Search Results (38)

Pharmaceutically active compounds (PhACs), pesticides, and poly- and perfluoroalkyl substances (PFAS) are increasingly detected in surface waters at trace concentrations, raising concerns for both aquatic systems and, consequently, human health. Conventional solutions are insufficient to achieve complete removal at trace compound concentrations, highlighting the need for advanced separation technologies. This study aims to comprehensively analyze rejection and removal mechanisms of selected PhACs, pesticides, and PFAS present in water solutions at reported environmentally relevant concentrations (300 ng L⁻¹), using two nanofiltration (NF) and one reverse osmosis (RO) polyamide membrane. PhACs, pesticides, and PFAS were selected to cover a broad range of physicochemical properties, specifically molecular mass (MM), dissociation constant (pKa), and octanol–water partition coefficient (logK_o/w). Rejection values ranged from 42.1% (acetaminophen) to apparent 100% (for multiple compounds), depending on water pH, solute properties, and membrane characteristics. Size exclusion and electrostatic interactions were identified as the primary removal mechanisms, with hydrophobic interactions having a lower impact, particularly for carbamazepine, bezafibrate, and perfluorooctane sulfonic acid (PFOS). Addition of sodium chloride (3 g L⁻¹) decreased rejection of most negatively charged compounds due to suppression of membrane surface charge, although clarithromycin and ofloxacin exhibited improved rejection. Presented results provide fundamental insight into compound-specific membrane rejection and highlight the importance of membrane–solute interactions under environmentally realistic conditions. The results support further optimization of NF and RO for targeted compound rejection and provide a baseline for data-driven membrane process modeling. Full article

Fibrate pharmaceuticals (fibrates), as a widespread class of emerging contaminants, pose potential risks to both ecological systems and human health. The photocatalytic system based on nitrogen (N) and fluorine (F) co-doped TiO₂ nanotube arrays (NF-TNAs) provides a renewable solution for fibrate pharmaceutical removal from water, powered by inexhaustible sunlight. In this study, the degradation of two typical fibrates, i.e., bezafibrate (BZF) and ciprofibrate (CPF), under simulated sunlight irradiation through NF-TNAs were investigated. The photocatalytic degradation of BZF/CPF was achieved through combined radical and non-radical oxidation processes, while the generation and reaction mechanisms of associated reactive oxygen species (ROS) were examined. Electron paramagnetic resonance detection and quenching tests confirmed the existence of h⁺, •OH, O₂^•−, and ¹O₂, with O₂^•− playing the predominant role. The transformation products (TPs) of BZF/CPF were identified through high-resolution mass spectrometry analysis combined with quantum chemical calculations to elucidate the degradation pathways. The influence of co-existing ions and typical natural organic matters (NOM) on BZF/CPF degradation were also tested. Eventually, the ecological risk of BZF/CPF transformation products was assessed through quantitative structure–activity relationship (QSAR) modeling, and the results showed that the proposed photocatalytic system can largely alleviate fibrate toxicity. Full article

This study investigates the implications of sewage contamination in the coastal and riverine environments of Hout Bay, Cape Town, South Africa. Chemical analyses were applied to quantify the presence of pollutants such as pharmaceutical and personal care products (PPCPs) in sentinel marine organisms such as mussels, as well as microbial indicators of faecal contamination in river water and seawater, for estimating the extent of impact zones in the coastal environment of Hout Bay. This research investigated the persistent pharmaceuticals found in marine outfall wastewater effluent samples in Hout Bay, examining whether these substances were also detectable in marine biota, specifically focusing on Mytilus galloprovincialis mussels. The findings reveal significant levels of sewage-related pollutants in the sampled environments, with concentrations ranging from 32.74 to 43.02 ng/g dry weight (dw) for acetaminophen, up to 384.96 ng/g for bezafibrate, and as high as 338.56 ng/g for triclosan. These results highlight persistent PPCP contamination in marine organisms, with increasing concentrations observed over time, suggesting a rise in population and pharmaceutical use. Additionally, microbial analysis revealed high levels of E. coli in the Hout Bay River, particularly near stormwater from the Imizamo Yethu settlement, with counts exceeding 8.3 million cfu/100 mL. These findings underscore the significant impact of untreated sewage on the environment. This study concludes that current sewage treatment is insufficient to mitigate pollution, urging the implementation of more effective wastewater management practices and long-term monitoring of pharmaceutical levels in marine biota to protect both the environment and public health. Full article

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments. This systematic review and meta-analysis evaluate the efficacy and safety of novel oral anti-cholestatic agents for PBC. Methods: A systematic literature search was conducted in electronic databases up to September 2024. Randomized controlled trials, cohort studies, and case-control studies evaluating novel oral anti-cholestatic agents in adult PBC patients were included. The primary outcome was a change in alkaline phosphatase (ALP) levels. Safety was assessed by the incidence of serious adverse events. Random-effect meta-analyses were performed. Results: Ten studies involving 878 patients were analyzed. Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. The meta-analysis showed significant reductions in ALP levels with novel agents compared to the controls (SMD −2.80; 95% CI −3.56, −2.03; p < 0.00001), with high heterogeneity (I² = 93%). Saroglitazar achieved the largest effect size. There was no significant difference in serious adverse events between novel agents and controls (OR 1.21; 95% CI 0.81, 1.83; p = 0.35). Conclusions: Novel oral anti-cholestatic agents show promise in improving biochemical markers in PBC patients with suboptimal UDCA responses, with a safety profile comparable to controls. However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety. Full article

Background/Objectives: Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic disease of the liver that symptomatically can present with pruritus and fatigue. Its established first- and second-line therapies are ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) although they provide limited symptom management. Liver transplantation offers a potentially curative therapeutic option in refractory cases progressing to cirrhosis. Novel research published after the current guidelines highlights the importance of providing an up-to-date analysis of treatment options available. Methods: In this study, we conducted a literature search using Pubmed, Ovid Medline, and SCOPUS to provide a narrative review of first-line, second-line, and emerging therapies in PBC. Results: UDCA has been well established as a long-term, safe therapy within the literature although it is possible that treatment dosage can be further optimised in refractory patients. It has a favourable side effect profile. Despite improving biochemical markers, histopathological profile, and overall outcomes, up to 30–40% of patients are refractory to it. Age and sex are highlighted as independent indicators of non-responsiveness. This necessitates effective second-line therapies. Future trials could aim to investigate UDCA as a co-first-line therapy. Further supporting results for OCA were found in the interim extension trial of the seminal POISE study. The long-term phase 4 COBOLT trial is still awaiting results to further assess the complications, adherence, and potential adverse effects. It is a viable option in UDCA-refractory patients. The high incidence rate of dose-related pruritis indicates that alternative second-line options are needed. Bezafibrate is an off-label antilipemic agent that shows promise as a prospective second-line therapy option. The landmark BEZURSO trial alleviated some efficacy and safety concerns, but it remains associated with elevated serum creatinine; thus, it should be considered with caution. Other prospective second-line therapies are budesonide, triple therapy, and novel agents such as seladelpar and elafibranor. Conclusions: UDCA should remain the treatment of choice for PBC, though perhaps not as monotherapy. With further investigation, BF shows promise as a new second-line therapy alongside OCA, which it may outperform. Full article

This study investigates the effectiveness of blast furnace slags (BFSs) as catalysts in the ozonation process to degrade complex contaminants such as bezafibrate (BFZ) at different pH levels. The findings reveal that the presence of BFS enhances degradation efficiency, achieving a 10% improvement at pH 10 and a 30% improvement at pH 5.5 compared to simple ozonation. The highest degradation efficiency was observed in the Ozonation–BFS system at pH 10, with 90% decomposition of BFZ. These results were corroborated through ozone consumption analysis, BOD5 measurements, and the identification of oxalic acid as the final decomposition product. Due to the complexity of the reaction system, kinetic characterization was performed using non-parametric modeling based on differential neural networks. The model indicated that the observed reaction rate for BFZ degradation in the presence of ozone and BFS was 4.12 times higher at pH 5.0 and 1.08 times higher at pH 10.0 compared to simple ozonation. These results underscore the potential of using BFS in catalytic ozonation processes for the effective treatment of recalcitrant contaminants in wastewater. Full article

Three peroxisome proliferator-activated receptor subtypes, PPARα, PPAR(ß/)δ, and PPARγ, exert ligand-dependent transcriptional control in concert with retinoid X receptors (RXRs) on various gene sets harboring PPAR response elements (PPREs) in their promoter regions. Ligand-bound PPAR/RXR complexes do not directly regulate transcription; instead, they recruit multiprotein coactivator complexes to specific genomic regulatory loci to cooperatively activate gene transcription. Several coactivators are expressed in a single cell; however, a ligand-bound PPAR can be associated with only one coactivator through a consensus LXXLL motif. Therefore, altered gene transcription induced by PPAR subtypes/agonists may be attributed to the recruitment of various coactivator species. Using a time-resolved fluorescence resonance energy transfer assay, we analyzed the recruitment of four coactivator peptides (PGC1α, CBP, SRC1, and TRAP220) to human PPARα/δ/γ-ligand-binding domains (LBDs) using eight PPAR dual/pan agonists (bezafibrate, fenofibric acid, pemafibrate, pioglitazone, elafibranor, lanifibranor, saroglitazar, and seladelpar) that are/were anticipated to treat nonalcoholic fatty liver disease. These agonists all recruited four coactivators to PPARα/γ-LBD with varying potencies and efficacy. Only five agonists (bezafibrate, pemafibrate, elafibranor, lanifibranor, and seladelpar) recruited all four coactivators to PPARδ-LBD, and their concentration-dependent responses differed from those of PPARα/γ-LBD. These results indicate that altered gene expression through consensus PPREs by different PPAR subtypes/agonists may be caused, in part, by different coactivators, which may be responsible for the unique pharmacological properties of these PPAR agonists. Full article

In this study, an electrochemical-assisted ferric ion/persulfate (EC/Fe³⁺/PS) process was proposed to degrade bezafibrate (BZF), a widespread hypolipidemic drug, in water. By promoting the reduction of Fe³⁺ to Fe²⁺ at the cathode, the introduction of an electric field successfully overcomes the limitation of non-regenerable Fe²⁺ inherent in Fe²⁺/PS systems, significantly improving the degradation efficiency of BZF. The predominant reactive species identified were •OH and SO₄^●−, with ¹O₂ also playing a role. Various key operational parameters were investigated and optimized, including the current intensity, Fe³⁺ dosage, PS concentration, and initial pH. With a current intensity of 50 mA, an Fe³⁺ concentration of 50 μΜ, a PS dosage of 50 μM, and an initial pH of 3, the degradation efficiency of BZF demonstrated an exceptional achievement, reaching up to 98.8% within 30 min. The influence of anions and humic acid was also assessed. An LC/TOF/MS analysis revealed four major degradation pathways of BZF: hydroxylation, amino bond cleavage, dechlorination, and fibrate chain removal. The acute and chronic toxicities of BZF and its degradation intermediates were then assessed using the ECOSAR program. These findings highlight the wide-ranging applications of the EC/Fe³⁺/PS system and its potential for remediating water contaminated with micropollutants. Full article

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT. Full article

This study is the first to report the high performance of calcined natural sphalerite as a heterogeneous catalyst (Catalyst) in the piezo- and photocatalytic degradation of pharmaceuticals (bezafibrate and ceftriaxone) using high-frequency ultrasound (US, 1.7 MHz) and ultraviolet-light-emitting diodes (LED, 365 nm). The kinetic comparison showed that piezo-photocatalysis (LED + US + Catalyst) was more efficient than photocatalysis (LED + Catalyst) for degrading both contaminants in deionized water as well as in surface river water at natural pH (7.9). Despite reducing degradation rates (~1.7 times) in river water due to the scavenging effect of its constituents, ceftriaxone and bezafibrate were degraded by 77% and 48% after 1 h of exposure, respectively. Adding H₂O₂ increased the corresponding pseudo-first-order rate constants, and the complete degradation of ceftriaxone was achieved. However, the contribution of ultrasound at a given intensity was hidden, which resulted in a similar performance of piezo-photocatalysis and photocatalysis for treating river water. No pronounced synergy between the piezo- and photocatalytic processes was observed in the experimental conditions used. Nevertheless, the H₂O₂-assisted piezo-photocatalysis using high-frequency US, LED, and natural catalysts can be considered a novel and effective strategy for eliminating pharmaceuticals from real water without pH adjustment. Full article

The number of patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is increasing globally and is raising serious concerns regarding the increasing medical and economic burden incurred for their treatment. The progression of NASH to more severe conditions such as cirrhosis and hepatocellular carcinoma requires liver transplantation to avoid death. Therefore, therapeutic intervention is required in the NASH stage, although no therapeutic drugs are currently available for this. Several anti-NASH candidate drugs have been developed that enable treatment via the modulation of distinct signaling cascades and include a series of drugs targeting peroxisome proliferator-activated receptor (PPAR) subtypes (PPARα/δ/γ) that are considered to be attractive because they can regulate both systemic lipid metabolism and inflammation. Multiple PPAR dual/pan agonists have been developed but only a few of them have been evaluated in clinical trials for NAFLD/NASH. Herein, we review the current clinical trial status and future prospects of PPAR-targeted drugs for treating NAFLD/NASH. In addition, we summarize our recent findings on the binding modes and the potencies/efficacies of several candidate PPAR dual/pan agonists to estimate their therapeutic potentials against NASH. Considering that the development of numerous PPAR dual/pan agonists has been abandoned because of their serious side effects, we also propose a repositioning of the already approved, safety-proven PPAR-targeted drugs against NAFLD/NASH. Full article

Sulfite predominantly accumulates in the brain of patients with isolated sulfite oxidase (ISOD) and molybdenum cofactor (MoCD) deficiencies. Patients present with severe neurological symptoms and basal ganglia alterations, the pathophysiology of which is not fully established. Therapies are ineffective. To elucidate the pathomechanisms of ISOD and MoCD, we investigated the effects of intrastriatal administration of sulfite on myelin structure, neuroinflammation, and oxidative stress in rat striatum. Sulfite administration decreased Fluoromyelin^TM and myelin basic protein staining, suggesting myelin abnormalities. Sulfite also increased the staining of NG2, a protein marker of oligodendrocyte progenitor cells. In line with this, sulfite also reduced the viability of MO3.13 cells, which express oligodendroglial markers. Furthermore, sulfite altered the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1), indicating neuroinflammation and redox homeostasis disturbances. Iba1 staining, another marker of neuroinflammation, was also increased by sulfite. These data suggest that myelin changes and neuroinflammation induced by sulfite contribute to the pathophysiology of ISOD and MoCD. Notably, post-treatment with bezafibrate (BEZ), a pan-PPAR agonist, mitigated alterations in myelin markers and Iba1 staining, and IL-1β, IL-6, iNOS and HO-1 expression in the striatum. MO3.13 cell viability decrease was further prevented. Moreover, pre-treatment with BEZ also attenuated some effects. These findings show the modulation of PPAR as a potential opportunity for therapeutic intervention in these disorders. Full article

Urban wastewaters contain pharmaceuticals that are not appropriately removed in conventional wastewater treatments, limiting treated water reuse. Microalgae have been shown to remove pharmaceuticals from urban wastewater in laboratory trials, but few studies have been conducted under natural conditions. In this work, pharmaceutical removal was assessed in a pilot-scale microalgal tertiary wastewater treatment in real conditions. Even after secondary treatment, the water contained measurable amounts of pharmaceuticals (an average of 218.4 ng/L) that significantly decreased to 39.83 ng/L at the exit of the microalgal system. Pharmaceuticals’ average removal rates were slightly higher in the summer (79.1%) than in autumn (71.1%). Antibiotics and antipsychotics were better removed (88.8 and 86.4%, respectively) than antihypertensives (75.3%) and others (Bezafibrate and Diclofenac; 64.0%). Physicochemical characteristics of the wastewater influenced pharmaceutical removal; significant positive correlations were observed between anti-hypertensive drug removal and ammonium concentration (r = 0.53; p < 0.05), total nitrogen and total pharmaceutical removal (r = 0.46; p < 0.05), and total nitrogen and antipsychotic drug removal (r = 0.47; p < 0.05). The results demonstrate the effectiveness of microalgal tertiary treatment in the removal of pharmaceuticals. Full article

Teas based on nutraceutical herbs are an effective tool against hyperlipidemia. However, the adulteration with chemical drugs is frequently detected. By coupling bioluminescent bioautography with high performance thin-layer chromatography (HPTLC), we developed a facile method suitable for screening hypolipidemic drugs (ciprofibrate and bezafibrate) adulteration in five different herbal teas (lotus leaf, Apocynum, Ginkgo biloba, Gynostemia and chrysanthemum). First, the sensitivity of a bioluminescent bacteria to the analyte was evaluated on different HPTLC layer materials, revealing that the best performance was achieved on the silica gel layer. On this basis, sample extracts were separated on silica gel plates via a standardized HPTLC procedure, forming a selective detection window for the targeted compound. Then, the separation results were rapidly visualized by the bioluminescence inhibition of bacteria cells within 6 min after dipping. The observed inhibition displayed an acceptable limit of detection (<20 ng/zone or 2 mg/kg) and linearity (R² ≥ 0.9279) within a wide concentration range (50–1000 ng/zone). Furthermore, the optimized method was performed with artificially adulterated samples and the recovery rates were determined to be within the range of 71% to 91%, bracing its practical reliability. Showing superiorly high simplicity, throughput and specificity, this work demonstrated that the analytical method jointly based on HPTLC and bioautography was an ideal tool for screening bioactive compounds in complex biological matrix. Full article

Wastewater discharge standards often play a crucial role in water environmental management. However, most of these standards only focus on conventional water pollutants such as chemical oxygen demand (COD), 5-day biochemical oxygen demand (BOD₅), ammonia (NH₃-N), total nitrogen (TN), and total phosphorus (TP). It is unclear if there is an impact on the removal of pharmaceuticals and personal care products (PPCPs). The Daqing River Basin is an important water system in China. In 2018, a new wastewater discharge standard for the Daqing River Basin (DB 13/2795–2018) was issued, which mainly limits the discharge of conventional water pollutants, including COD (20–40 mg L⁻¹), BOD₅ (4–10 mg L⁻¹), NH₃-N (1–2 mg L⁻¹), TN (10–15 mg L⁻¹), and TP (0.2–0.4 mg L⁻¹). Herein, we evaluated the performance of the new wastewater discharge standard, especially the effect on the removal of PPCPs. We characterized the occurrence of PPCPs and the resulting ecological impact in the basin, and compared the occurrence of PPCPs before (2017) and after (2021) implementation of the standard. A total of 16 PPCPs were detected, of which diclofenac, carbamazepine, ibuprofen, and bezafibrate pose risks to crustaceans and fish in the basin. A positive impact from the implemented standard, on the removal of some PPCPs, was confirmed, especially for lincomycin and trimethoprim. Full article