Groundwater harbours unique species adapted to perpetual darkness. Groundwater fauna plays a crucial role in global ecosystem services, but contamination poses a threat to this keystone ecosystem. Diclofenac is a common non-steroidal anti-inflammatory drug of particular concern, due to its presence in both surface and groundwater. We assess the environmental risk of diclofenac in European groundwaters using different scenarios, analyzing Measured Environmental Concentrations (MECs) of diclofenac and estimating the Predicted No Effect Concentration (PNECs) through two approaches: considering the sensitivity of the groundwater crustacean Proasellus lusitanicus (Isopoda: Asellidae), and using surface water species as proxies. Our results show that scenarios based on surrogate species predict that groundwater ecosystems are at risk due to diclofenac contamination. On the other hand, the MECs of diclofenac were consistently lower than the PNEC of P. lusitanicus, suggesting that the current MECs do not pose a significant threat to this groundwater-adapted species. However, risk scenarios differ considering the sensitivity of other groundwater species, emphasizing the importance of considering multiple species\' sensitivities in risk assessment. Therefore, we recommend establishing an environmental quality standard for diclofenac in groundwater at 5 ng/L, a value that accounts the need for precautionary measures to safeguard groundwater ecosystems, essential for preserving their unique biota and services.

This work involved the preparation of pristine and iron nanoparticle-loaded biochar from a water chestnut shell to remove diclofenac sodium (DCF) containing effluent of pharmaceutical origin. To create suitable forecasting equations for the modelling of the DCF adsorption onto the adsorbent, response surface methodology (RSM) was used. The parameters, e.g. pH, adsorbent mass, DCF concentration and contact time, were used for the modeling of adsorption. The RSM model predicts that for 98.0% DCF removal, the ideal conditions are pH 6, an adsorbent dose of 0.5 g L-1, and a contact time of 60 min with an initial adsorbate concentration of 25 mg L-1 at 303 K. The maximum capacity deduced from the Langmuir model was 75.9 mg g-1 for pristine water chestnut shell biochar (pWCBC) and 122.3 mg g-1 for magnetically modified nano-Fe2O3 biochar (mWCBC). Under equilibrium conditions, the Langmuir model was the best-suited model compared to the Temkin and Freundlich models. The adsorption data in this investigation efficiently fitted the pseudo-second-order model, emphasizing that chemisorption or ion exchange processes may be involved in the process. The WCBC demonstrated recyclability after 10 cycles of repeated adsorption and desorption of DCF. A combined coagulation adsorption process removed COD, NH3-N, NO3-, PO43-, and DCF by 92.50%, 86.41%, 77.57%, 84.54%, and 97.25%, respectively. This study therefore shows that coagulation followed by adsorption onto biochar can be a cost-effective substitute for conventional pharmaceutical wastewater treatment.

UNASSIGNED: Non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac (DCF), form a significant group of environmental contaminants. When the toxic effects of DCF on plants are analyzed, authors often focus on photosynthesis, while mitochondrial respiration is usually overlooked. Therefore, an in vivo investigation of plant mitochondria functioning under DCF treatment is needed. In the present work, we decided to use the green alga Chlamydomonas reinhardtii as a model organism.
UNASSIGNED: Synchronous cultures of Chlamydomonas reinhardtii strain CC-1690 were treated with DCF at a concentration of 135.5 mg × L-1, corresponding to the toxicological value EC50/24. To assess the effects of short-term exposure to DCF on mitochondrial activity, oxygen consumption rate, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) production were analyzed. To inhibit cytochrome c oxidase or alternative oxidase activity, potassium cyanide (KCN) or salicylhydroxamic acid (SHAM) were used, respectively. Moreover, the cell\'s structure organization was analyzed using confocal microscopy and transmission electron microscopy.
UNASSIGNED: The results indicate that short-term exposure to DCF leads to an increase in oxygen consumption rate, accompanied by low MMP and reduced mtROS production by the cells in the treated populations as compared to control ones. These observations suggest an uncoupling of oxidative phosphorylation due to the disruption of mitochondrial membranes, which is consistent with the malformations in mitochondrial structures observed in electron micrographs, such as elongation, irregular forms, and degraded cristae, potentially indicating mitochondrial swelling or hyper-fission. The assumption about non-specific DCF action is further supported by comparing mitochondrial parameters in DCF-treated cells to the same parameters in cells treated with selective respiratory inhibitors: no similarities were found between the experimental variants.
UNASSIGNED: The results obtained in this work suggest that DCF strongly affects cells that experience mild metabolic or developmental disorders, not revealed under control conditions, while more vital cells are affected only slightly, as it was already indicated in literature. In the cells suffering from DCF treatment, the drug influence on mitochondria functioning in a non-specific way, destroying the structure of mitochondrial membranes. This primary effect probably led to the mitochondrial inner membrane permeability transition and the uncoupling of oxidative phosphorylation. It can be assumed that mitochondrial dysfunction is an important factor in DCF phytotoxicity. Because studies of the effects of NSAIDs on the functioning of plant mitochondria are relatively scarce, the present work is an important contribution to the elucidation of the mechanism of NSAID toxicity toward non-target plant organisms.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) carries a 3-15% risk of post-ERCP pancreatitis (PEP). Rectal indomethacin reduces the risk of PEP, but its cost has increased more than 20-fold over the past decade. Rectal diclofenac is also used to prevent PEP but is not commercially available in the United States. The aim of this study is to compare the incidence of PEP after administration of commercially available rectal indomethacin versus compounded rectal diclofenac and assess financial implications.
METHODS: ERCP cases at our institution with administration of 100 mg rectal indomethacin or 100 mg compounded rectal diclofenac between May 2018 and January 2022 were retrospectively reviewed. The incidence and severity of PEP was compared between the indomethacin (n = 728) and diclofenac (n = 304) groups. Risk factors (young age, female sex, history of pancreatitis or PEP, sphincterotomy during procedure, pancreatic indication, trainee involvement) and protective factors (prior sphincterotomy, pancreatic duct stenting) for PEP were compared between groups.
RESULTS: 60 patients (8.2%) in the rectal indomethacin group and 25 patients (8.2%) in the compounded rectal diclofenac group developed PEP, resulting in moderate or severe PEP in 9 (15.0%) and 2 (8.0%) patients, respectively. The compounded rectal diclofenac group had more trainee involvement (46.1% vs. 32.8%, p = 0.0001) and more prior sphincterotomy cases (15.8% vs. 10.6%, p = 0.0193) compared to the rectal indomethacin group; no statistically significant differences were observed in all other risk and protective factors. Following switch to compounded rectal diclofenac, institutional annual cost savings amounted to $441,460.62 and patient charge decreased 45-fold.
CONCLUSIONS: This retrospective single-center real-world analysis showed similar efficacy of rectal indomethacin and compounded rectal diclofenac in preventing PEP but demonstrates substantial cost savings after switching to compounded rectal diclofenac.

Diclofenac (DCF) is frequently detected in aquatic environments, emphasizing the critical need for its efficient removal globally. Here, we present the synthesis of Fe(III)-doped β-CD-grafted chitosan (Fe/β-CD@CS) cryogel beads designed for adsorbing DCF in aqueous solutions. The beads exhibited an average size of 2.94 ± 0.66 mm and a point of zero charge of 8.03. Adsorption experiments demonstrated that the Langmuir kinetic model provided the most accurate description of the kinetic data, while the Redlich-Peterson isotherm offered the best fit for the equilibrium data. The beads showcased a theoretical maximum adsorption capacity of 712.3 mg/g for DCF, with the adsorption process being identified as exothermic. DCF adsorption on the beads was attributed to hydrogen bonding, metal cation-π interactions, and electrostatic interactions. Reusability tests exhibited that the beads could be regenerated using 0.1 M NaOH. To perform deep learning modeling, adsorption experiments (n = 17), designed utilizing central composite design (CCD), were conducted in duplicate. The CCD framework incorporated input variables such as initial DCF concentration, adsorbent dosage, and solution pH, while the output variable was the DCF removal rate. Utilizing the adsorption data, an artificial neural network (ANN) model was constructed with a topology of 3: 7:10:1, featuring 3 input variables, 7 neurons in the first hidden layer, 10 neurons in the second layer, and 1 output variable. Employing the ANN model data, 3-D response surface plots were generated to elucidate the relationship between input variables and DCF removal rate. Additional adsorption tests were conducted to evaluate the developed ANN model, affirming its reliable predictability for the DCF removal rate. Analysis of the relative importance of the input variables revealed the following order of importance: solution pH (100 %) > adsorbent dosage (75.2 %) > initial DCF concentration (57.7 %).

UNASSIGNED: Rheumatoid arthritis (RA) is one of the most common forms of arthritis. Extracorporeal shockwave therapy (ESWT) has been identified as a viable alternative therapeutic approach in light of the present protracted clinical course of pharmacological treatment, and changes in levels of marker proteins in the blood samples of RA patients can be utilized to assess treatment outcomes.
UNASSIGNED: A randomized controlled trial was conducted involving forty patients diagnosed with rheumatoid arthritis (RA) who were assigned randomly to two groups. The first group received a combination of diclofenac and methotrexate (MTX) consisting of 25 mg of diclofenac administered thrice daily and 15 mg of MTX administered once weekly. Individual follow-up assessments were carried out after 7 and 14 days. Meanwhile, patients in the second group underwent two sessions of Extracorporeal Shockwave Therapy (ESWT), with a 7-day interval between sessions. Evaluations were conducted on day 7 and day 14. Patients who displayed pain control and stability were advised to continue the treatment, whereas those who had inflammation and discomfort were administered specific medications, and their progress was closely monitored until day 28. Blood samples were collected from both groups prior to treatment, after the first treatment, and after the second treatment. Four marker proteins (NRP-1, CELF-6, COX-2, and RGS-1) and two inflammatory cytokines (IL-6 and IL-17) were measured using western blot and RT-PCR techniques. A statistical analysis was conducted on the levels of specific proteins and inflammatory factors before and after treatment to evaluate its impact.
UNASSIGNED: Both groups exhibited statistically significant differences in the serum level of target biomarkers before and after the intervention. However, the ESWT group demonstrated a more noticeable effect, while the diclofenac + MTX group exhibited a delayed anti-inflammatory effect compared to ESWT.
UNASSIGNED: Both treatments significantly improved joint function, relieved pain, and reduced inflammation in patients. However, ESWT demonstrated a more prominent clinical analgesic effect compared to the combination treatment of diclofenac and MTX. Furthermore, ESWT produced a more immediate and noteworthy anti-inflammatory impact by regulating NRP-1 expression, a trophic factor receptor that facilitates vascular endothelial cell migration and tissue repair through angiogenesis, and regulating RGS-1 to limit inflammatory signal transmission and immune cell activation.

Diclofenac, often detected in environmental samples, poses a potential hazard to the aquatic environment. The present study aimed to understand the effect of this drug on photosynthetic apparatus, which is a little-known aspect of its phytotoxicity. Chloroplasts and thylakoids isolated from spinach (Spinacia oleracea) were used for this study and treated with various concentrations of diclofenac (from 125 to 4000 μM). The parameters of chlorophyll a fluorescence (the OJIP test) as measurements for both the intact chloroplasts and the thylakoid membranes revealed that isolated thylakoids showed greater sensitivity to the drug than chloroplasts. The relatively high concentration of diclofenac that is required to inhibit chloroplast and thylakoid functions suggests a narcotic effect of that drug on photosynthetic membranes, rather than a specific interaction with a particular element of the electron transport chain. Using confocal microscopy, we confirmed the degradation of the chloroplast structure after DCF treatment, which has not been previously reported in the literature. In conclusion, it can be assumed that diclofenac\'s action originated from a non-specific interaction with photosynthetic membranes, leading to the disruption in the function of the electron transport chain. This, in turn, decreases the efficiency of photosynthesis, transforming part of the PSII reaction centers into heat sinks and enhancing non-photochemical energy dissipation.

OBJECTIVE: Nitric oxide (NO) has various physiological activities. In this study, diclofenac (DF) which has a high affinity for human serum albumin (HSA) was nitrosylated to a novel NO donor (NDF). The cytotoxic effects and the mechanism of NDF were investigated.
METHODS: Binding experiments of NDF to HSA were performed by the ultrafiltration method. NO was measured by the Griess method. The number of dead cells were measured using annexin V. Apoptosis and endoplasmic reticulum stress were evaluated by western blotting.
RESULTS: NDF competitively inhibits the binding of DF to HSA, suggesting that NDF and DF have equivalent binding characteristics. NDF rapidly released NOx after being dissolved. At 200 μM, NDF induced cell death in human pancreatic cancer cells. Western blotting showed that NDF promoted the cleavage of PARP, caspase-3, and caspase-7. Inhibitors of caspase-1 and caspase-9 significantly suppressed NDF-induced cell death, as did a non-specific caspase inhibitor (Z-VAD). In addition, NDF significantly increased the expression of the endoplasmic reticulum stress marker, CHOP.
CONCLUSIONS: NDF induces apoptotic cell death by causing endoplasmic reticulum stress. The findings of this study suggest that NDF may become a promising compound for the treatment of pancreatic cancer.

OBJECTIVE: The aim of this study was to understand profiles of topical Voltaren gel diclofenac (VGD) 2.32 and 1.16% consumers through analyzing prescription patterns and to characterize treatment satisfaction, functional impairment, and pain relief after over-the-counter (OTC) VGD use in Sweden under real-world conditions.
METHODS: This observational, real-world study conducted in Sweden had retrospective and prospective segments. The retrospective secondary data segment utilized 12-month diclofenac gel prescription data from the Swedish eHealth Agency (E-hälsomyndigheten). The prospective segment included electronic surveys completed at baseline and weeks 4 and 12 by adult consumers who purchased OTC VGD to treat their pain.
RESULTS: Secondary data analyses (n = 12,145) showed that 56.7% of patients receiving diclofenac gel were females ≥70 years old. Most patients did not switch pain treatments; the mean time between diclofenac gel refills was about 2.5 months. From the surveys (n = 264), VGD provided pain relief, indicated by improvement in 11-point pain numeric rating scale scores. Average pain severity at baseline was 5.8 - improving by a mean of 1.3 and 1.9 points at weeks 4 and 12, respectively. The majority of consumers reported improvement in daily functioning (i.e., health-related quality of life [HRQoL]), and most were at least somewhat satisfied with VGD treatment results.
CONCLUSIONS: This real-world study provides important insights into the prescription patterns of diclofenac gel and the consumer experience with OTC VGD in Sweden. Patients rarely switched to other topical nonsteroidal anti-inflammatory drugs, and VGD consumers reported pain relief and improved HRQoL compared to baseline - resulting in treatment satisfaction.

Herein, we report the efficient photocatalytic degradation of the diclofenac drug using the Zn1-x-yPrxAlyO photocatalyst [x, y] = (0.00, 0.00), (0.03, 0.01), (0.03,0.03) under UV light irradiation. The analysis of the structure reveals that the Pr3+ and Al3+ cations insertion into the ZnO lattice leads to a decrease in the lattice constant (a and c), Zn-O bond length, strain lattice, and crystallite size. These alterations are linked to the high degree of atomic disorder triggered by the dopants, which produce stress and strain in the ZnO structure. The Raman measurements confirmed the structural phase and showed changes in the position and intensity of the E2High mode, associated with oxygen vibrations and material crystallinity. The presence of the dopants reduces the concentration of VZn and VO++ type defects while increasing the levels of VO, VO+, and Oi defects, as observed from the fitting of the Photoluminescence spectra. Furthermore, it was noted that de Pr3+ and Al3+ cations insertion into ZnO increases the optical band gap, which is associated with the Moss-Burstein effect. The micrograph images show that dopants transform the morphology from quasi-spherical particles to irregular cluster structures. The textural analysis indicated that an increase in the concentration of Al3+ in the ZnO lattice led to a higher surface area, likely enhancing photocatalytic activity. The sample containing 3% Pr3+ and 3% Al3+ showed the highest photocatalytic activity and degraded up to 71.42% of diclofenac. In addition, experiments with scavengers revealed that hydroxyl radicals are the main species involved in the drug\'s photodegradation mechanism. Finally, the Zn1-x-yPrxAlyO compound is highly recyclable and stable.