from weight loss technique at a 500 ppm of the tested surfactants were set to be 81, 83 and 88 for AS, HS and TS, respectively. The values of % IEs acquired from all the applied techniques were almost consistent which were increased in the order: TS > HS ≥ AS, establishing the validity of this study. These surfactants also exhibited strong broad-spectrum activities against pathogenic Gram-negative and Gram-positive bacteria and dermatophytes. HS exhibited the highest antimicrobial activity followed by TS, and AS. The sensitivity of pathogenic bacteria varied against tested AASs. Shigella dysenteriae and Trichophyton mantigrophytes were found to be the most sensitive pathogens. HS exhibited the highest antibacterial activity against Shigella dysenteriae, Bacillus cereus, E. coli, K. pneumoniae, and S. aureus through the formation of clear zones of 70, 50, 40, 39, and 35 mm diameters, respectively.AASs also exhibited strong antifungal activity against all the tested dermatophyte molds and fungi. HS caused the inhibition zones of 62, 57, 56, 48, and 36 mm diameters against Trichophyton mantigrophytes, Trichophyton rubrum, Candida albicans, Trichosporon cataneum, and Cryptococcus neoformans, respectively. AASs minimal lethal concentrations ranged between 16 to 128 µg/ml. HS presented the lowest value (16 µg/ml) against tested pathogens followed by TS (64 µg/ml), and AS (128 µg/ml). Therefore, AASs, especially HS, could serve as an effective alternative antimicrobial agent against food-borne pathogenic bacteria and skin infections-associated dermatophyte fungi.

Diverse Effects of Amino Acids on Monascus Pigments Biosynthesis in Monascus purpureus.

Amino acids could act as nitrogen sources, amido group donors, or bioactive molecules in fungi fermentation, and consequently, play important roles in Monascus pigments (MPs) biosynthesis. But the understanding of the effects of various amino acids on MPs biosynthesis is still incomprehensive. In this work, 20 free amino acids were added to the fermentation medium to evaluate their effects on MPs biosynthesis in Monascus purpureus RP2. Six amino acids, namely, histidine (HIS), lysine (LYS), tyrosine (TYR), phenylalanine (PHE), methionine (MET), and cysteine (CYS), were selected as the valuable ones as they exerted significant effects on the production yield and even on the biosynthesis metabolic curves of MPs. Moreover, the dose-dependent and synergistic effects of valuable amino acids on MPs biosynthesis were observed by tests of serial concentrations and different combinations. In addition, it revealed that HIS and MET were the prominent amino acids with dominant and universal influences on MPs biosynthesis. The analog compounds of HIS (amitrole) and MET [calcium 2-hydroxy-4-(methylthio)] were added to the fermentation medium, and the results further confirmed the extraordinary effects of HIS and MET and their analogs on MPs biosynthesis. Furthermore, the gene transcription profile indicated that a differential expression pattern was observed in the polyketide synthase (PKS) cluster responsible for MPs biosynthesis in response to HIS and MET, revealing that they could oppositely regulate MPs biosynthesis in different ways. These findings would benefit the understanding of MPs biosynthesis regulation mechanism in M. purpureus and contribute to the industrial production of MPs by fermentation.

Development of an equipment free paper based fluorimetric method for the selective determination of histidine in human urine samples

A direct fluorimetric method, employing μicro-analytical paper-based devices (μ-PADs) for the selective determination of histidine (HIS) is described. The suggested method exploits the fluorescence emission of histidine after its rapid reaction with o-phthalaldehyde (OPA) at a basic medium (pH = 10) on the surface of a paper device with the application of a UV lamp at 354 nm. The devices are inexpensive and are composed of chromatographic paper and wax barriers. The analytical protocol is easily applicable with minimal technical expertise and without the need of expensive experimental apparatus. The user has to add a test sample, illuminate the device with a UV lamp, and read the fluorescence of the sensing area using a simple imaging device such as a cell-phone camera. The method is free from common interferences likely to affect the measurement of histidine and is selective among all other amino acids. This analytical procedure was optimized and validated, paying special attention to its intended application. The detection limits are as low as 1.8 μM with very satisfactory precision ranging from 6.4% (intra-day) to 8.9% (inter-day). Random urine samples from adult volunteers (n = 5) were successfully analyzed and HIS content ranged between 260 and 1114 μmol L−1 with percentage recoveries in the range of 78.2 and 124.6%.

In-depth insight into the inhibition mechanism of the modified and combined amino acids corrosion inhibitors: “intramolecular synergism” vs. “intermolecular synergism”

In this work, amino acid (L-histidine (LHD)) and 1-phenylthiourea (PT) were mixed as the combined corrosion inhibitors (LHD + PT). Meanwhile, LHD was also modified with phenyl isothiocyanate to develop a novel corrosion inhibitor (phenylcarbamothioyl)histidine (PT-HD), which has a combined structure of LHD and PT. Then LHD + PT is the “intermolecular synergism”, while PT-HD could be regarded as the “intramolecular synergism” of LHD and PT. The inhibition performances of LHD + PT and PT-HD for the corrosion of carbon steel in CO2-saturated formation water were investigated by electrochemical tests and surface analyses. Additionally, the intrinsic difference in the inhibition performance and mechanism of LHD + PT and PT-HD were in-depth revealed by theoretical calculations. The experimental results indicate that PT-HD exhibits better inhibition performance than LHD + PT (inhibition efficiency of 99.2% for 0.4 mM LHD + PT and 99.3% for 0.4 mM PT-HD), i.e., the “intramolecular synergistic inhibition effect” is stronger than the “intermolecular synergistic inhibition effect”. The theoretical calculations also indicate that PT-HD has stronger adsorption ability and more effective prevention to the invasion of aggressive species. The higher inhibition efficiency of PT-HD is associated with the fact that the LHD and PT fragments in PT-HD molecule are closely linked by chemical bond, forming a more compact adsorbed inhibitor film on steel surface.

Silage Feeding with Water Hyacinth in the Tropics: A Research Note

Water hyacinth has ecological significance in addition to its agricultural and energy uses. Lower quality silage is defined in this paper as requiring nitrogen supplementation and treatment to improve nutritive value (NV). Ensilage of water hyacinth as a test case centers largely around the process to optimize protein nitrogen retention in silage-based regimens. A previous hypothesis proposed earlier by the author of that of functional amino acid ratios [tyrosine (TYR): large neutral amino acids (LNAA), tyrosine (TYR): phenylalanine (PHE)] were subsequently found to be counter to what the given schemata predicts. And subsequently with another study there was no corroborative evidence for it to support the espoused hypothesis using the same schemata. The role of N status is still the most viable option among factors from studies continuing how amino acids like histidine (HIS) and arginine (ARG) and their growth-related endocrine functions play a role. There are other schemas illustrating non-homeostatic type regulation with protein intake. To focus on molecular-level mechanisms to ruminal protein digestion it is becoming clear what factors in feed and microbial cell fermentation contribute to optimizing microbial cell protein (MCP) synthesis from ATP with organic matter (OM) digestibility and preformed amino acids (PFAA) from peptides and free amino acids in addition to non-protein nitrogen (NPN), the former more efficiently assimilated in MCP than NPN in the rumen. Accordingly, it has been recommended that soluble proteins fed to dairy cows not exceed microbial requirements along with high dietary escape protein fed with a sufficient amino acid profile to meet dairy production.

Synthesized Drug from Medicinal Plant phytochemicals Effectively Targets ECM1 Gene Mutations in Ulcerative Colitis

: Ulcerative colitis (UC); an inflammatory bowel disease primarily affects the mucosa of the colon. Depending on its mode of appearance, it can affect either the entire colon or even the distal rectum. UC can manifest in both genders and every generation, but most generally appear in people between the ages of 15 and 30. The extracellular matrix protein-1 (ECM1) gene is an important candidate, mutations leading to tissue damage in patients with ECM1 single-nucleotide polymorphisms are likely to intensify tissue damage caused by Metalloproteinase9 resulting in UC. In this analysis, approval for the synthesis of Chemical Compound was obtained from the scientific committee of the Department of Traditional Chinese Medicine, Qilu Hospital, China. Several derivatives used as UC therapy were selected to build the pharmacophore model, using a ligand-based pharmacophore modeling approach and virtual screenings were done for the identification of suitable drug compounds. The selected compound was then synthesized in-vitro and validated using the molecular docking technique. The synthesized compound fulfills all the characteristics of the non-toxic existence of other drug-likeness laws. The specific interactive amino acids found in the docked complex are arginine (ARG):47, lysine (LYS):54, phenylalanine (PHE):141, aspargine (ASN):51, serine (SER):219, histadine (HIS):144, PHE:214, valine(VAL):220, tyrosine(TYR):145, and TYR:284. The interaction of the synthesized compound with mutated TYR:284 of ECM1 confirmed the viability and safety of a drug molecule as a medication in Ulcerative Colitis care. In the future, its validity can be explored in the laboratory and this synthesized compound can be used as a medication target in clinical studies against TYR:284 mutation in the ECM1 gene.

Complexation reduces nickel toxicity to purple sea urchin embryos (Strongylocentrotus purpuratus), a test of biotic ligand principles in seawater

The potential for Ni toxicity in seawater is of concern because of mining and processing activities in coastal regions. Determining Ni speciation is vital to understanding and predicting Ni toxicity and for bioavailability-based nickel risk assessment. The goal of this study was to characterize the complexation of Ni in relation to toxicity using embryological development of purple sea urchin (S. purpuratus). It was predicted that free ion [Ni2+] would be a better predictor of toxicity than total dissolved Ni concentrations (NiD). Synthetic ligands with known logKf values (Ethylenediaminetetraacetic acid (EDTA), Nitrilotriacetic acid (NTA), tryptophan (TRP), glutamic acid (GA), histidine (HD), and citric acid (CA)) were used to test the assumptions of the biotic ligand model (BLM) for Ni in seawater. [NiD] was measured by graphite furnace atomic absorption spectroscopy (GFAAS) and Ni2+ was first quantified using the ion-exchange technique (IET) and then concentrations were measured by GFAAS; [Ni2+] was also estimated using aquatic geochemistry modelling software (Visual Minteq). The mean EC50 values for [NiD] in unmodified artificial seawater control was 3.6 µM (95% CI 3.0–4.5) [211 µg/L 95% CI 176–264] and the addition of ligands provided protection, up to 6.5-fold higher [NiD] EC50 for EDTA. Compared to the control, measured EC50 values based on total dissolved nickel were higher in the presence of ligands. As predicted by BLM theory, [Ni2+] was a better predictor of Ni toxicity with 17% variability in EDTA and CA media while there was 72% variability in the prediction of Ni toxicity with total dissolved Ni. The results of this research provide support for the application of BLM- based prediction models for estimating Ni impacts in seawater.

Analysis and mapping quantitative trait loci for histidine content in barley (Hordeum vulgare L.) using microsatellite markers

Mining the gene of histidine content in barley grain helps with the breeding of functional barley varieties. The study constructed a recombinant inbred lines (RILs) containing 193 families derived from the cross between Ziguangmangluoerling (ZGMLEL) (♀) and Schooner No.3 (♂). The histidine (HIS) content in the grain of the mapping population and its parents were determined by an automatic amino acid analyzer. The HIS content of ZGMLEL was 0.53 mg/g. The grain HIS content of Schooner No. 3 was 0.21 mg/g, and the grain HIS content of population ranged from 0.23 to 0.54. Genetic linkage maps, including those of seven chromosomes of barley, were constructed by using 180 pairs of simple sequence repeat (SSR) markers, with a total genetic distance of 2671.03 cM and average marker spacing of 14.84 cM. Quantitative trait locus (QTL) IciMappingV3.3 was used to analyze QTL of HIS content in barley grains, and three QTLs were detected. Mapping results showed that the three loci were located on chromosomes 2H, 4H, and 7H, respectively. The major QTL with a contribution rate of 10.11% was located on barley chromosome 4H (HVBAMMGB84-BMAG0808). The additive effect is positive (0.025). Thus, it comes from the high-value parent ZGMLEL. Another major QTL with a contribution rate of 13.75% was located on barley chromosome 7H (GBM1303-GMS056). The minor QTL with a contribution rate of 6.01% was located on chromosome 2H (Scssr03381-Scssr07759). The additive effects of 4H and 7H QTLs were negative (− 0.02 and − 0.033). So, they came from the male parent Schooner. The results provided a reference for further fine mapping, cloning, and transformation of HIS genes in barley grains.

Research progress on two-component signal transduction systems in Porphyromonas gingivalis.

Porphyromonas gingivalis (P. gingivalis), a Gram-negative oral anaerobe, is considered to be a major pathogenic agent involved in the onset and progression of chronic periodontitis. P. gingivalis must be able to perceive and respond to the complicated changes in host to survive the environmental challenges, in which the two-component signal transduction systems (TCSs) play critical roles by connecting input signals to cellular physiological output. Canonical TCS consists of a sensor histidine kinase and a cognate response regulator that functions via a phosphorylation cascade. In this review, the roles of TCSs in P. gingivalis were demonstrated by illustrating the target genes and modulation modes, which may help elucidate the underlying mechanisms in future studies.

Custodiol versus extracellular crystalloid cardioplegia in mitral valve replacement in patients with low ejection fraction

Background The use of cardioplegia solution is aimed to avoid myocardial muscle damage, leading to poor contraction and abnormal increased release of cardiac biomarkers enzymes during cardiac arrest. It remains the primary method for myocardial protection against ischemia–reperfusion injury during cardiac surgery. Cardioplegia was first presented as an agent for hypothermic hyperkalemic arrest. Blood was then introduced as a vehicle to convey potassium to the heart. Histidine–tryptophan–ketoglutarate solution is safe and used as a single dose that can last for up to 3 h. Comparison between custodiol cardioplegia and cold blood cardioplegia still remains a big debate till now. Objective To compare the clinical outcomes of custodiol solution with cold blood cardioplegia in mitral valve replacement (MVR) with cardiac ejection fraction less than 45%. Patients and methods This single‑center randomized prospective study was carried out from January 2018 till June 2019 at Ain Shams University hospitals. Overall, 65 patients with poor left ventricular function undergoing mitral valve replacement were divided randomly according to type of myocardial protection into two groups: group A included 30 patients who received custodiol cardioplegia, and group B included 35 patients who received cold blood cardioplegia. Data from each group were collected and compared with each other. Results Baseline demographic and intraoperative data showed no significant difference between the two groups. The need for inotropic support, length of mechanical ventilation, and ICU stay were statistically nonsignificant between the two groups. There was a statistically significant difference regarding the rhythm upon declamping [ventricular fibrillation (VF) in 17 (56.7%) cases in group A and nine (25.7%) cases in group B (P=0.016)], and also there was a significant difference in times of defibrillation cardioversion (DC) shock given after declamping (P=0.005). Overall mortality shows a statistically nonsignificant difference. There is a significant difference in postoperative echo assessment for both groups [ejection fraction in group A: 53.17±7.73 compared with 49.06±7.170 in group B (P=0.031)], and there is also a difference in hemoglobin postoperatively, with 10.35±0.843 in group A compared with 10.88±0.798 in group B (P=0.013). Conclusion Cardiac arrest using custodiol cardioplegia is a good choice in mitral valve replacement with the advantage of giving only one dose of cardioplegia without interruption of the operation, and also it gives good postoperative echo results than cold blood cardioplegia. Its disadvantages are lower hemoglobin levels postoperatively and hyponatremia during bypass in comparison with cold blood cardioplegia.