Hypertension (HTN) is a major global health burden and a leading risk factor for cardiovascular morbidity and mortality. Although numerous studies have explored host genetic factors and molecular mechanisms underlying HTN, increasing evidence indicates that gut microbiota dysbiosis also contributes to disease development. However, the specific microbial genes involved in HTN pathogenesis and their potential therapeutic targeting remain largely unexplored. This study aimed to identify HTN-associated differentially abundant bacterial genes (DAGs), prioritize bacterial key genes (bKGs) from among them, and repurpose potential therapeutic agents targeting these bKGs using an integrated bioinformatics framework. A total of 167 stool (fecal) microbiome samples, comprising 72 samples from HTN patients and 95 samples from HCs, were analyzed using publicly available 16 S rRNA sequencing data. After quality processing and clustering at 97% similarity, 95,361 representative operational taxonomic units were obtained. Microbial diversity analysis revealed significant alterations in community composition between HTN and HC groups. Differential abundance analysis identified 24 significantly altered bacterial genera associated with HTN. Functional prediction analysis further revealed 28 differentially abundant metabolic pathways and 631 differentially abundant bacterial genes (DAGs) potentially involved in HTN pathogenesis. From these DAGs, protein-protein interaction network analysis prioritized ten hub genes as bKGs (alsB, ampC, gsiB, araC, coaA, dnaB, fruA, ssuA, minE and tsx) representing potential microbial therapeutic targets. Structure-based molecular docking identified five approved drugs, namely Azilsartan, Eplerenone, Candesartan, Conivaptan, and Telmisartan, as top-ranked compounds exhibiting strong binding affinities toward the proposed targets. ADMET evaluation suggested favorable pharmacokinetic and safety profiles for Azilsartan, Eplerenone, and Candesartan. Furthermore, molecular dynamics simulation analyses confirmed that Eplerenone and Candesartan exhibited greater structural stability and sustained binding interactions, suggesting their potential as promising therapeutic candidates for HTN management. Therefore, this study identifies microbial gene signatures potentially involved in HTN and proposes a microbiome-guided drug repurposing strategy targeting bacterial functional pathways. These findings provide novel insights into microbiota-host interactions in HTN and highlight promising therapeutic candidates that warrant further experimental and clinical validation.

This study evaluated the chemical and microbiological stability of six oral liquid formulations, benazepril hydrochloride, candesartan cilexetil, disulfiram, fluconazole, methocarbamol, and pentoxifylline, compounded in the suspending vehicle SyrSpend® SF PH4. Stability-indicating UHPLC methods were validated for each API and confirmed to be specific, precise, accurate, and linear within the analytical ranges tested. Forced degradation studies ensured method suitability for detecting potential decomposition pathways. Chemical stability was assessed over 90 days under room temperature and refrigerated storage, alongside pH monitoring and visual inspection. Antimicrobial effectiveness testing (USP <51>, Category 3: oral aqueous products) demonstrated that all formulations met preservative efficacy criteria at the final assigned BUD. Results revealed API-specific stability profiles: several formulations remained within 90-110% of label claim for up to 90 days, while others showed temperature degradation patterns dictating shorter BUDs. Overall, SyrSpend® SF PH4 proved to be a versatile and reliable vehicle for compounded oral liquids, supporting extended BUDs while maintaining physicochemical integrity and microbiological quality. These findings reveal dependent degradation patterns that dictate shorter BUDs. Overall, SyrSpend® SF PH4 proved to be a versatile and reliable vehicle for compounded oral liquids, supporting extended BUDs while preserving physicochemical integrity and microbiological quality. These findings provide evidence-based guidance for compounding pharmacists and reinforce the role of SyrSpend® SF PH4 in personalized pharmacotherapy.

The presence of organic micropollutants in highly modified lowland rivers is a growing concern for the environment and human health. This study employs both target and non-target analysis over two years with high spatiotemporal resolution in the Münstersche Aa River which is influenced by both agricultural and urban land use to identify major stressors, their input pathways and the impact of low-flow conditions. Treated wastewater is the major input pathway for pharmaceuticals, illicit drugs as well as for pesticides and biocides. Moreover, urban and agricultural non-point sources contribute to the input of organic micropollutants. Database search identified sartans as a therapeutic class of pharmaceuticals of interest in the river and spatiotemporal analysis for two years showed wastewater treatment plants as the major input source with highest concentrations of >1 μg/L in summer at low-flow conditions for the sartans. Thereby, mean concentrations of candesartan and valsartanic acid as well as the carbamazepine metabolite 10,11-dihydro-10,11-dihydroxycarbamazepine exceeded health orientation values. For the first time, the UV protection agent 2-[4-(Diethylamino)-2-hydroxybenzoyl] benzoic acid (DHHB) was tentatively identified in a river. Fold change analysis at Lake Aasee, which is a small, shallow reservoir lake in the Münstersche Aa River system, stagnant at low and flowing at high discharge, revealed that elimination and associated formation processes are responsible for the changing occurrence of features at the inflow and outflow of the lake. The exact mechanisms need to be further evaluated. The present study provides valuable insights to stressors in high modified water bodies and shows that fold change analysis after non-target data processing is a valuable tool to gain insights into transformation processes in lakes and rivers which can aid in prioritizing research in the future.

This study presents a sustainable chemometric-assisted UV spectrophotometric strategy for the simultaneous determination of candesartan cilexetil (CAN), chlorthalidone (CTL) and amlodipine (AML) in laboratory-prepared mixtures and commercial pharmaceutical formulations. Owing to the extensive spectral overlap of the three drugs in the UV region, conventional spectrophotometric methods are inadequate for their direct simultaneous analysis. To address this challenge, multivariate calibration models based on principal component regression (PCR), partial least squares (PLS) and genetic algorithm-optimized partial least squares (GA-PLS) were developed, enabling accurate quantification without prior separation or complex sample preparation. A design of experiments (DoE) approach was employed to construct the calibration set, while an independent validation set was generated using orthogonal array-based Latin hypercube sampling (OALHS) to ensure robust external validation across the concentration domain. The GA-PLS model enhanced predictive performance through effective wavelength selection, reducing spectral redundancy and improving model robustness. Furthermore, variable importance in projection (VIP) analysis was employed to identify the most influential spectral variables and provide insight into the spectral regions contributing to analyte quantification. The developed models exhibited excellent analytical performance, characterized by low calibration errors (root mean square error of calibration [RMSEC] < 0.30), strong predictive ability and satisfactory external validation results (RMSEP = 0.2278-0.4419; RRMSEP = 0.1558-0.3978), with recoveries ranging from 99.0% to 100.0%. The sustainability of the proposed methodology was assessed using the multi-colour assessment (MA) tool according to white analytical chemistry principles, yielding a high whiteness score and demonstrating superior environmental performance compared with conventional chromatographic methods. In addition, the graphical layout tool for analytical chemistry evaluation (GLANCE) visualization framework provided a comprehensive graphical assessment of analytical performance and sustainability metrics. The proposed chemometric strategy offers a rapid, reliable, cost-effective and environmentally friendly alternative for routine quality control of multicomponent pharmaceutical formulations.

Granular activated carbon (GAC) filtration is increasingly used for quaternary treatment of municipal wastewater to remove organic micropollutants, in line with the revised EU Urban Wastewater Treatment Directive (Directive (EU) 2024/3019). This review compiles and synthesises available, peer-reviewed, and long-term pilot- and full-scale studies and, in contrast to previous reviews, particularly addresses breakthrough of Urban Wastewater Treatment Directive (UWWTD) relevant indicator compounds in relation to operational lifespan and regulatory compliance. Most studies were conducted at pilot scale, with considerable variation in empty bed contact time, filtration rate, and GAC type. Breakthrough of indicator compounds varied widely, but citalopram, metoprolol, benzotriazole, and methylbenzotriazole generally showed relatively late breakthrough, indicating potential for longer filter lifespan, whereas candesartan and irbesartan more often showed early breakthrough. The available data further indicate that the selection of indicator compounds strongly affects the operational lifespan over which compliance with the UWWTD may be maintained. However, the limited number of long-term full-scale studies and the large variability in pre-treatment, filter design, carbon type, and operating conditions prevent robust quantitative assessment of these relationships. The findings highlight the need for more large-scale, long-term studies using a systematic evaluation framework to support the effective implementation of GAC filtration for UWWTD compliance.

Traumatic brain injury (TBI), defined as a disruption in normal brain function caused by external mechanical force, affects ⁓27-69 million individuals annually worldwide. Despite its high prevalence and association with oxidative stress, neuroinflammation, and neurological deficits, no effective brain-targeted pharmacotherapy has yet been approved for TBI management. Herein, we report an intranasal (IN) candesartan-loaded mucoadhesive nanoemulsion (CND-MNE) designed to enhance nose-to-brain (N2B) delivery and therapeutic efficacy in TBI. The optimized CND-MNE exhibited a mean globule size of 20.98 ± 0.60 nm, spherical morphology, nasal-compatible pH, favourable spreading behaviour, enhanced flux and preserved mucosal integrity. CND-MNE revealed a 2.16- and 3.09-fold enhancement in brain Cmax compared with IN and intravenous suspensions (CND-SUS IN and CND-SUS IV), respectively. Additionally, enhanced N2B transport was confirmed by increased drug targeting efficiency (%DTE, 1.57-fold) and direct transport percentage (1.07-fold) compared to CND-SUS IN. In vivo, CND-MNE at high and low doses (HD, LD) reduced neurological severity scores (⁓4.8-fold and 4.0-fold), improved motor coordination [*P < 0.05 (HD)], spatial memory (****P < 0.0001, HD and LD), and recognition memory [*P < 0.05 (HD)] in the C57BL/6 controlled cortical impact model. Additionally, CND-MNE (HD and LD) markedly decreased brain water content (*P < 0.05) and preserved neuronal architecture. The levels of pro-inflammatory cytokines were lower in the CND-MNE-treated group than in the group treated with IN CND-SUS, indicating reduced neuroinflammation. Collectively, these findings highlight the potential of CND-MNE as an effective non-invasive strategy for targeted brain delivery and neuroprotection in TBI.

Preliminary evidence suggests that candesartan passes poorly into milk and is barely detectable in the plasma of breastfed infants. Use of candesartan is not a reason to discontinue nursing, but use caution in newborn and preterm infants.

The impact of China's national centralized volume-based procurement (NVBP) policy on antihypertensive drug procurement in underdeveloped, multi-ethnic regions remains understudied. This study evaluated changes in procurement prices, volumes, and costs for four antihypertensive drugs following the second NVBP batch in Guangxi, an economically disadvantaged region in southwestern China.

Candesartan (CDN) is a potent antagonist of the angiotensin II receptor known for its protective effects against cardiotoxicity. However, the oral administration of CDN exhibits limited therapeutic effectiveness due to factors such as first-pass hepatic metabolism, low solubility, and low bioavailability. This study's primary objective was to improve the cardioprotective efficacy of CDN in mitigating cardiotoxicity by developing a nasal in situ pH-sensitive formulation of CDN-loaded transbilosomes (ISPCLT). The Box-Behnken design was used to identify the optimal CDN-loaded transbilosome (CLT) formulation. The ISPCLT formulation was then developed by mixing the optimal CLT formulation with a mixture of chitosan and glyceryl monooleate. The bioavailability and efficacy of the ISPCLT formulation were examined in a cardiotoxicity rat model. The optimal CLT formulation consists of 262.6 mg of phospholipid, 20.4 mg of Span 60, and 10.2 mg of sodium deoxycholate. The ISPCLT formulation demonstrated a 2.55-fold increase in CDN release, a 7.04-fold increase in CDN permeation, and a 5.13-fold increase in CDN bioavailability compared to the free CDN suspension. The nasal ISPCLT formulation resulted in a 62.14% increase in body weight, a 95.98% decrease in lactate dehydrogenase levels, and a 93.39% reduction in CK-MB isoenzyme-MB levels when compared to the oral CDN suspension. Histopathological examination validated the ISPCLT formulation's cardioprotective action. The nasal ISPCLT formulation enhances patient adherence and minimizes the risk of adverse effects by allowing for lower dosages. The findings suggest that new strategies for managing cardiotoxicity may be viable with the nasal ISPCLT formulation.