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European Archives of Psychiatry and... Oct 2023Schizophrenia is a psychiatric disorder characterised by symptoms in three domains: positive (e.g. delusions, hallucinations), negative (e.g. social withdrawal, lack of... (Review)
Review
Schizophrenia is a psychiatric disorder characterised by symptoms in three domains: positive (e.g. delusions, hallucinations), negative (e.g. social withdrawal, lack of motivation) and cognitive (e.g. working memory and executive function impairment). Cognitive impairment associated with schizophrenia (CIAS) is a major burden for patients and negatively impacts many aspects of a patient's life. Antipsychotics are the standard-of-care treatment for schizophrenia but only address positive symptoms. So far there are no approved pharmacotherapies for the treatment of CIAS. Iclepertin (BI 425809) is a novel, potent and selective glycine transporter 1 (GlyT1) inhibitor, under development by Boehringer Ingelheim for the treatment of CIAS. Phase I studies have shown it to be safe and well tolerated in healthy volunteers, and central target engagement (inhibition of GlyT1) was achieved in a dose-dependent manner from 5 to 50 mg in healthy volunteers. A Phase II study has demonstrated that iclepertin is safe and well tolerated in patients with schizophrenia and improves cognition at doses of 10 mg and 25 mg. Phase III studies are ongoing to confirm these initial positive safety and efficacy findings with the 10 mg dose, and if successful, iclepertin could become the first approved pharmacotherapy used to treat CIAS.
Topics: Humans; Schizophrenia; Glycine Plasma Membrane Transport Proteins; Cognitive Dysfunction; Organic Chemicals; Clinical Trials, Phase II as Topic
PubMed: 36971864
DOI: 10.1007/s00406-023-01576-z -
Nature Communications Sep 2023Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether...
Zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components affecting intestinal epithelial barrier function. Here, we explore whether zinc and the AHR pathway are linked. We show that dietary supplementation with an AHR pre-ligand offers protection against inflammatory bowel disease in a mouse model while protection fails in mice lacking AHR in the intestinal epithelium. AHR agonist treatment is also ineffective in mice fed zinc depleted diet. In human ileum organoids and Caco-2 cells, AHR activation increases total cellular zinc and cytosolic free Zn concentrations through transcription of genes for zinc importers. Tight junction proteins are upregulated through zinc inhibition of nuclear factor kappa-light-chain-enhancer and calpain activity. Our data show that AHR activation by plant-derived dietary ligands improves gut barrier function at least partly via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing inflammatory gut disorders.
Topics: Humans; Animals; Mice; Receptors, Aryl Hydrocarbon; Zinc; Caco-2 Cells; Ligands; Cytosol; Organic Chemicals
PubMed: 37669965
DOI: 10.1038/s41467-023-41168-y -
Theranostics 2023Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a...
Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect. We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system. ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD). The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM. The ZnMOF release profile and the penetration of ZnMOF-MN were also evaluated. The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs). Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing . Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining. ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm. ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn and curcumin. , ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency. In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration. Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models. Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.
Topics: Mice; Animals; Curcumin; Zinc; Ki-67 Antigen; Mice, Inbred C57BL; Hair; Alopecia; Drug Delivery Systems; Organic Chemicals
PubMed: 37441591
DOI: 10.7150/thno.84118 -
Molecules (Basel, Switzerland) Dec 2023Mechanochemical treatment of various organic molecules is an emerging technology of green processes in biofuel, fine chemicals, or food production. Many biopolymers are... (Review)
Review
Mechanochemical treatment of various organic molecules is an emerging technology of green processes in biofuel, fine chemicals, or food production. Many biopolymers are involved in isolating, derivating, or modifying molecules of natural origin. Mechanochemistry provides a powerful tool to achieve these goals, but the unintentional modification of biopolymers by mechanochemical manipulation is not always obvious or even detectable. Although modeling molecular changes caused by mechanical stresses in cavitation and grinding processes is feasible in small model compounds, simulation of extrusion processes primarily relies on phenomenological approaches that allow only tool- and material-specific conclusions. The development of analytical and computational techniques allows for the inline and real-time control of parameters in various mechanochemical processes. Using artificial intelligence to analyze process parameters and product characteristics can significantly improve production optimization. We aim to review the processes and consequences of possible chemical, physicochemical, and structural changes.
Topics: Artificial Intelligence; Chemical Phenomena; Biopolymers; Stress, Mechanical
PubMed: 38138521
DOI: 10.3390/molecules28248031 -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is an autoimmune disease and closely associated with both genetic and environmental factors. Volatile organic chemicals (VOC), a common...
INTRODUCTION
Rheumatoid arthritis (RA) is an autoimmune disease and closely associated with both genetic and environmental factors. Volatile organic chemicals (VOC), a common environment pollutant, was associated with some autoimmune diseases, while whether VOC exposure or which VOC leads to RA is yet clarified.
METHODS
A cross-sectional study using data from the 6 survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, 2017-2018, 2017-2020) of NHANES program was performed. The RA or non-arthritis status of participant was identified through a questionnaire survey. The quantile logistic regression method was used for correlation analysis between VOC metabolites (VOCs) in urine and RA. The covariates included age, gender, race, educational level, marital status, total energy intake, physical activity, smoking, hypertension, diabetes, urine creatinine, albumin and marihuana use.
RESULTS
A total of 9536 participants (aged 20 to 85) with 15 VOCs, comprising 618 RA and 8918 non-arthritis participants, was finally included for analysis. Participants in the RA group showed higher VOCs in urine than that in the non-arthritis group. A positive association between 2 VOCs (AMCC: Q4: OR=2.173, 95%CI: 1.021, 4.627. 3HPMA: Q2: OR=2.286, 95%CI: 1.207 - 4.330; Q4: OR=2.663, 95%CI: 1.288 -5.508.) and RA was detected in the model 3, which was independent of all the covariates. The relative parent compounds of the two VOCs included N,N-Dimethylformamide and acrolein.
DISCUSSION
These findings suggested that the VOC exposure significantly associated with RA, providing newly epidemiological evidence for the establishment that environmental pollutants associated with RA. And also, more prospective studies and related experimental studies are needed to further validate the conclusions of this study.
Topics: Humans; Volatile Organic Compounds; Cross-Sectional Studies; Nutrition Surveys; Prospective Studies; Arthritis, Rheumatoid; Environmental Pollutants
PubMed: 37404817
DOI: 10.3389/fimmu.2023.1098683 -
Plants (Basel, Switzerland) Oct 2023Essential oils (EOs) are concentrated hydrophobic liquids that originate from plants and contain different bioactive chemicals and volatile substances. Several plant...
Essential oils (EOs) are concentrated hydrophobic liquids that originate from plants and contain different bioactive chemicals and volatile substances. Several plant essential oils (PEOs) are obtained from a variety of medicinal plants and have been utilized in folk medicine and traditional pharmacopoeia. They have a long history of usage as antibacterial medicines to treat various human, animal, and plant diseases. The extraction of essential oils frequently involves fractional distillation with a variety of organic solvents. EOs can be used successfully in the food and cosmetics industries in addition to their traditional use as antimicrobial agents. This Special Issue covers various significant PEOs and their individual chemical constituents and biological-pharmaceutical functions. Further information focused on the chemical characterizations, modes of action, and biopharmaceutical properties of PEOs. This Special Issue includes seventeen research papers from different geographical zones.
PubMed: 37896079
DOI: 10.3390/plants12203616 -
International Journal of Molecular... Aug 2023In the last few decades, reticular chemistry has grown significantly as a field of porous crystalline molecular materials. Scientists have attempted to create the ideal... (Review)
Review
In the last few decades, reticular chemistry has grown significantly as a field of porous crystalline molecular materials. Scientists have attempted to create the ideal platform for analyzing distinct anions based on optical sensing techniques (chromogenic and fluorogenic) by assembling different metal-containing units with suitable organic linking molecules and different organic molecules to produce crystalline porous materials. This study presents novel platforms for anion recognition based on reticular chemistry with high selectivity, sensitivity, electronic tunability, structural recognition, strong emission, and thermal and chemical stability. The key materials for reticular chemistry, Metal-Organic Frameworks (MOFs), Zeolitic Imidazolate Frameworks (ZIFs), and Covalent-Organic Frameworks (COFs), and the pre- and post-synthetic modification of the linkers and the metal oxide clusters for the selective detection of the anions, have been discussed. The mechanisms involved in sensing are also discussed.
Topics: Anions; Oxides; Electronics; Metal-Organic Frameworks; Porosity
PubMed: 37685850
DOI: 10.3390/ijms241713045 -
Polymers Sep 2023Cellulose and hemicellulose are the main constituents of lignocellulosic biomass. Chemical derivatization of lignocellulosic biomass leads to a range of C5 and C6... (Review)
Review
Cellulose and hemicellulose are the main constituents of lignocellulosic biomass. Chemical derivatization of lignocellulosic biomass leads to a range of C5 and C6 organic compounds. These C5 and C6 compounds are valuable precursors (or fine chemicals) for developing sustainable chemical processes. Therefore, depolymerization of cellulose and hemicellulose is essential, leading to the development of various materials that have applications in biomaterial industries. However, most depolymerized processes for cellulose have limited success because of its structural quality: crystallinity, high hydrogen-bond networking, and mild solubility in organic and water. As a result, various chemical treatments, acidic (mineral or solid acids) and photocatalysis, have developed. One of the significant shortcomings of acidic treatment is that the requirement for high temperatures increases the commercial end cost (energy) and hampers product selectivity. For example, a catalyst with prolonged exposure to high temperatures damages the catalyst surface over time; therefore, it cannot be used for iterative cycles. Photocatalysts provide ample application to overcome such flaws as they do not require high temperatures to perform efficient catalysis. Various photocatalysts have shown efficient cellulosic biomass conversion into its C6 and C5 hydrocarbons and the production of hydrogen (as a green energy component). For example, TiO-based photocatalysts are the most studied for biomass valorization. Herein, we discussed the feasibility of a photocatalyst with application to cellulosic biomass hydrolysis.
PubMed: 37765525
DOI: 10.3390/polym15183671 -
Analytical and Bioanalytical Chemistry Jan 2024The human volatilome comprises a vast mixture of volatile emissions produced by the human body and its microbiomes. Following infection, the human volatilome undergoes... (Review)
Review
The human volatilome comprises a vast mixture of volatile emissions produced by the human body and its microbiomes. Following infection, the human volatilome undergoes significant shifts, and presents a unique medium for non-invasive biomarker discovery. In this review, we examine how the onset of infection impacts the production of volatile metabolites that reflects dysbiosis by pathogenic microbes. We describe key analytical workflows applied across both microbial and clinical volatilomics and emphasize the value in linking microbial studies to clinical investigations to robustly elucidate the metabolic species and pathways leading to the observed volatile signatures. We review the current state of the art across microbial and clinical volatilomics, outlining common objectives and successes of microbial-clinical volatilomic workflows. Finally, we propose key challenges, as well as our perspectives on emerging opportunities for developing clinically useful and targeted workflows that could significantly enhance and expedite current practices in infection diagnosis and monitoring.
Topics: Humans; Gas Chromatography-Mass Spectrometry; Volatile Organic Compounds
PubMed: 37843549
DOI: 10.1007/s00216-023-04986-z -
Advanced Science (Weinheim,... Oct 2023Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone... (Review)
Review
Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.
Topics: Osseointegration; Metal-Organic Frameworks; Titanium; Prostheses and Implants; Bone and Bones
PubMed: 37705110
DOI: 10.1002/advs.202303958