Azelaic Research Articles

An overview on Azelaic Acid: Biosynthesis, signalling and the action under stress conditions in plants

Plants are exposed to various biotic and abiotic stress factors throughout their lives. For this reason, they have developed some defense mechanisms. They can induce systemic acquired resistance (SAR), which provides long-lasting protection against diverse pathogen attacks. In recent years, several chemical inducers (salicylic acid, glyceraldehyde-3-phosphate, azelaic acid, pipecolic acid, and dehydroabietic acid) have been determined to play roles in this mechanism. The transfer of these signal molecules from infected tissue to non-infected tissues through phloem provides potent defence communication. Azelaic acid is a well-known molecule that triggers salicylic acid accumulation under biotic stress as a priming factor to induce SAR, although little is known about its role under abiotic stress. Here, this review aims to call attention to the effects of AzA under abiotic stress conditions as well as biosynthesis, transport and signalling.

Identification and characterization of endogenous biomarkers for hepatic vectorial transport (OATP1B3-P-gp) function using metabolomics with serum pharmacology

The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the drug. Unfortunately, there is still a lack of effective means to evaluate the disposal ability mediated by transporters. The present study was designed to identify a suitable endogenous biomarker for the assessment of OATP1B3-P-gp function in the liver. We established stably transfected HEK293T-OATP1B3 and HEK293T-P-gp cell lines. Results showed that azelaic acid (AzA) was an endogenous substrate for OATP1B3 and P-gp using serum pharmacology combined with metabolomics. There is a good correlation between the serum concentration of AzA and probe drugs of rOATP1B3 and rP-gp when rats were treated with their inhibitors. Importantly, after 5-fluorouracil-induced rat liver injury, the relative mRNA level and expression of rOATP1B3 and rP-gp were markedly down-regulated in the liver, and the serum concentration of AzA was significantly increased. These observations suggest that AzA is an endogenous substrate of both OATP1B3 and P-gp, and may serve as a potential endogenous biomarker for the assessment of the function of OATP1B3-P-gp for the prediction of changes in the pharmacokinetics of drugs transported by OATP1B3-P-gp in liver disease states.

Evaluating the effects of azelaic acid in the metabolism of Arabidopsis thaliana seedlings through untargeted metabolomics and ionomics approaches.

The present study demonstrates that low concentrations of azelaic acid (AZA) significantly impact the metabolism of Arabidopsis thaliana seedlings, leading to imbalances in numerous minerals and metabolites due to AZA-induced stress. Untargeted metabolomic analyses were conducted on untreated and AZA-treated seedlings at two time points: 7 and 14 days after treatment initiation. The results revealed a general accumulation of sugars (e.g., glucose, mannose, xylose), amino acids (e.g., lysine, GABA, threonine, glutamine), and organic acids (e.g., glutaric acid, shikimic acid, succinic acid) in AZA treated-seedlings, suggesting that AZA triggers stress responses in Arabidopsis. Ionomic analysis revealed that AZA induces phosphorus deficiency, which plants compensate by increasing malate content in the roots. Additionally, AZA treatment induced putrescine accumulation within the root, a metabolic biomarker of potassium deficiency and plant stress. The metabolomic profile showed elevated levels of different specialized metabolites, such as nitrogen- and sulphur-containing compounds, and altered levels of various phytohormones, including jasmonates and brassinosteroids, implicated in plant protection under biotic and/or abiotic stresses. These findings support the hypothesis that AZA's mode of action is associated with an auxin imbalance, suggesting its function as an auxinic herbicide. The observed increases in starch and jasmonates, coupled with the disruptions in potassium homeostasis, are linked to the previously reported alterations in the auxin transport, root architecture and gravitropic root response. Statistical analyses were applied, including Kruskal-Wallis tests for ionomic data, as well as multifactor analysis, Principal Component Analysis, Orthogonal Partial Least Squares-Discriminant Analysis, and enrichment pathway analysis for metabolomic data, ensuring the robustness and validity of these findings.

Guidelines of care for the management of acne vulgaris

Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9years or older. The objective of this study was to provide evidence-based recommendations for the management of acne. A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. Analysis is based on the best available evidence at the time of the systematic review. These guidelines provide evidence-based recommendations for the management of acne vulgaris.

The exometabolome of microbial communities inhabiting bare ice surfaces on the southern Greenland Ice Sheet.

Microbial blooms colonize the Greenland Ice Sheet bare ice surface during the ablation season and significantly reduce its albedo. On the ice surface, microbes are exposed to high levels of irradiance, freeze-thaw cycles, and low nutrient concentrations. It is well known that microorganisms secrete metabolites to maintain homeostasis, communicate with other microorganisms, and defend themselves. Yet, the exometabolome of supraglacial microbial blooms, dominated by the pigmented glacier ice algae Ancylonema alaskanum and Ancylonema nordenskiöldii, remains thus far unstudied. Here, we use a high-resolution mass spectrometry-based untargeted metabolomics workflow to identify metabolites in the exometabolome of microbial blooms on the surface of the southern tip of the Greenland Ice Sheet. Samples were collected every 6 h across two diurnal cycles at 5 replicate sampling sites with high similarity in community composition, in terms of orders and phyla present. Time of sampling explained 46% (permutational multivariate analysis of variance [PERMANOVA], pseudo-F = 3.7771, p = 0.001) and 27% (PERMANOVA, pseudo-F = 1.8705, p = 0.001) of variance in the exometabolome across the two diurnal cycles. Annotated metabolites included riboflavin, lumichrome, tryptophan, and azelaic acid, all of which have demonstrated roles in microbe-microbe interactions in other ecosystems and should be tested for potential roles in the development of microbial blooms on bare ice surfaces.

Discrimination of the geographical origin of gluten-free teff grains from northwestern parts of Ethiopia by fatty acid analysis

Teff (Eragrostis tef) is a gluten-free cereal, and the consumer also prefers teff due to its nutritional composition. Determining the geographical origin of teff is important to select the right product for consumers. The quality and consumer preference of teff varies based on their production origin; consequently, their prices differ significantly. This work studied the profile of fatty acids in seventy-two teff samples by using gas chromatography coupled with mass spectrometry (GC-MS) and identifying the markers to discriminate the geographical origin of teff depending on their production region. Principal component analysis (PCA) and linear discriminat Analysis (LDA) were used to visualize data trends, and construct classification models for teff samples according to their geographical origins. Thirty different fatty acids were detected in all of the collected teff samples. The total mean concentration of fatty acids ranged from 739.85 to 938.06 mg/100g across the six districts in the three zones (East Gojjam,Awi, and West Gojjam). Stearic acid,trans-vaccenic acid, linoleic acid, azelaic acid, and capric acid were the most discriminating fatty acids of teff grains between East Gojjam and West Gojjam zones, while palmitic, palmitoleic, and oleic acid discriminated Awi zone teff samples from the other zones. The recognition and prediction abilities of the LDA model for the classification of the production zones were 98.6 % and 94.4 %, respectively. Hence, the fatty acid profiles combined with multivariate data analysis too can be used in the determination of the geographical origin of teff grains.

Study of Red Algae (Eucheuma denticulatum (Burman) Collins et Harvey) Extract Bioactive Compounds using Liquid Chromatography Mass Spectroscopy - Mass Spectroscopy

Research has been carried out on the Study of Red Algae (Eucheuma denticulatum (Burman) Collins et Harvey) Extract Bioactive Compounds Using Liquid Chromatography Mass-Mass Spectroscopy (LCMS-MS). This study aims to determine the bioactive compounds produced in this red algae extract by means kinetic maceration of extraction. Reading of bioactive compounds using LCMS-MS to obtain compound results, compound structures, and molecular weights. The results show that there are 22 bioactive compounds contained in this plant. Consist of : 4-Dodecylbenzenesulfonic acid, NP-009092, 6-Hydroxycaproic acid, Xanthine, 3-Phenyilactic acid, Azelaic acid, Apro barbital, Decosahexaenoic acid, Methil hydrogen Phenylphoshonate, (1S)-1-Carboxy-N,N,N-trimethyl-2-(2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethanaminium, D-(+)-Tryptophan, uracil, ?17-6-keto Prostaglandin F1, Hypoxanthine, 20-hydroxy Prostaglandin F2?, 2-Hydroxy-4-methylthiobutanoic acid, N-(2-Furylmethyl)-3-[(2S,5aS,8aR)-1-methyl-5-oxodecahydropyrrolo[3,2-E][1,4]diazepin-2-yl]propanamide, 6-Hydroxycaproic acid, Methaphenilene, 15(S)-HpEPE, [(4Z)-5-(Methylsulfanyl)-4-penten-2-yn-1-yl]benzene, Suberic acid.

Advances in the Pathogenesis and Treatment of Rosacea: A Phenotype-Based Therapeutic Approach

Rosacea is a common chronic inflammatory skin disorder that mainly affects the central face. It is primarily characterized by recurrent episodes of flushing, persistent erythema, inflammatory papules, telangiectasias, phymatous changes, and ocular symptoms. Its pathogenesis is complex and still not completely understood. It encompasses innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. To date, four subtypes of rosacea have been identified, based on the predominant clinical features: erythemato-teleangiectatic, papulopustular, pyhomatous, and ocular rosacea. New insights into this condition have led to several pharmacological treatments, including topical medications, spanning from the conventional azelaic acid, metronidazole, benzoyl peroxide, clindamycin, and erythromycin to new ones including not only brimonidine, oxymetazoline, ivermectine, and minocycline but also systemic drugs such as oral antibiotics, isotretinoin, non-selective β-blockers or α2-adrenergic agonists, and laser- or light-based therapies, together with new therapeutic approaches. The aim of this study was to review the current literature on the pathophysiology of rosacea and to provide an overview of therapeutic approaches that specifically address each clinical subtype.

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid.

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a 'C4-TRAP transporter', and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10-9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid

Photosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism, and toxicity of Aze on two microalgal-associated bacteria, Phycobacter and Alteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source. Phycobacter took up Aze at an initial uptake rate of 3.8×10–9 nmol/cell/hr and utilized it as a carbon source in concentrations ranging from 10 μM to 1 mM, suggesting a broad range of acclimation to Aze availability. For growth-impeded bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolize Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.

Peptide and peptidomimetic tyrosinase inhibitors.

Melanin, which is produced by melanocytes and spread over keratinocytes, is responsible for human skin browning. There are several processes involved in melanogenesis, mostly prompted by enzymatic activities. Tyrosinase (TYR), a copper containing metalloenzyme, is considered the main actor in melanin production, as it catalyzes two crucial steps that modify tyrosine residues in dopaquinone. For this reason, TYR inhibition has been exploited as a possible mechanism of modulation of hyper melanogenesis. There are various types of molecules used to block TYR activity, principally used as skin whitening agents in cosmetic products, e.g., tretinoin, hydroquinone, azelaic acid, kojic acid, arbutin and peptides. Peptides are highly valued for their versatile nature, making them promising candidates for various functions. Their specificity often leads to excellent safety, tolerability, and efficacy in humans, which can be considered their primary advantage over traditional small molecules. There are several examples of tyrosinase inhibitor peptides (TIPs) operating as possible hypo-pigmenting agents, which can be classified according to their origin: natural, hybrid or synthetically produced. Moreover, the possibility of variating their backbones, introducing non-canonical amino acids or modifying one or more peptide bond(s), to obtain peptidomimetic molecules, is an added value to avoid or delay proteolytic activity, while the possibility of conjugation with other bioactive peptides or organic moieties can bring other specific activity leading to dual-functional peptides.

Study on the inhibitory mechanism of fig leaf extract against postharvest Fusarium in melon.

The fungistaticity of fig leaf extract were analyzed by the ring of inhibition method. Fusarium equiseti was selected as the target for analyzing its fungistatic mechanism in terms of mycelial morphology, ultrastructure, cell membrane permeability, membrane plasma peroxidation, reactive oxygen species (ROS) content and changes in the activity of protective enzymes. The effect of this extract was verified in melon, and its components were determined by metabolite analysis using ultraperformance liquid chromatography‒mass spectrometry (UPLC‒MS). Fig leaf extract had an obvious inhibitory effect on Fusarium, and the difference was significant (P < 0.05) or highly significant (P < 0.01). Scanning and transmission electron microscopy revealed that F. equiseti hyphae exhibited obvious folding, twisting and puckering phenomena, resulting in an increase in the cytoplasmic leakage of spores, interstitial plasma, and the concentration of the nucleus, which seriously damaged the integrity of the fungal cell membrane. This phenomenon was confirmed by propidium iodide (PI) and fluorescein diacetate (FAD) staining, cell membrane permeability and malondialdehyde (MDA) content. Fig leaf extract also induced the mycelium to produce excessive H2O2,which led to lipid peroxidation of the cell membrane, promoted the accumulation of MDA, accelerated protein hydrolysis, induced an increase in antioxidant enzyme activity, and disrupted the balance of ROS metabolism; these findings showed that fungal growth was inhibited, which was verified in melons. A total of 1,540 secondary metabolites were detected by broad-targeted metabolomics, among which the fungistatic active substances flavonoids (15.45%), phenolic acids (15%), and alkaloids (10.71%) accounted for a high percentage and the highest relative content of these substances 1,3,7,8-tetrahydroxy-2- prenylxanthone, 8-hydroxyquinoline and Azelaic acid were analysed for their antimicrobial, anti-inflammatory, antioxidant, preventive effects against plant diseases and acquisition of resistance by plants. This confirms the reason for the fungicidal properties of fig leaf extracts. Fig leaf extract has the potential to be developed into a plant-derived fungicide as a new means of postharvest pathogen prevention and control in melon.

Stilbenes-enriched peanut sprouts alleviated physical fatigue via regulating interactions of nutrients-microbiota-metabolites revealed by multi-omics analysis.

In this study, the antifatigue effect and mechanism of peanut sprouts were explored. BALB/c mice divided into three groups (control, dark and UV-C) were respectively supplemented with a normal diet, peanut sprouts (dark germination) added diet and stilbenes-enriched peanut sprouts (UV-C radiated germination) added diet. Results showed that swimming time and levels of blood glucose and antioxidant enzymes significantly increased, while contents of triglyceride and malondialdehyde notably decreased by peanut sprout supplementation. Besides, combined analysis of gut microbiota gene sequencing and targeted metabolomics of fecal metabolites revealed that peanut sprout supplementation up-regulated abundances and metabolic transformations of Catenibacillus, Odoribacter, Prevotellaceae-UCG-001 and Butyricicoccus while it down-regulated the abundance of Parabacteroides. Consequently, contents of sebacic acid, azelaic acid, suberic acid, heptanoic acid, pimelic acid, aminoadipic acid and mono-phenolics notably increased, which were markedly correlated with the antifatigue effect. Compared with the dark group, the swimming time, glutathione peroxidase activity, methylmalonylcarnitine content and abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 were higher in the UV-C group, while opposite results were obtained for the levels of triglyceride, malondialdehyde, alpha-linolenic acid, gamma-linolenic acid, 10Z-heptadecenoic acid and palmitelaidic acid. Overall, peanut sprout supplementation could alleviate fatigue by modulating gut microbiota composition to promote fatty acid oxidation and lysine and stilbene catabolism to increase energy supply and regulate redox balance. UV-C-radiated peanut sprout supplementation could alleviate fatigue more effectively by up-regulating abundances of Butyricicoccus, Catenibacillus and Lachnospiraceae NK4A136 to promote long-chain fatty acid oxidation and catabolism of flavonoids and stilbenes efficiently.

Medium-chain dicarboxylic acids: chemistry, pharmacological properties, and applications in modern pharmaceutical and cosmetics industries.

Succinic (SUA), glutaric (GLA), pimelic (PA), suberic (SUBA), adipic (ADA), azelaic (AZA), and sebacic acids (SA) make up the majority of medium-chain dicarboxylic acids (MCDAs) with chain lengths of C4-C10, and are widely utilised in the chemical, food, textile, pesticide, pharmaceutical, and liquid crystal sectors. The MCDAs' two carboxyl groups provide them with an incredibly broad variety of applications. The focus of significant scientific research now is on the increasingly varied pharmacological effects of MCDAs. However, only a few studies have compared the biological characteristics of MCDAs in the contemporary pharmaceutical and cosmetic sectors and thoroughly examined the most recent research and marketing initiatives for MCDAs. This review's objective is to offer a thorough analysis of academic works on MCDAs, to assess the usefulness of these substances' chemical-pharmacological properties for use in the contemporary pharmaceutical and cosmetic industries, and to investigate the direction of their possible applications in these two disciplines. In addition, this review investigates how these compounds are metabolised in the human body.

Acneiform eruptions associated with nintedanib – A case report

Interstitial lung diseases (ILDs) these are a group of diffuse parenchymal lung disorders present with increased risk of morbidity and mortality. The patient presents with symptoms of gradual onset of dyspnea, dry cough, chest discomfort, and extreme tiredness, which causes decreased quality of life. Treatment of ILD includes the use of immunomodulatory therapies such as corticosteroids, azathioprine, cyclophosphamide, and monoclonal antibodies. Antifibrotic therapies include the use of pirfenidone and nintedanib. The most common adverse effects associated with tyrosine kinase inhibitors include hepatotoxicity, hypertension, Steven–Johnson syndrome, acne-like skin rash, and pruritus. The patient presented to the dermatology outpatient department with complaints of acneiform eruptions over the forehead and cheeks. Lesions started within 7–15 days of starting nintedanib for ILD. Post-dermatology consultation and local examination, acneiform eruptions due to the drug are the probable diagnosis made, and therefore, capsule nintedanib was withheld and prescribed Vitamin C tablets, tretinoin 0.05% with azelaic acid 10% and sunscreen. At the time of discharge tapering doses of prednisolone, tablet deriphylline 150 mg BD and tablet n-acetyl-cysteine 600 mg BD for 14 days were prescribed. Detailed history of the patient was taken and the relevant medical documents were scrutinized. This case was assessed as per the pharmacovigilance program of India. A very rare adverse reaction was seen with the use of nintedanib. After discontinuation of capsule nintedanib and acne management, patient experienced an improvement in the acne lesions. The case reported is a very rare adverse reaction seen with the use of nintedanib for the management of ILD. Our study is supported by temporal association, biological plausibility, and successful de-challenge.

Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients.

Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should not be overlooked. Drug-based therapy requires time to be personalized and to evaluate the benefit/risk ratio. However, the increasing number of diagnosed UC cases worldwide necessitates the exploration of new strategies to enhance clinical outcomes. By incorporating medical devices alongside pharmacological treatments, clinicians can provide additional support to UC patients, potentially improving their condition and slowing down the recurrence of symptoms. Chemically identified as an azelaic acid derivative and palmitoylethanolamide (PEA) analog, adelmidrol is a potent anti-inflammatory and antioxidant compound. In this study, we aimed to evaluate the effect of an intrarectal administration of 2% adelmidrol (Ade) and 0.1% hyaluronic acid (HA) gel formulation in both the acute and resolution phase of a mouse model of colitis induced via DNBS enema. We also investigated its activity in cultured human colon biopsies isolated from UC patients in the remission phase at follow-up when exposed in vitro to a cytomix challenge. Simultaneously, with its capacity to effectively alleviate chronic painful inflammatory cystitis when administered intravesically to urological patients such as Vessilen, the intrarectal administration of Ade/HA gel has shown remarkable potential in improving the course of colitis. This treatment approach has demonstrated a reduction in the histological damage score and an increase in the expression of ZO-1 and occludin tight junctions in both in vivo studies and human specimens. By acting independently on endogenous PEA levels and without any noticeable systemic absorption, the effectiveness of Ade/HA gel is reliant on a local antioxidant mechanism that functions as a "barrier effect" in the inflamed gut. Building on the findings of this preliminary study, we are confident that the Ade/HA gel medical device holds promise as a valuable adjunct in supporting traditional anti-UC therapies.

Exploration of Variable Solvent Directed Self-Healable Supramolecular M(II)-Metallogels (M = Co, Ni, Zn) of Azelaic Acid: Investigating Temperature-Dependent Ion Conductivity and Antibacterial Efficiency.

Molecular self-assembly assisted self-healing supramolecular metallogels of azelaic acid with cobalt(II)-, nickel(II)-, and zinc(II)-based metal acetate salts were successfully fabricated. Individually, N,N'-dimethylformamide and dimethyl sulfoxide were immobilized within these distinctly synthesized soft-scaffolds of metallogels to attain their semisolid viscoelastic nature. Rheological experiments such as amplitude sweep, frequency sweep, and thixotropic measurements were executed for these metallogels to ratify their gel features. The different extents of supramolecular interactions operating within these solvent-directed metallogels were clearly reflected in terms of their distinct morphological patterns as investigated through field emission scanning electron microscopy. Comparative infrared (IR) spectral properties of metallogels along with individual metal salts and azelaic acid were analyzed. These experimental data clearly depict the significant shifting of Fourier transform (FT)-IR peaks of xerogel samples of different metallogels from the gel-forming precursors. The networks present within the soft-scaffold are evidently illustrated by the electrospray ionization-mass experimental data. The temperature-dependent ionic conductivity studies with these solvent-directed versatile metallogel systems were investigated through impedance spectroscopy. The temperature-dependent impedance spectroscopic studies clearly demonstrate that the ion-transportation within the gel matrix depends not only on the types of cations but also on the dielectric properties of the immobilized solvents. The antipathogenic effect of these metallogel systems has also been explored by testing their effectiveness against human pathogenic Gram-negative bacteria Klebsiella pneumoniae (MTCC 109) and Vibrio parahemolyticus, and Gram-positive bacteria like Bacillus cereus (MTCC 1272). These gel soft-scaffolds show no significant cytotoxicity against both the human neuroblastoma cell line-SH-SY5Y and the human embryonic kidney cell line-HEK 293.

Genetic mutation and aqueous humor metabolites alterations in a family with Marfan syndrome

This study used four generations of a Chinese family to reveal the genetic etiology and ocular manifestation pathogenesis of Marfan syndrome (MFS) through whole genome sequencing (WGS) and metabolomics analysis. In the study, we explored the pathogenic gene variant and aqueous humor (AH) metabolites alterations of MFS. Using WGS, a novel heterozygous variant (NM_000138: c.G4192A, p.D1398 N) in the fibrilin-1 (FBN1) gene was identified. This variant was co-segregated with the phenotype and considered “deleterious” and highly conserved during evolution. The p.D1398 N variant is located in a cbEGF-like domain and predicted to lead to a new splice site, which might result in structural and functional changes to the FBN1 protein. FBN1 is highly expressed in the mouse cornea, conjunctiva and lens capsule, which highlights the important role of FBN1 in eyeball development. AH metabolomics analysis identified eight differentially expressed metabolites, including 3-hydroxyphenylacetic acid, 4-pyridoxic acid, aminoadipic acid, azelaic acid, chlordiazepoxide, niacinamide, ribose, 1,5-bisphosphate and se-methylselenocysteine, associated with relevant metabolic pathways likely involved in the pathogenesis of ocular symptoms in MFS. Our analysis extends the existing spectrum of disease-causing mutations and reveals metabolites information related to the ophthalmic features of MFS. This may provide a new sight and a basis for the diagnosis and mechanism of MFS.

Gut microbiota-related metabolite alpha-linolenic acid mitigates intestinal inflammation induced by oral infection with Toxoplasma gondii

BackgroundOral infection with cysts is the main transmission route of Toxoplasma gondii (T. gondii), which leads to lethal intestinal inflammation. It has been widely recognized that T. gondii infection alters the composition and metabolism of the gut microbiota, thereby affecting the progression of toxoplasmosis. However, the potential mechanisms remain unclear. In our previous study, there was a decrease in the severity of toxoplasmosis after T. gondii α-amylase (α-AMY) was knocked out. Here, we established mouse models of ME49 and Δα-amy cyst infection and then took advantage of 16S rRNA gene sequencing and metabolomics analysis to identify specific gut microbiota-related metabolites that mitigate T. gondii-induced intestinal inflammation and analyzed the underlying mechanism.ResultsThere were significant differences in the intestinal inflammation between ME49 cyst- and Δα-amy cyst-infected mice, and transferring feces from mice infected with Δα-amy cysts into antibiotic-treated mice mitigated colitis caused by T. gondii infection. 16S rRNA gene sequencing showed that the relative abundances of gut bacteria, such as Lactobacillus and Bacteroides, Bifidobacterium, [Prevotella], Paraprevotella and Macellibacteroides, were enriched in mice challenged with Δα-amy cysts. Spearman correlation analysis between gut microbiota and metabolites indicated that some fatty acids, including azelaic acid, suberic acid, alpha-linolenic acid (ALA), and citramalic acid, were highly positively correlated with the identified bacterial genera. Both oral administration of ALA and fecal microbiota transplantation (FMT) decreased the expression of pro-inflammatory cytokines and restrained the MyD88/NF-κB pathway, which mitigated colitis and ultimately improved host survival. Furthermore, transferring feces from mice treated with ALA reshaped the colonization of beneficial bacteria, such as Enterobacteriaceae, Proteobacteria, Shigella, Lactobacillus, and Enterococcus.ConclusionsThe present findings demonstrate that the host gut microbiota is closely associated with the severity of T. gondii infection. We provide the first evidence that ALA can alleviate T. gondii-induced colitis by improving the dysregulation of the host gut microbiota and suppressing the production of pro-inflammatory cytokines via the MyD88/NF-κB pathway. Our study provides new insight into the medical application of ALA for the treatment of lethal intestinal inflammation caused by Toxoplasma infection.5uvpHNDACknu2usY1bpcjuVideo

Efficacy and Safety of Topical 5% Azelaic Acid Solution Versus 2% Minoxidil Solution in the Treatment of Female Pattern Hair Loss

Objective: To determine the efficacy and safety of 5% azelaic acid solution in comparison with 2% minoxidil solution in the treatment of FPHL. Materials and Methods: Twenty-six FPHL patients with Ludwig grade I or II were randomly treated with 5% azelaic acid solution or 2% minoxidil solution twice daily for 6 months. At baseline, 2, 4, and 6 months, hair density and hair shaft diameter were assessed at the targeted fixed area. At 6 months, patient and investigator assessments of hair growth were performed using a 7-point scale. Results: Hair density and hair shaft diameter in the patients treated with 5% azelaic acid and 2% minoxidil solution were significantly increased compared to the baseline in all cases and visits (P &lt; 0.05). There were no statistically significant differences in hair density and hair shaft diameter changes between both groups (P &gt; 0.05). Both the investigator and patient assessments were comparable between both groups at 6 months. Pruritus was the major adverse effect reported in both groups, but only mild and all could be tolerated. Conclusion: 5% Azelaic acid solution might be an effective treatment for FPHL, comparable with 2% minoxidil, and could be an alternative treatment for FPHL in minoxidil-allergic patients and pregnant women.