Review
Environmental Sciences
Aishwarya Rastogi, Manoj Kumar Tiwari, Makarand M. Ghangrekar
Summary: In recent years, NSAIDs have emerged as a new class of pollutants due to their incomplete degradation in wastewater treatment plants and potential physiological effects in humans even at low doses. Studies have shown that although NSAID concentrations in natural waters are typically low, untreated wastewater discharge can lead to higher concentrations, highlighting the importance of effective wastewater treatment. Furthermore, research has indicated that certain bacterial strains have the ability to degrade NSAIDs, emphasizing their crucial role in the degradation process.
JOURNAL OF ENVIRONMENTAL MANAGEMENT
(2021)
Article
Cell Biology
Roua Chaabani, Mohamed Bejaoui, Ikram Ben Jeddou, Mohamed Amine Zaouali, Zohra Haouas, Sameh Belgacem, Carmen Peralta, Hassen Ben Abdennebi
Summary: This study found that diclofenac has beneficial effects on hepatic ischemia/reperfusion injury (IRI) by reducing oxidative stress, inflammation, and apoptosis. It activates the eNOS pathway, which contributes to its protective effects.
Article
Green & Sustainable Science & Technology
Thiago Lopes da Silva, Camila Stefanne Dias Costa, Meuris Gurgel Carlos da Silva, Melissa Gurgel Adeodato Vieira
Summary: This article provides detailed information about the properties of anti-inflammatory drugs found in water and effluents, the latest results on the concentration of these compounds in different aquatic environments, the main characteristics of AOP, and the recent achievements in oxidation processes aimed at degrading NSAIDs.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Chemistry, Multidisciplinary
Yun He, Hongjie Gao, Jiankang Liu
Summary: This study demonstrates an upgraded photoelectrochemical aptamer sensor for detecting diclofenac with high sensitivity and stability. By optimizing photoactive materials and bio-identification components, linear detection of DCF in low concentrations was achieved.
Article
Biochemistry & Molecular Biology
Alberto Galisteo, Fatin Jannus, Amalia Garcia-Garcia, Houssam Aheget, Sara Rojas, Jose A. Lupianez, Antonio Rodriguez-Dieguez, Fernando J. Reyes-Zurita, Jose F. Quilez del Moral
Summary: A variety of diclofenac N-derivatives were synthesized and tested for their anti-cancer and anti-inflammatory effects, showing significant inhibitory effects on cancer cell lines and inflammatory responses. These compounds have the potential to be effective therapeutic strategies against diseases such as cancer and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Mohammed M. Mehanna, Kawthar K. Abla, Souraya Domiati, Hoda Elmaradny
Summary: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain caused by inflammatory disorders, but their oral administration often leads to side effects. This study explored the delivery of NSAIDs via the skin as an attractive alternative. Different types of gels, including microemulsion-based hydrogel (MBH), were prepared and loaded with diclofenac. The physicochemical properties, permeation ability, irritation effect, and antinociceptive efficacy of the gels were evaluated. MBH showed the highest permeation ability, as well as the best results in terms of irritation and toxicity. It was concluded that limonene-containing microemulsion hydrogel is a promising lipid-based vehicle for safe and effective pain treatment.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Review
Genetics & Heredity
Hoang Kim Tu Trinh, Le Duy Pham, Kieu Minh Le, Hae-Sim Park
Summary: Non-steroidal anti-inflammatory drugs (NSAIDs) are the main cause of drug hypersensitivity reactions worldwide, with diverse clinical phenotypes that can be classified into cross-reactive or selective responses. Genetic and epigenetic backgrounds play important roles in NSAID-induced hypersensitivity reactions.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Suryun Jung, Mingyu Kim, Suji Kim, Sooyeun Lee
Summary: Gamma-hydroxybutyric acid (GHB) is a potent central nervous system depressant derived from gamma-aminobutyric acid (GABA). GHB is used for medical purposes but has also been associated with date rape and club drug use. When combined with ethanol, GHB can increase sedation and cardiovascular dysfunction through additive effects on GABA receptors. Understanding the combined effects of GHB and ethanol is important for clinical and forensic interpretations of GHB intoxication.
Article
Environmental Sciences
Sorina Motoc, Florica Manea, Anamaria Baciu, Sergiu Vasilie, Aniela Pop
Summary: The development of simultaneous detection methods for anti-inflammatory drugs in water is challenging but important for water quality control. In this study, fullerene-carbon nanofiber (FULL/CNF) and graphene-carbon nanotubes (GR/CNT) were used for the first time as sensing elements for simultaneous determination of diclofenac, naproxen, and ibuprofen. The FULL/CNE electrode showed good performance with DPV-based detection, while the GR/CNT electrode achieved low limits of detection with MPA-based methodology. Both electrodes demonstrated good reproducibility, stability, and the ability to measure the drugs simultaneously in water samples.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Chemistry, Physical
Malgorzata Wasilewska, Anna Derylo-Marczewska
Summary: In this study, alginate-carbon composites with different active carbon content were synthesized and analyzed by various techniques. The obtained materials show potential as adsorbents for removing organic pollutants from water. The immobilization effect of activated carbon in calcium alginate was investigated, and the textural properties, morphology, and adsorption properties of the materials were studied.
Article
Environmental Sciences
Katarzyna Kolecka, Magdalena Gajewska, Magda Caban
Summary: The extent of pharmaceutical pollution in the environment requires more automatic and integrated solutions. This study focused on the correlation between sales data of non-steroidal anti-inflammatory drugs (NSAIDs) and their concentration in wastewater treatment plants (WWTPs). The findings suggest that a significant amount of sold NSAIDs are improperly disposed into the sewage system, emphasizing the need for future predictions and risk assessments to consider this factor.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Environmental Sciences
N. Hodkovicova, A. Hollerova, J. Blahova, P. Mikula, M. Crhanova, D. Karasova, A. Franc, S. Pavlokova, J. Mares, E. Postulkova, F. Tichy, P. Marsalek, J. Lanikova, M. Faldyna, Z. Svobodova
Summary: The study revealed the toxic effects of NSAIDs on the kidneys, liver, and gills of rainbow trout, with kidneys being the most affected organ, potentially leading to impaired oxygen transport. Furthermore, NSAIDs also impact the microbiota, causing gut dysbiosis.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Pharmacology & Pharmacy
Sepand Tehrani Fateh, Amir Salehi-Najafabadi
Summary: GHB and GBL are easily accessible recreational drugs that pose a high risk of adverse effects and mortality without specific antidotes. They can be found not only in clinical settings, beverages, and cosmetic products, but also have potential therapeutic options involving PPAR gamma and PON. It is important to classify GBL as a controlled substance.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Environmental Sciences
Xiangju Li, Xue Xue, Jia Jia, Xiaocui Zou, Yongjing Guan, Long Zhu, Zaizhao Wang
Summary: The overuse of antimicrobial agents is a key factor in the emergence of antibiotic resistance bacteria (ARB), but it is unclear whether non-antibiotic chemicals like nonsteroidal anti-inflammatory drug (NSAID) can induce ARB. This study investigated whether NSAID diclofenac (DCF) promotes the emergence of antibiotic resistance in Escherichia coli K12 MG1655. The results showed that DCF induced hereditary stable ARB and caused gene variation on the chromosome. DCF also triggered bacterial oxidative stress and SOS response, leading to enhanced expression of antioxidant and SOS system-related genes. However, high-dosage DCF reduced mutation frequency but enhanced mutant resistance.
ENVIRONMENTAL POLLUTION
(2023)
Article
Chemistry, Multidisciplinary
Syed Raza Shah, Zarbad Shah, Ajmal Khan, Ayaz Ahmed, Shariqa Khwaja, Rene Csuk, Muhammad U. Anwar, Ahmed Al-Harrasi
Summary: In this study, four new alkali metal complexes containing 1,10-phenanthroline and two non-steroidal anti-inflammatory drugs were synthesized and evaluated for their anticancer activity against lung and oral cancer cell lines. The complexes showed excellent activities against cancer cells with minimal toxicity towards normal cells.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Nattakanwadee Khumpirapang, Krit Suknuntha, Pathomwat Wongrattanakamon, Supat Jiranusornkul, Songyot Anuchapreeda, Petrine Wellendorph, Anette Mullertz, Thomas Rades, Siriporn Okonogi
Summary: The present study investigated the binding of Alpinia galanga oil (AGO) and its key compounds to GABA(A) receptors. It was found that only AGO and methyl eugenol displayed positive modulation at the highest concentrations. Computational modeling showed the stable structure of the GABA(A) receptor-methyl eugenol complex. An oil-in-water nanoemulsion containing AGO showed increased muscimol binding.
Article
Pharmacology & Pharmacy
Kantaporn Kheawfu, Surachai Pikulkaew, Petrine Wellendorph, Louise von Gersdorff Jorgensen, Thomas Rades, Anette Mullertz, Siriporn Okonogi
Summary: This study investigated the oil pathways and anesthetic mechanism of clove oil nanoformulations in fish. The results showed that nanoformulations increased penetration flux and achieved anesthesia by modulating GABA receptor binding.
Article
Chemistry, Organic
Keisuke Mitsui, Maria E. K. Lie, Naoki Saito, Koichi Fujiwara, Mizuki Watanabe, Petrine Wellendorph, Satoshi Shuto
Summary: Novel gamma-aminobutyric acid (GABA) analogues with different backbones were designed based on the analysis of the bioactive form of a previous inhibitor. These compounds were synthesized using ring-closing metathesis and compound 4 showed selective low micromolar potency.
Article
Pharmacology & Pharmacy
Line B. Palmelund, Geeske M. van Woerden, Hans Brauner-Osborne, Petrine Wellendorph
Summary: In this study, a cell-based ELISA assay was developed to quantitate pThr286 levels of CaMKII alpha. The assay showed high sensitivity and specificity, and was validated using known inhibitors and patient-related mutations. This assay provides a reproducible and easily implemented method for studying CaMKII alpha and evaluating potential drug candidates.
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2022)
Article
Medicine, Research & Experimental
Nane Griem-Krey, Stine J. Gauger, Emma K. Gowing, Louise Thiesen, Bente Frolund, Andrew N. Clarkson, Petrine Wellendorph
Summary: Ca2+/calmodulin-dependent protein kinase II alpha (CaMKII alpha) is a potential target for acute neuroprotection. A novel GHB analog, Ph-HTBA, was found to promote neuroprotection after stroke, potentially through reducing CaMKII alpha phosphorylation. Ph-HTBA may have distinct molecular interactions with the hub cavity, contributing to its superior neuroprotective effect compared to other GHB analogs.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Lisa Pallareti, Tine F. Rath, Boris Trapkov, Tsonko Tsonkov, Anders Thorup Nielsen, Kasper Harpsoe, Patrick R. Gentry, Hans Brauner-Osborne, David E. Gloriam, Simon R. Foster
Summary: This study used virtual screening, analog searches, and pharmacological assays to investigate GPR139 signaling and identify improved compounds. The rank order of potency of reference agonists was consistent across assays, and several new agonists and antagonists were identified. These findings contribute to the GPR139 tool compound repertoire.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yufang Deng, Claudia V. Perez Almeria, Lieke van Gijzel, Kay Schaller, Line Vedel, David E. Gloriam, Trond Ulven, Hans Brauner-Osborne
Summary: This study systematically investigated the structure-activity relationship of GPR15L(71-81) using truncations/extensions, alanine-scanning, and N- and C-terminal capping. The results showed that the C-terminal alpha carboxyl group and the residues Leu(78), Pro(75), Val(74), and Trp(72) are critical for receptor interaction and contribute significantly to the peptide potency. Additionally, the study also identified the importance of Lys192 and Glu272 residues in GPR15 for the potency of the GPR15L peptide.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jens V. Andersen, Arne Schousboe, Petrine Wellendorph
Summary: Synaptic regulation of GABA, the primary inhibitory neurotransmitter, is crucial for brain function. Astrocytes play fundamental roles in regulating synaptic GABA signaling by removing excess GABA from the synapse and using it as a metabolic substrate for glutamine synthesis. The flow of GABA and glutamine between neurons and astrocytes, known as the GABA-glutamine cycle, is essential for maintaining inhibitory signaling.
ESSAYS IN BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yufang Deng, Ee Von Moo, Asuka Inoue, Hans Braeuner-Osborne
Summary: GPR15 is involved in immune disorders and its internalization mechanism was studied. The study found that GPR15 internalization is moderately dependent on GRKs and clathrin, and highly dependent on caveolin and dynamin. Additionally, a bystander arrestin recruitment assay showed that GPR15 recruits arrestin-3 to the cell membrane upon agonist stimulation. Overall, this study provides new insights into beta-arrestin recruitment and receptor internalization mechanisms for GPR15.
Article
Endocrinology & Metabolism
Nane Griem-Krey, Anders B. Klein, Bettina H. Clausen, Mathias R. J. Namini, Pernille Nielsen, Mozammel Bhuiyan, Raghavendra Y. Nagaraja, T. Michael De Silva, Christopher G. Sobey, Heung-Chin Cheng, Cyrille Orset, Denis Vivien, Kate L. Lambertsen, Andrew N. Clarkson, Petrine Wellendorph
Summary: The cyclic GHB analogue 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) improves sensorimotor function and hippocampal neuronal activity after stroke in mice when administered with alteplase at a clinically relevant time. It regulates CaMKII signaling and alleviates aberrant CaMKII signaling after cerebral ischemia without affecting physiological CaMKII signaling.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Biochemical Research Methods
S. Sadia Ameen, Nane Griem-Krey, Antoine Dufour, M. Iqbal Hossain, Ashfaqul Hoque, Sharelle Sturgeon, Harshal Nandurkar, Dominik F. Draxler, Robert L. Medcalf, Mohd Aizuddin Kamaruddin, Isabelle S. Lucet, Michael G. Leeming, Dazhi Liu, Amardeep Dhillon, Jet Phey Lim, Faiza Basheer, Hong-Jian Zhu, Laita Bokhari, Carli L. Roulston, Prasad N. Paradkar, Oded Kleifeld, Andrew N. Clarkson, Petrine Wellendorph, Giuseppe D. Ciccotosto, Nicholas A. Williamson, Ching-Seng Ang, Heung-Chin Cheng
Summary: Excitotoxicity is a neuronal death process initiated by over-stimulation of glutamate receptors. Proteolytic processing of proteins, particularly by calpains, plays a critical role in this process. Our study identified key synaptic regulatory proteins as substrates of calpains, and their proteolysis contributes to neuronal death by disrupting synaptic organization and function. Blocking calpain-mediated proteolysis of Src protein showed neuroprotective effects. Our findings provide new insights into excitotoxic neuronal death mechanisms and potential targets for neuroprotection.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Clinical Neurology
Louise Piilgaard, Laura Rose, Jessica L. Justinussen, Camille Gylling Hviid, Rene Lemcke, Petrine Wellendorph, Birgitte Rahbek Kornum
Summary: This study evaluated the digital ventilated home-cage (DVC®) activity system as an alternative for detecting Narcolepsy type 1 (NT1) features in NT1 mouse models. The results showed that NT1 mice exhibited altered dark phase activity and increased state transitions compared to wild-type mice, and the inability to sustain activity periods >40 min was identified as a robust NT1 biomarker. Additionally, a nest-identification algorithm was developed to differentiate between inactivity and activity, which showed significant correlations with sleep/wake behavior assessed by EEG/EMG.
Article
Chemistry, Medicinal
F. Bavo, S. Kickinger, M. E. K. Lie, C. Avgerinos, K. S. Wilhelmsen, P. Wellendorph, B. Frolund
Summary: In this study, a series of conformationally constrained isoserine analogs with defined stereochemistry were designed and synthesized. Two of these analogs, (2S,2 ' S)-6 and (2S,2 ' S)-7, showed the strongest inhibition activity against GAT3, comparable to (S)-isoserine, but with significantly improved selectivity. These novel ligands can serve as valuable tools to validate the proposed GAT3-mediated effect of (S)-isoserine.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Editorial Material
Biochemistry & Molecular Biology
Azadeh Shahsavar, Petrine Wellendorph
Summary: Two new structural studies of GAT1, a subtype of GABA transporter, provide detailed snapshots of the GABA transport cycle, offering insights into its mechanism and serving as blueprints for the design of novel drugs targeting GABAergic systems.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Meeting Abstract
Biophysics
Mette H. Poulsen, Feng Xue, Svetlana R. Maurya, Stefanie Kickinger, Samuel Usher, Petrine Wellendorph, Alicia Lundby, Stephan A. Pless
BIOPHYSICAL JOURNAL
(2023)