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Angewandte Chemie (International Ed. in... Nov 2023The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to...
The development of Alzheimer's disease (AD) drugs has recently witnessed substantial achievement. To further enhance the pool of drug candidates, it is crucial to explore non-traditional therapeutic avenues. In this study, we present the use of a photolabile curcumin-diazirine analogue, CRANAD-147, to induce changes in properties, structures (sequences), and neurotoxicity of amyloid beta (Aβ) species both in cells and in vivo. This manipulation was achieved through irradiation with LED light or molecularly generated light, dubbed as "molecular light", emitted by the chemiluminescence probe ADLumin-4. Next, aided by molecular chemiluminescence imaging, we demonstrated that the combination of CRANAD-147/LED or CRANAD-147/ADLumin-4 (molecular light) could effectively slow down the accumulation of Aβs in transgenic 5xFAD mice in vivo. Leveraging the remarkable tissue penetration capacity of molecular light, phototherapy employing the synergistic effect of a photolabile Aβ ligand and molecular light emerges as a promising alternative to conventional AD treatment interventions.
Topics: Mice; Animals; Alzheimer Disease; Amyloid beta-Peptides; Curcumin; Diazomethane; Mice, Transgenic; Phototherapy; Disease Models, Animal
PubMed: 37721455
DOI: 10.1002/anie.202312519 -
Ecotoxicology and Environmental Safety Sep 2023The presence of high salinity levels in textile wastewater poses a significant obstacle to the process of decolorizing azo dyes. The present study involved the...
The presence of high salinity levels in textile wastewater poses a significant obstacle to the process of decolorizing azo dyes. The present study involved the construction of a yeast consortium HYC, which is halotolerant and was recently isolated from wood-feeding termites. The consortium HYC was mainly comprised of Sterigmatomyces halophilus SSA-1575 and Meyerozyma guilliermondii SSA-1547. The developed consortium demonstrated a decolourization efficiency of 96.1% when exposed to a concentration of 50 mg/l of Reactive Black 5 (RB5). The HYC consortium significantly decolorized RB5 up to concentrations of 400 mg/l and in the presence of NaCl up to 50 g/l. The effects of physicochemical factors and the degradation pathway were systematically investigated. The optimal pH, salinity, temperature, and initial dye concentration were 7.0, 3%, 35 °C and 50 mg/l, respectively. The co-carbon source was found to be essential, and the addition of glucose resulted in a 93% decolorization of 50 mg/l RB5. The enzymatic activity of various oxido-reductases was assessed, revealing that NADH-DCIP reductase and azo reductase exhibited greater activity in comparison to other enzymes. UV-Visible (UV-vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS) were utilized to identify the metabolites generated during the degradation of RB5. Subsequently, a metabolic pathway was proposed. The confirmation of degradation was established through alterations in the functional groups and modifications in molecular weight. The findings indicate that this halotolerant yeast consortium exhibits promising potential of degrading dye compounds. The results of this study offer significant theoretical basis and crucial perspectives for the implementation of halotolerant yeast consortia in the bioremediation of textile and hypersaline wastewater. This approach is particularly noteworthy as it does not produce aromatic amines.
Topics: Azo Compounds; Wastewater; Gas Chromatography-Mass Spectrometry; Chromatography, High Pressure Liquid; Biodegradation, Environmental; Coloring Agents
PubMed: 37478569
DOI: 10.1016/j.ecoenv.2023.115258 -
Frontiers in Immunology 2023Crohn's disease (CD) is a complex and poorly understood myeloid-mediated disorder. Genetic variants with loss of function in the gene confer an increased susceptibility...
BACKGROUND
Crohn's disease (CD) is a complex and poorly understood myeloid-mediated disorder. Genetic variants with loss of function in the gene confer an increased susceptibility to ileal CD. While Nod2 in myeloid cells may confer protection against T-cell mediated ileopathy, it remains unclear whether it may promote resolution of the inflamed colon. In this study, we evaluated the function of Nod2 in myeloid cells in a model of acute colitis and colitis-associated colon cancer (CAC).
METHODS
To ablate Nod2 specifically within the myeloid compartment, we generated mice. The role of NOD2 was studied in a setting of Dextran Sodium Sulfate (DSS)-induced colitis and in azoxymethane (AOM)/DSS model. Clinical parameters were quantified by colonoscopy, histological, flow cytometry, and qRT-PCR analysis.
RESULTS
Upon DSS colitis model, mice lost less weight than control littermates and had less severe damage to the colonic epithelium. In the AOM/DSS model, endoscopic monitoring of tumor progression revealed a lowered number of adenomas within the colon of mice, associated with less expression of . Mechanistically, lysozyme M was required for the improved disease severity in mice with a defect of NOD2 in myeloid cells.
CONCLUSION
Our results indicate that loss of Nod2 signaling in myeloid cells aids in the tissue repair of the inflamed large intestine through lysozyme secretion by myeloid cells. These results may pave the way to design new therapeutics to limit the inflammatory and tumorigenic functions of NOD2.
Topics: Animals; Mice; Azoxymethane; Colitis; Crohn Disease; Macrophages; Muramidase; Nod2 Signaling Adaptor Protein
PubMed: 37876927
DOI: 10.3389/fimmu.2023.1252979 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Aug 2023Azo dyes are widely used in textile, paper and packing industries, and have become one of the research hot spots in dye wastewater treatment because of their...
Azo dyes are widely used in textile, paper and packing industries, and have become one of the research hot spots in dye wastewater treatment because of their carcinogenicity, teratogenic mutagenicity, stable structure and degradation difficulty. In this study, the biodecolorization of acid orange 7 (AO7), an azo dye, by different white rot fungi was investigated, and the effect of different conditions on the decolorization rate of the dye was analyzed. At the same time, the degradation liquor was analyzed and the phytotoxicity experiment was performed to deduce the possible degradation pathway of AO7 and assess the toxicity of its degradation products. The results showed that the decolorization rate reached 93.46% in 24 h at pH 4.5, 28 ℃ by and when AO7 concentration was 100 mg/L. The biodegradation pathway of AO7 was initiated by the cleavage of the azo bond of AO7, generating p-aminobenzenesulfonic acid and 1-amino-2-naphthol. Subsequently, the sulfonic acid group of p-aminobenzene sulfonic acid was removed to generate hydroquinone. Moreover, the 1-amino-2-naphthol was de-ringed to generate phthalic acid and p-hydroxybenzaldehyde, and then further degraded into benzoic acid. Finally, hydroquinone and benzoic acid may be further oxidized into other small molecules, carbon dioxide and water. Phytotoxicity experiment showed that the toxicity of AO7 could be reduced by . and . .
Topics: Hydroquinones; Trametes; Azo Compounds; Benzoic Acid
PubMed: 37622371
DOI: 10.13345/j.cjb.220975 -
Organic Letters Sep 2023A base-mediated cascade reaction of CF-imidoyl sulfoxonium ylides and azo compounds has been achieved, allowing for facile access to trifluoromethyl-substituted...
A base-mediated cascade reaction of CF-imidoyl sulfoxonium ylides and azo compounds has been achieved, allowing for facile access to trifluoromethyl-substituted 1,2-dihydroquinoxalines and diimines in moderate to excellent yields. Noteworthy is that the unusual N-N bond cleavage and rearrangement of azo compounds are involved in the transformations.
PubMed: 37721372
DOI: 10.1021/acs.orglett.3c02718 -
Molecular Biology Reports Nov 2023Synthetic dyes are one of the main pollutants in the textile industry and bioremediation is considered as an environmentally friendly method to degrade them. Soil...
BACKGROUND
Synthetic dyes are one of the main pollutants in the textile industry and bioremediation is considered as an environmentally friendly method to degrade them. Soil microbial consortia (MCs) are reported having the potential of decolorizing most of textile dyes. This study aimed at evaluating dye-degrading ability of MCs developed from fungi and bacteria.
METHODS AND RESULTS
Fungi and bacteria were isolated from the soil samples obtained from textile waste dumping site at Horana industrial zone, Sri Lanka and were screened for crystal violet (CV) and congo red (CR) dyes to develop MCs. Decolorization assay was performed for MCs along with individual isolates under variable pH levels. Metabolized products were characterized to confirm the biodegradation. A. tamari (F5) and P. putida (B3) significantly (P < 0.05) decolorized both dyes. All the MCs showed higher decolorization percentages over the individual microorganisms. Neutral pH (pH 7) was the optimum pH for the decolorization of both dyes by individual isolates and the percentages were significantly changed under the acidic and basic pH levels. However, decolorization ability by all MCs was not significantly changed with pH. Consortium with A. tamari - P. putida significantly (P < 0.05) decolourized both dyes under optimum pH 7.
CONCLUSION
All MCs showed better pH tolerance in degrading CV and CR. Thus, it can be concluded that the selected MC with A. tamari - P. putida can degrade CV and CR textile dyes efficiently into non-toxic compounds against plants under neutral pH. Degradation and decolorization of textile azo dyes by effective fungal-bacterial consortium.
Topics: Azo Compounds; Coloring Agents; Congo Red; Biodegradation, Environmental; Bacteria; Textiles; Soil
PubMed: 37698753
DOI: 10.1007/s11033-023-08741-6 -
RSC Advances Dec 2023The objective of this study was to establish a novel method for the detection of lean meat powder (salbutamol sulfate and terbutaline sulfate) residues in commercially...
The objective of this study was to establish a novel method for the detection of lean meat powder (salbutamol sulfate and terbutaline sulfate) residues in commercially available pig liver based on diazo coupling reaction by combining thin layer chromatography (TLC) with surface-enhanced resonance Raman scattering (SERRS). TLC was used to separate samples; after determining the spots of each component, diazo coupling reaction was carried out on the spots in situ to generate azo compounds, and then the spots of azo compounds mixed with silver sol on the TLC plate were qualitatively detected by SERRS. The limit of detection (LOD) of salbutamol sulfate was as low as 0.14 μg kg, and that of terbutaline sulfate was as low as 0.04 μg kg. The influence of the sample matrix in TLC-SERRS detection of salbutamol sulfate and terbutaline sulfate was investigated by experiment on a simulated positive sample, and salbutamol sulfate and terbutaline sulfate in commercially available pig liver were detected. Compared with the reported method (HPLC-MS/MS), this method has the advantages of strong specificity, high sensitivity, rapidity and low cost. It provides a new reference method for establishing and perfecting the safety system of veterinary drug residues.
PubMed: 38090098
DOI: 10.1039/d3ra07202a -
Gut Microbes Dec 2023Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the...
Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice.
Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera and were more abundant in DY mice while the genera and were more abundant in DO mice. Amongst recipients, and were higher in RY mice while was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.
Topics: Mice; Animals; Azoxymethane; Gastrointestinal Microbiome; Microbiota; Fecal Microbiota Transplantation; Colonic Neoplasms; Inflammation; Carcinogenesis; Cell Proliferation
PubMed: 38031252
DOI: 10.1080/19490976.2023.2288187 -
Expert Opinion on Therapeutic Patents Dec 2023Schiff bases are compounds with characteristic features of azomethine linkage (-C=N-). Schiff bases are capable of coordinating with metal ions via azomethine nitrogen.... (Review)
Review
INTRODUCTION
Schiff bases are compounds with characteristic features of azomethine linkage (-C=N-). Schiff bases are capable of coordinating with metal ions via azomethine nitrogen. Schiff base derivatives and their metal complexes are known for intriguing novel therapeutic properties. In organic synthesis, the Schiff base reaction is prime in creating the C-N bond. Synthetic accessibility and structural diversity are the salient features for facile synthesis of Schiff base hybrids via a condensation reaction between an aldehyde/ketone and primary amines.
AREA COVERED
This review aims to provide a comprehensive overview of the commendable medicinal applications of Schiff base derivatives and their metal complexes patented from 2016 to 2023.
EXPERT OPINION
Schiff base derivatives are exceptional molecules for their assorted applications in medicinal chemistry. Several Schiff base products are marketed as drugs, and plenty of room is available for the purposive synthesis of new compounds in a diverse pool of disciplines. Expansion in the derivatization of Schiff bases in innumerable directions with multitudinous applications makes them 'magical molecules.' These compounds have proved extraordinary, from medicinal chemistry to other fields outside medicine. This review covers the therapeutic importance of Schiff base derivatives and aims to cover the patents published in recent years (2016-2023).
Topics: Humans; Coordination Complexes; Chemistry, Pharmaceutical; Schiff Bases; Patents as Topic; Ligands; Azo Compounds; Thiosemicarbazones
PubMed: 38115554
DOI: 10.1080/13543776.2023.2297729 -
Phytomedicine : International Journal... Mar 2024Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the...
BACKGROUND
Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known.
HYPOTHESIS/PURPOSE
We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux.
STUDY DESIGN
In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system.
METHODS
AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses.
RESULTS
Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1β inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNA regulated by osthole directly affects the cellular fate of colon cancer cells.
CONCLUSION
These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.
Topics: Mice; Animals; Calcium; Mitochondria; Colorectal Neoplasms; Azoxymethane; Autophagy; Dextran Sulfate; Coumarins
PubMed: 38295666
DOI: 10.1016/j.phymed.2024.155383