Pharmaceuticals最新文献

{"title":"The Impact of Comorbidities on the Discontinuation of Antifibrotic Therapy in Patients with Idiopathic Pulmonary Fibrosis.","authors":"Stefano Kette, Nicolò Reccardini, Francesco Salton, Paola Confalonieri, Alessia Andrisano, Maria Chianese, Anna De Nes, Marta Maggisano, Alessandra Galantino, Salvatore Nicolosi, Marco Mari, Andrea Salotti, Darina Angoni, Maria Chernovsky, Michael Hughes, Marco Confalonieri, Lucrezia Mondini, Barbara Ruaro","doi":"10.3390/ph18030411","DOIUrl":"10.3390/ph18030411","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown aetiology. Evidence on the progression of idiopathic pulmonary fibrosis (IPF) following the introduction of antifibrotic therapies still indicates a generally poor prognosis. IPF is associated with both respiratory and non-respiratory comorbidities, which can worsen symptoms and impact overall survival. <b>Background/Objectives</b>: The study aimed to investigate the effect of these comorbidities on the early and permanent discontinuation of pirfenidone or nintedanib in IPF patients. <b>Methods</b>: In this single-centre retrospective study, 101 patients diagnosed with IPF according to ATS/ERS/JRS/ALAT guidelines were treated with AFT. Clinical data were collected at 12 months prior to and up to 24 months following treatment initiation, including age, gender, smoking history, and the presence of respiratory and non-respiratory comorbidities. <b>Results:</b> The data showed that 21 patients (20.8%) discontinued treatment within the first 12 months. Additionally, pre-treatment comorbidities were not statistically correlated with the suspension of antifibrotic treatment. Among the overall cohort, 77 patients (76.2%) had at least one comorbidity and 27 (26.7%) had three or more comorbidities. Notably, 24 (23.8%) had respiratory comorbidities, while 75 (74.3%) had non-respiratory comorbidities. <b>Conclusions:</b> This real-life study emphasises the complexities involved in managing IPF, particularly regarding adherence to treatment when significant comorbidities are present. The evidence suggests that in patients with IPF, pre-treatment respiratory or non-respiratory conditions do not affect AFT discontinuation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Insights into the Antioxidant Activity of Luteolin: Density Functional Theory Analysis and Docking in Cytochrome P450 17A1.","authors":"Antônio Sérgio Nakao de Aguiar, Lucas Barbosa Ribeiro de Carvalho, Clayson Moura Gomes, Murillo Moraes Castro, Frederico Severino Martins, Leonardo Luiz Borges","doi":"10.3390/ph18030410","DOIUrl":"10.3390/ph18030410","url":null,"abstract":"<p><p><b>Background:</b> Luteolin, a flavonoid with well-documented antioxidant properties, has garnered significant attention for its potential therapeutic effects. <b>Objectives</b>: This study aims to investigate the antioxidant properties of luteolin under the influence of solvents, utilizing computational techniques to elucidate its interactions and its potential role as a modulator of enzymatic activities, particularly with Cytochrome 17A1. <b>Methods</b>: Density Functional Theory (DFT) calculations were employed to determine luteolin's electronic and structural characteristics. Key aspects analyzed included electron density distribution and the energies of the frontier molecular orbitals (HOMO and LUMO). Free radical scavenging mechanisms were explored by comparing the dissociation enthalpy of the O-H bond in the absence and presence of water molecules. Additionally, molecular docking simulations were performed to assess the interactions of luteolin with Cytochrome 17A1, identifying preferred binding sites and interaction energies. <b>Results</b>: The findings indicate that luteolin possesses distinct structural and electronic features that contribute to its effectiveness in protecting against oxidative stress. However, hydrogen bonding interactions with water molecules were found to influence the dissociation enthalpy of the O-H bond. Docking simulations revealed significant interaction profiles between luteolin and Cytochrome 17A1, suggesting its potential role as a modulator of this protein. <b>Conclusions</b>: This study underscores the therapeutic potential of luteolin and highlights the importance of computational techniques in predicting and understanding the molecular interactions of bioactive compounds with biological targets. The results provide valuable insights that may aid in developing new therapeutic strategies for diseases associated with oxidative stress.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatographic Analysis and Enzyme Inhibition Potential of <i>Reynoutria japonica</i> Houtt.: Computational Docking, ADME, Pharmacokinetic, and Toxicokinetic Analyses of the Major Compounds.","authors":"Tugsen Buyukyildirim, Fatma Sezer Senol Deniz, Osman Tugay, Ramin Ekhteiari Salmas, Onur Kenan Ulutas, Ibrahim Ayhan Aysal, Ilkay Erdogan Orhan","doi":"10.3390/ph18030408","DOIUrl":"10.3390/ph18030408","url":null,"abstract":"<p><p><b>Background:</b><i>Reynoutria japonica</i> Houtt. has been used for inflammatory diseases, skin burns, and high cholesterol in traditional Chinese medicine, and the roots and rhizomes of the plant were registered in the Chinese Pharmacopoeia. This study evaluated the enzyme inhibitory activities of <i>R. japonica</i> extracts from Türkiye. Its major phytochemical content was elucidated, molecular interaction studies of the main compounds were conducted, and toxicokinetic predictions and absorption, distribution, metabolism, and elimination studies were performed with in silico methods. <b>Methods</b>: <i>R. japonica</i> extracts were tested for their enzyme inhibitory activities using an ELISA microplate reader. The phytochemical profile was elucidated by LC-MS QTOF. Docking and other in silico studies evaluated interactions of its main components with cholinesterase, collagenase, and elastase. <b>Results</b>: <i>R. japonica</i> exhibited significant cholinesterase inhibitory effectiveness, while the stem and root extracts showed moderate tyrosinase inhibition. <i>R. japonica</i> leaf (IC₅₀ = 117.20 ± 4.84 g/mL) and flower extracts (IC₅₀ = 111.40 ± 1.45 µg/mL) exhibited considerable elastase activity. <i>R. japonica</i> leaf (IC₅₀ = 171.00 ± 6.76 g/mL) and root (IC₅₀ = 160.00 ± 6.81 g/mL) extracts displayed similar and potent collagenase inhibition. In the LC-MS QTOF analysis, procyanidin dimer, catechin, piceid, torachrysone, and its glucoside isomers were identified as the major components and resveratrol as the minor component. Galloylglucose showed the strongest binding at cholinesterase <i>via</i> key hydrogen bonds, while emodin-6-glucoside and emodin formed stable interactions with elastase. Piceid displayed significant polar and water-mediated contacts with collagenase. These findings underscore the potential of these ligands as protein inhibitors. In silico predictions reveal that emodin possessed the most favorable drug-like properties but posed potential interaction risks. <b>Conclusions</b>: This research represents the first investigation of the bioactivity and phytochemistry of <i>R. japonica</i> grown and documented in 2020 in Türkiye. Our findings point out that <i>R. japonica</i> could be used for cosmetic purposes, and further studies on neurological disorders could be performed.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Evaluation of Esters of Quinoxaline-1,4-di-<i>N-</i>oxide Derivatives as New Antitaeniasis Agents and Their Inhibitory Activity Against Triosephosphate Isomerase.","authors":"Francisca Palomares-Alonso, Alonzo González-González, Alma D Paz-González, Eyra Ortiz-Pérez, Ana Verónica Martínez-Vázquez, Itzhel García-Torres, Gabriel López-Velázquez, Helgi Jung-Cook, Gildardo Rivera","doi":"10.3390/ph18030406","DOIUrl":"10.3390/ph18030406","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Pork tapeworm <i>Taenia solium</i> is the causative agent of cysticercosis which may develop in muscle tissue, skin, eyes, and the central nervous system (neurocysticercosis). It is estimated by the World Health Organization (WHO) that about 2.56-8.30 million are infected worldwide. Praziquantel and albendazole are used for anthelminthic treatment of neurocysticercosis; however, not all patients have a complete elimination of cysts, which makes it necessary to seek new and improved treatment options. <b>Methods:</b> In this study, methyl, ethyl, n-propyl, and iso-propyl quinoxaline-7-carboxylate-1,4-di-<i>N</i>-oxide derivatives were evaluated in vitro against <i>Taenia crassiceps (T. crassiceps)</i> cysts. Additionally, to know their potential mode of action, a molecular docking analysis on <i>T. solium</i> triosephosphate isomerase (<i>Ts</i>TIM) and an enzyme inactivation assay on recombinant <i>Ts</i>TIM were carried out. <b>Results:</b> Nine compounds had time- and concentration-dependent cysticidal activity. Particularly, compounds TS-12, TS-19, and TS-20 (EC₅₀ values 0.58, 1.02, and 0.80 µM, respectively) were equipotent to albendazole sulfoxide (EC₅₀ = 0.68 µM). However, TS-12 compounds only cause a slight inhibition of <i>Ts</i>TIM (<40% at 1000 µM), suggested that another drug target is implicated in the biological effects. <b>Conclusions:</b> These results demonstrated that quinoxaline 1,4-di-<i>N</i>-oxide is a scaffold to develop new and more potent antitaeniasis agents, although it is necessary to explore other pharmacological targets to understand their mode of action.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carotenoids for Antiaging: Nutraceutical, Pharmaceutical, and Cosmeceutical Applications.","authors":"Mariia Shanaida, Olha Mykhailenko, Roman Lysiuk, Nataliia Hudz, Radosław Balwierz, Arkadii Shulhai, Nataliya Shapovalova, Volodymyr Shanaida, Geir Bjørklund","doi":"10.3390/ph18030403","DOIUrl":"10.3390/ph18030403","url":null,"abstract":"<p><p><b>Background</b>: Carotenoids are bioactive tetraterpenoid C40 pigments that are actively synthesized by plants, bacteria, and fungi. Compounds such as <i>α</i>-carotene, <i>β</i>-carotene, lycopene, lutein, astaxanthin, <i>β</i>-cryptoxanthin, fucoxanthin, and zeaxanthin have attracted increasing attention for their antiaging properties. They exhibit antioxidant, neuroprotective, and anti-inflammatory properties, contributing to the prevention and treatment of age-related diseases. <b>Objectives</b>: The aim of this study was to comprehensively analyze the pharmacological potential and biological mechanisms of carotenoids associated with age-related disorders and to evaluate their application in nutraceuticals, pharmaceuticals, and cosmeceuticals. <b>Methods</b>: A systematic review of studies published over the past two decades was conducted using the databases PubMed, Scopus, and Web of Science. The selection criteria included clinical, in silico, in vivo, and in vitro studies investigating the pharmacological and therapeutic effects of carotenoids. <b>Results</b>: Carotenoids demonstrate a variety of health benefits, including the prevention of age-related macular degeneration, cancer, cognitive decline, metabolic disorders, and skin aging. Their role in nutraceuticals is well supported by their ability to modulate oxidative stress and inflammatory pathways. In pharmaceuticals, carotenoids show promising results in formulations targeting neurodegenerative diseases and metabolic disorders. In cosmeceuticals, they improve skin health by protecting it against UV radiation and oxidative damage. However, bioavailability, optimal dosages, toxicity, and interactions with other bioactive compounds remain critical factors to maximize therapeutic efficacy and still require careful evaluation by scientists. <b>Conclusions</b>: Carotenoids are promising bioactive compounds for antiaging interventions with potential applications in a variety of fields. Further research is needed to optimize their formulas, improve bioavailability, and confirm their long-term safety and effectiveness, especially in the aging population.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Frankincense Oil on Wound Healing: Downregulating Caspase-3 Expression to Facilitate the Transition from the Inflammatory to Proliferative Phase.","authors":"Krishnaraju Venkatesan, Durgaramani Sivadasan, Moufida Abderrahmen Al Weslati, Mohammed Gayasuddin Mouid, Manoj Goyal, Monika Bansal, Mohamed El-Dosoky Mohamed Salama, Syed Azizullah Ghori, Fazil Ahmad","doi":"10.3390/ph18030407","DOIUrl":"10.3390/ph18030407","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Wound healing is a complex process involving inflammation, oxidative stress, immune modulation, and tissue regeneration. Frankincense essential oil (FEO), derived from <i>Boswellia</i> species, is known for its anti-inflammatory, antioxidant, and therapeutic properties. This study investigates the protective effects of FEO in an excision wound model in rats, focusing on oxidative stress reduction, inflammatory cytokine modulation, and caspase-3 regulation. <b>Methods:</b> The chemical composition of FEO was analyzed using gas chromatography-mass spectrometry (GC-MS). Rats with excision wounds were treated with FEO, and its efficacy was assessed using biochemical and histological analyses. Caspase-3 expression, IL-1β, TNF-α, and CD68 levels were measured, along with oxidative stress markers. Wound contraction, epithelialization and collagen synthesis were also evaluated. Immunohistochemical and histopathological assessments were performed to analyze inflammatory infiltration and tissue remodeling. <b>Results:</b> FEO, rich in <i>alpha-phellandrene</i> (10.52%) and <i>limonene</i> (7.31%), significantly downregulated caspase-3, reducing apoptosis in the wound environment. It also lowered IL-1β and TNF-α levels, confirming anti-inflammatory effects. Additionally, FEO modulated CD68 expression, shifting the wound environment from inflammatory to healing. The oil antioxidant activity reduced oxidative stress, limiting caspase-3-mediated apoptosis and enhancing cell survival. FEO treatment accelerated wound contraction, improved epithelialization, and increased collagen synthesis. Histological analysis revealed reduced inflammatory infiltration and enhanced tissue remodeling. <b>Conclusions:</b> FEO integrates anti-inflammatory, antioxidant, and anti-apoptotic mechanisms to promote wound healing and tissue repair. Its ability to modulate caspase-3, IL-1β, TNF-α, CD68, and oxidative stress markers along with its major constituents such as <i>alpha-phellandrene</i> and <i>limonene</i> highlights its potential as a natural therapeutic agent for wound management and regenerative medicine.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic and Molecular Insights into Empagliflozin's Role in Ferroptosis and Inflammation Trajectories in Acetaminophen-Induced Hepatotoxicity.","authors":"Aisha Alhaddad, Esraa M Mosalam, Hind S AboShabaan, Amany Said Sallam, Marwa M Mahfouz, Enas Elhosary, Asmaa A Mohammed, Ebtehal M Metwally, Moataz A Shaldam, Mai El-Sayed Ghoneim","doi":"10.3390/ph18030405","DOIUrl":"10.3390/ph18030405","url":null,"abstract":"<p><p><b>Background:</b> Acetaminophen (APAP)-induced acute liver injury (ALI) is increasingly becoming a public health issue with high rate of morbidity and mortality. Therefore, there is a critical demand for finding protective modalities by understanding the underlying proposed mechanisms including, but not limited to, ferroptosis and inflammation. <b>Objectives:</b> This study seeks to investigate the possible hepatoprotective effect of empagliflozin (EMPA) against APAP-induced ALI through modulation of ferroptosis and inflammatory cascades. <b>Methods:</b> Mice were allocated into the following five groups: vehicle control, APAP, EMPA 10, EMPA 20 (10 and 20 mg/kg/day, respectively, P.O.), and N-acetylcysteine (NAC, hepatoprotective agent against APAP-induced ALI). The hepatic injury was detected by determining liver enzymes and by histopathological examination. Inflammation, oxidative stress, apoptosis, and ferroptosis were also evaluated. <b>Results:</b> The APAP group showed an elevated level of hepatic enzymes with disrupted hepatic architecture. This toxicity was promoted by inflammation, oxidative stress, apoptosis, and ferroptosis, as indicated by elevated cytokines, lipid peroxidation, reduced antioxidants, increased caspase-3, decreased Bcl-2, and activation of the NF-κB/STAT3/hepcidin pathway. Pretreatment with EMPA remarkably reversed these features, which was reflected by restoration of the histoarchitecture of hepatic tissue, but the higher dose of EMPA was more efficient. <b>Conclusions:</b> APAP can induce ALI through initiation of inflammatory and oxidative conditions, which favor ferroptosis. EMPA hindered these unfavorable consequences; an outcome which indicates its anti-inflammatory, antioxidant, anti-apoptotic, and anti-ferroptotic effects. This modulatory action advocated EMPA as a potential hepatoprotective agent.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Effects of Low-Frequency Ultrasound and Therapeutic Agents on Endothelial and Renal Cells: Emphasis on Cell Functionality, Oxidative Stress, and Inflammatory Markers.","authors":"Ieva Čiapienė, Joris Vėžys, Vaiva Lesauskaitė, Indrė Matulevičiūtė, Ugnė Meškauskaitė, Vilius Skipskis, Arvydas Strazdauskas, Sonata Trumbeckaitė, Algimantas Bubulis, Vytautas Jūrėnas, Vytautas Ostaševičius, Vytenis Tamakauskas, Vacis Tatarūnas","doi":"10.3390/ph18030404","DOIUrl":"10.3390/ph18030404","url":null,"abstract":"<p><p><b>Background:</b> Ischemic heart disease remains the leading cause of death worldwide, with coronary microvascular dysfunction (CMD) as a key complication after ST-elevation myocardial infarction (STEMI). Endothelial dysfunction contributes to CMD, impairing vascular tone and increasing inflammation. While angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) aid vascular health, their efficacy may improve with therapeutic ultrasound, which enhances drug delivery and endothelial response. This study explores the combined effects of ultrasound and pharmacological treatment on the ACE axis and inflammation in endothelial and renal cells. <b>Methods:</b> Human umbilical vein endothelial cells (HUVECs) and human renal proximal tubular epithelial cell line RPTEC/TERT1 were treated with captopril, losartan, and dexamethasone, alone or combined with low-frequency ultrasound (LFU). Cell viability and wound-healing assays assessed cellular function, while nitric oxide (NO) and reactive oxygen species (ROS) assays were used to evaluate redox signaling. Gene expression related to the ACE axis, inflammation, and vascular and renal cell function was analyzed via qPCR. <b>Results:</b> Captopril and losartan combined with LFU improved endothelial cell viability, wound healing, and NO production at various concentrations, whereas only losartan with LFU enhanced cell viability and wound healing in renal cells. Dexamethasone with LFU increased ROS levels and had variable effects on RPTEC/TERT1 cell survival. Gene expression analysis showed that LFU alone reduced pro-inflammatory markers <i>VCAM-1</i>, <i>ICAM-1</i>, and <i>PTGS2</i> in captopril-treated HUVECs and similarly affected <i>CYP4F2</i> in losartan-treated HUVECs. LFU also decreased <i>PTGS2</i> expression at higher dexamethasone concentrations. In RPTEC/TERT1 cells, LFU alone did not impact <i>SGLT2</i> or <i>GGT1</i> expression, but captopril with LFU downregulated <i>GGT1</i>, and dexamethasone with LFU upregulated <i>SGLT2</i> at higher concentrations. <b>Conclusions:</b> This study demonstrates that LFU enhances the effects of RAS inhibitors by promoting NO synthesis and reducing oxidative stress, while its combination with dexamethasone may have variable, potentially cytotoxic effects on renal cells. Gene expression patterns suggest LFU's anti-inflammatory potential and its role in modulating drug efficacy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing Multi-Dimensional LC-MS Systems for Versatile Workflows to Analyze Therapeutic Antibodies at Different Molecular Levels in Routine Operations.","authors":"Katrin Heinrich, Sina Hoelterhoff, Saban Oezipek, Martin Winter, Tobias Rainer, Lucas Hourtoulle, Ingrid Grunert, Tobias Graf, Michael Leiss, Anja Bathke","doi":"10.3390/ph18030401","DOIUrl":"10.3390/ph18030401","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Multi-dimensional liquid chromatography coupled with mass spectrometry (mD-LC-MS) has emerged as a powerful technique for the in-depth characterization of biopharmaceuticals by assessing chromatographically resolved product variants in a streamlined and semi-automated manner. The study aims to demystify and enhance the accessibility to this powerful but inherently complex technique by detailing a robust and user-friendly instrument platform, allowing analysts to switch seamlessly between intact, subunit, and peptide mapping workflows. <b>Methods:</b> Starting from a commercially available Two-Dimensional Liquid Chromatography (2D-LC) system, we introduce specific hardware and software extensions leading to two versatile mD-LC-MS setups, in slightly different configurations. The technique's efficacy is demonstrated through a case study on a cation exchange chromatography method assessing the charge variants of a bispecific antibody, isolating peak(s) of interest, followed by online sample processing, including reduction and enzymatic digestion, and subsequently mass spectrometry analysis. <b>Results:</b> The accuracy and reproducibility of both mD-LC-MS setups proposed in this study were successfully tested. Despite the complex peak patterns in the first dimension, the systems were equally effective in identifying and quantifying the underlying product species. This case study highlights the routine usability of mD-LC-MS technology for the characterization of (ultra) high-performance liquid chromatography (UHPLC) of therapeutic biomolecule. <b>Conclusions:</b> The demonstrated reliability and accuracy underscore the practicality of mD-LC-MS for routine use in biopharmaceutical analysis. Our detailed description of the mD-LC-MS systems and insights simplify access to this advanced technology for a broader scientific community, regardless of expertise level, and lower the entry barrier for its use in various research and industrial settings.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combating Antibiotic Resistance: Mechanisms, Multidrug-Resistant Pathogens, and Novel Therapeutic Approaches: An Updated Review.","authors":"Mostafa E Elshobary, Nadia K Badawy, Yara Ashraf, Asmaa A Zatioun, Hagar H Masriya, Mohamed M Ammar, Nourhan A Mohamed, Sohaila Mourad, Abdelrahman M Assy","doi":"10.3390/ph18030402","DOIUrl":"10.3390/ph18030402","url":null,"abstract":"<p><p>The escalating global health crisis of antibiotic resistance, driven by the rapid emergence of multidrug-resistant (MDR) bacterial pathogens, necessitates urgent and innovative countermeasures. This review comprehensively examines the diverse mechanisms employed by bacteria to evade antibiotic action, including alterations in cell membrane permeability, efflux pump overexpression, biofilm formation, target site modifications, and the enzymatic degradation of antibiotics. Specific focus is given to membrane transport systems such as ATP-binding cassette (ABC) transporters, resistance-nodulation-division (RND) efflux pumps, major facilitator superfamily (MFS) transporters, multidrug and toxic compound extrusion (MATE) systems, small multidrug resistance (SMR) families, and proteobacterial antimicrobial compound efflux (PACE) families. Additionally, the review explores the global burden of MDR pathogens and evaluates emerging therapeutic strategies, including quorum quenching (QQ), probiotics, postbiotics, synbiotics, antimicrobial peptides (AMPs), stem cell applications, immunotherapy, antibacterial photodynamic therapy (aPDT), and bacteriophage. Furthermore, this review discusses novel antimicrobial agents, such as animal-venom-derived compounds and nanobiotics, as promising alternatives to conventional antibiotics. The interplay between clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) in bacterial adaptive immunity is analyzed, revealing opportunities for targeted genetic interventions. By synthesizing current advancements and emerging strategies, this review underscores the necessity of interdisciplinary collaboration among biomedical scientists, researchers, and the pharmaceutical industry to drive the development of novel antibacterial agents. Ultimately, this comprehensive analysis provides a roadmap for future research, emphasizing the urgent need for sustainable and cooperative approaches to combat antibiotic resistance and safeguard global health.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}