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BioRxiv : the Preprint Server For... May 2024causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the...
causes life-threatening infections that are becoming difficult to treat due to increasing rates of multi-drug resistance (MDR) among clinical isolates. This has led the World Health Organization and the CDC to categorize MDR as a top priority for the research and development of new antibiotics. Colistin is the last-resort antibiotic to treat carbapenem-resistant . Not surprisingly, reintroduction of colistin has resulted in the emergence of colistin-resistant strains. Diclofenac is a nonsteroidal anti-inflammatory drug used to treat pain and inflammation associated with arthritis. In this work, we show that diclofenac sensitizes colistin-resistant clinical strains to colistin, and in a murine model of pneumonia. Diclofenac also reduced the colistin MIC of and isolates. Transcriptomic and proteomic analyses revealed an upregulation of oxidative stress-related genes and downregulation of type IV pili induced by the combination treatment. Notably, the concentrations of colistin and diclofenac effective in the murine model were substantially lower than those determined , implying a stronger synergistic effect compared to . A mutant strain, lacking the primary component of the type IV pili, became sensitive to colistin in the absence of diclofenac. This suggest that the downregulation of type IV pili is key for the synergistic activity of these drugs and indicates that colistin and diclofenac exert an anti-virulence effect. Together, these results suggest that the diclofenac can be repurposed with colistin to treat MDR .
PubMed: 38798593
DOI: 10.1101/2024.05.17.594771 -
Chemosphere Jul 2024In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two...
In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two pollutants on grass carp under single and combined exposure are unknown. In this study, the concentrations of pollutants in different tissues were detected, and the toxicities of the two pollutants to grass carp under different exposure conditions were compared based on growth traits, biochemical responses, gut microbiome, and transcriptomes. Based on these findings, the brain showed the lowest levels of Cd and DCF accumulation. Oxidative stress and pathological damage were observed in the brain and intestines. Changes in the structure and abundance of the gut microflora affect the synthesis of neurotransmitters, such as GABA and steroids. Differentially expressed genes in the brain were enriched in circadian rhythm functions. The expression of PER, CLOCK,1L-1β, 1L-17, and other genes are related to the abundance of Akkermansia, which indicates that the disorder of gut microflora will affect the normal circadian rhythm of the brain. All indices in the recovery group showed an increasing trend. Overall, the toxicity of Cd and DCF showed antagonism, and a single exposure had a stronger effect on gut microorganisms and circadian rhythm, which provided a scientific basis for exploring the comprehensive effects of different pollutants.
Topics: Animals; Carps; Gastrointestinal Microbiome; Cadmium; Water Pollutants, Chemical; Diclofenac; Transcriptome; Oxidative Stress; Brain
PubMed: 38797211
DOI: 10.1016/j.chemosphere.2024.142428 -
International Journal of Biological... Jun 2024Metal-organic frameworks are emerging inorganic-organic hybrid materials that can be self-assembled from metal ions and organic ligands via coordination bonds. These...
Metal-organic frameworks are emerging inorganic-organic hybrid materials that can be self-assembled from metal ions and organic ligands via coordination bonds. These materials possess large specific surface area, tunable pore structure, abundant active center, diversity of functional groups as well as high mechanical and thermal stability which promote their applications in adsorption and catalysis studies. In this study, NH-MIL-53(Al/Zr) was prepared and embedded into sodium alginate gel spheres (NH-MIL-53(Al/Zr)-SA) and its adsorption properties towards TC and DCF in solution were investigated. According to XRD and FTIR analysis, the structure of the raw material was not changed after making the gel spheres. The maximum adsorption towards TC (pH =3) and DCF (pH =5) reached 98.5 mg·g and 192 mg·g, respectively. The process was consistent with Langmuir and Freundlich, suggesting that there was both monolayer and multilayer adsorption which infers the presence of physical adsorption (intra-particle diffusion) and non-homogeneous chemical adsorption. The thermodynamic parameters showed that the adsorption process was a spontaneous entropy increasing reaction. The regeneration rate of spent NH-MIL-53(Al/Zr)-SA could still reach 99.1 % after three cycles, indicating good regeneration performance. This study can provide a basis for the application of NH-MIL-53(Al/Zr)-SA in wastewater treatment.
Topics: Alginates; Adsorption; Diclofenac; Metal-Organic Frameworks; Tetracycline; Gels; Water Pollutants, Chemical; Thermodynamics; Water Purification; Kinetics; Hydrogen-Ion Concentration; Zirconium
PubMed: 38795565
DOI: 10.1016/j.ijbiomac.2024.132637 -
International Journal of... May 2024This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl (ZnCl-RS) for the removal of diclofenac sodium (DCF) and paracetamol...
This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl (ZnCl-RS) for the removal of diclofenac sodium (DCF) and paracetamol (PCM) through an adsorption process. The investigation included examining the variations in removal efficiency at different pH levels and ZnCl-RS doses. The characteristics of the ZnCl-RS, prepared for the study, were determined through SEM and FTIR analyses, revealing a composition of 49.4% carbon and 8.3% zinc. At pH 5, the adsorption efficiency for DCF and PCM was enhanced, achieving removal rates of 92.2% for DCF and 89.1% for PCM with 0.2 g of ZnCl-RS. The adsorption of DCF and PCM by ZnCl-RS followed pseudo-second-order kinetic and adhered to the Langmuir isotherm model. The maximum adsorption capacities were calculated as 26.04 mg/g for DCF and 19.05 mg/g for PCM. In conclusion, the cost-effective production of activated carbon from agricultural waste like rice straw yielded a promising adsorbent material for efficiently removing pharmaceuticals such as diclofenac sodium and paracetamol. This approach not only contributes to waste reduction but also promotes the repurposing of agricultural waste materials.
PubMed: 38794784
DOI: 10.1080/15226514.2024.2357644 -
Pharmaceuticals (Basel, Switzerland) May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.
PubMed: 38794197
DOI: 10.3390/ph17050627 -
Materials (Basel, Switzerland) May 2024The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this...
The global presence of pharmaceutical pollutants in water sources represents a burgeoning public health concern. Recent studies underscore the urgency of addressing this class of emerging contaminants. In this context, our work focuses on synthesizing a composite material, FeO/MAF-32, through a streamlined one-pot reaction process, as an adsorbent for diclofenac, an emerging environmental contaminant frequently found in freshwater environments and linked to potential toxicity towards several organisms such as fish and mussels. A thorough characterization was performed to elucidate the structural composition of the composite. The material presents magnetic properties attributed to its superparamagnetic behavior, which facilitates the recovery efficiency of the composite post-diclofenac adsorption. Our study further involves a comparative analysis between the FeO/MAF-32 and a non-magnetic counterpart, comprised solely of 2-ethylimidazolate zinc polymer. This comparison aims to discern the relative advantages and disadvantages of incorporating magnetic iron oxide nanoparticles in the contaminant removal process facilitated by a coordination polymer. Our findings reveal that even a minimal incorporation of iron oxide nanoparticles substantially enhanced the composite's overall performance in pollutant adsorption.
PubMed: 38793334
DOI: 10.3390/ma17102269 -
Medicina (Kaunas, Lithuania) May 2024: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation,...
: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. : We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp () and cultured in vitro, as well as their effects on the expression of angiogenic growth factors ( and ) and selected genes in apoptosis signalling pathways (, , , , and 2). : Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of , while the expression of remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of and , with decreased expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. : Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.
Topics: Humans; Dental Pulp; Diclofenac; Apoptosis; Ibuprofen; Cell Survival; Anti-Inflammatory Agents, Non-Steroidal; Stem Cells; Mesenchymal Stem Cells; Cells, Cultured
PubMed: 38792973
DOI: 10.3390/medicina60050787 -
Molecules (Basel, Switzerland) May 2024CYP2A7 is one of the most understudied human cytochrome P450 enzymes and its contributions to either drug metabolism or endogenous biosynthesis pathways are not...
CYP2A7 is one of the most understudied human cytochrome P450 enzymes and its contributions to either drug metabolism or endogenous biosynthesis pathways are not understood, as its only known enzymatic activities are the conversions of two proluciferin probe substrates. In addition, the CYP2A7 gene contains four single-nucleotide polymorphisms (SNPs) that cause missense mutations and have minor allele frequencies (MAFs) above 0.5. This means that the resulting amino acid changes occur in the majority of humans. In a previous study, we employed the reference standard sequence (called CYP2A7*1 in P450 nomenclature). For the present study, we created another CYP2A7 sequence that contains all four amino acid changes (Cys311, Glu169, Gly479, and Arg274) and labeled it CYP2A7-WT. Thus, it was the aim of this study to identify new substrates and inhibitors of CYP2A7 and to compare the properties of CYP2A7-WT with CYP2A7*1. We found several new proluciferin probe substrates for both enzyme variants (we also performed in silico studies to understand the activity difference between CYP2A7-WT and CYP2A7*1 on specific substrates), and we show that while they do not act on the standard CYP2A6 substrates nicotine, coumarin, or 7-ethoxycoumarin, both can hydroxylate diclofenac (as can CYP2A6). Moreover, we found ketoconazole, 1-benzylimidazole, and letrozole to be CYP2A7 inhibitors.
Topics: Humans; Substrate Specificity; Aryl Hydrocarbon Hydroxylases; Enzyme Inhibitors; Polymorphism, Single Nucleotide
PubMed: 38792050
DOI: 10.3390/molecules29102191 -
International Journal of Biological... Jun 2024The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro...
Fabrication and optimization of extended-release beads of diclofenac sodium based on Ca cross-linked Taro (Colocasia esculenta) stolon polysaccharide and pectin by quality-by-design approach.
The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro (Colocasia esculenta) stolon polysaccharide (TSP) with 2 full factorial design. Total polysaccharide concentration (TPC), polysaccharide ratio (PR), and cross-linker concentration ([CaCl]) were taken as independent factors with two levels of each. Initially, TSP was extracted, purified, and characterized. Fourier-transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed drug-polymer compatibility. The study also revealed the significant positive effect of TSP on drug entrapment efficiency (DEE) and sustaining drug release. The response variables (DEE, cumulative % drug-release at 1, 2, 4, 6, and 10 h, release-constant, time for 50 % and 90 % drug release (T, T), release-similarity factor (f), and difference factor (f) were analyzed, and subsequently, independent fabrication variables were numerically optimized by Design-Expert software (Version-13; Stat-Ease Inc., Minneapolis). The optimized batch exhibited appreciable DEE of 88.5 % (± 2.2) and an extended-release profile with significantly higher T, T, and release-similarity factor (f) of 4.7 h, 11.4 h, and 71.6, respectively. Therefore, the study exhibited successful incorporation of the novel TSP as a potential alternative adjunct polysaccharide in the pectin-based ion-cross-linked inter-penetrating polymeric network for extended drug release.
Topics: Diclofenac; Pectins; Delayed-Action Preparations; Drug Liberation; Colocasia; Drug Carriers; Polysaccharides; Calcium; Microspheres; Spectroscopy, Fourier Transform Infrared
PubMed: 38788875
DOI: 10.1016/j.ijbiomac.2024.132606 -
Journal of Cutaneous Medicine and... May 2024Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod.... (Review)
Review
BACKGROUND/OBJECTIVES
Actinic keratoses (AK) are premalignant skin lesions caused by chronic sun exposure, topically managed by 5-fluorouracil (5-FU), diclofenac 3% gel, and imiquimod. Despite their effectiveness, long treatment duration and severe adverse local skin reactions have limited patient concordance. Calcipotriol has recently been used as a combination agent for existing topical AK treatments. A systematic review was performed to determine the clinical efficacy of 5-FU and calcipotriol for the treatment of AK, Bowen's disease, and squamous cell carcinoma (SCC).
METHODS
A systematic literature search was conducted on Medline, Embase, and Cochrane Library. Among the 84 records screened, 12 were retrieved for full-text review and 8 were included in the final analysis.
RESULTS
Among the 8 studies, there were 214 control patients and 288 patients who received the intervention. The combination 5% 5-FU with calcipotriol resulted in a significant reduction in the number of AKs on the face, scalp, right upper extremity, and left upper extremity for all sites at 8 weeks ( < .0001). No significant difference in SCC incidence was observed at 1 or 2 years, but there was a significant reduction observed at 3 years for SCC on face and scalp. No study assessed the combination for Bowen's disease.
CONCLUSIONS
Combination 5% 5-FU with calcipotriol is an effective treatment for Aks; however, future trials may consider longer treatment and follow-up periods for the treatment and prevention of AK, SCC in situ, and SCC.
PubMed: 38783539
DOI: 10.1177/12034754241256347