Future Journal of Pharmaceutical Sciences最新文献

{"title":"Exploring the gut microbiome of Mugil cephalus for antibacterial agents using liquid chromatography","authors":"Noor Akbar,&nbsp;Ruqaiyyah Siddiqui,&nbsp;Mohamed Y. Abouleish,&nbsp;Ahmad M. Alharbi,&nbsp;Ayman Alhazmi,&nbsp;Mazen Almehmadi,&nbsp;Naveed Ahmed Khan","doi":"10.1186/s43094-026-00968-x","DOIUrl":"10.1186/s43094-026-00968-x","url":null,"abstract":"<div><p>Due to the global challenge of antimicrobial resistance, there is an urgent need for the development of new drugs to combat infections. We hypothesize that bacteria isolated from untapped sources, namely from the gut microbiome of species living in unhygienic environments likely produce antimicrobials. Herein, gut bacteria from <i>Mugil cephalus</i>, an Egyptian fish, were isolated and identified using 16S rDNA amplification and sequencing. The isolated bacterial colonies were cultured in minimal media, and conditioned media containing metabolites were prepared and tested against selected Gram-positive and Gram-negative multiple drug-resistant bacteria using antibacterial assays. The conditioned media were also tested against  human colorectal cancer (HCT-116) cells using lactate dehydrogenase assays. Results from antibacterial analysis revealed that conditioned media from bacterial strain: <i>Bacillus aerophilus</i> and <i>Staphylococcus xylosus</i> showed broad-spectrum antibacterial effects. In particular, the conditioned media from bacterial strain: <i>Bacillus aerophilus</i> significantly inhibited bacterial viability. The conditioned media containing metabolites from bacterial strains produced minimal cytotoxicity toward human cells. Mass spectrometry analysis revealed several antibacterial, antifungal, flavonoids, neurotransmitters, sphingolipids, steroids and anticancer compounds. These results are indicative that bacteria from unique environments are a potential source to isolate molecule(s) with antibacterial properties, albeit in vivo studies are needed to validate these findings.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00968-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148236439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative study of the bioavailability of two coenzyme Q10 products following single-dose and 3-week oral administration in healthy adults","authors":"Zala Jenko Pražnikar,&nbsp;Nina Mohorko,&nbsp;Vasilij Valenčič,&nbsp;Vasja Valetič,&nbsp;Dejan Gmajner,&nbsp;Marco Morosetti,&nbsp;Patrick Orlando,&nbsp;Ana Petelin","doi":"10.1186/s43094-026-00999-4","DOIUrl":"10.1186/s43094-026-00999-4","url":null,"abstract":"<div><h3>Background</h3><p>Coenzyme Q10 (CoQ10) is a widely used food supplement due to its potential therapeutic benefits, which largely depend on its bioavailability. This study compared the bioavailability of two CoQ10 formulations—unencapsulated ubiquinone (standard) and microencapsulated CoQ10 (BMT®)—in healthy adults following both acute and chronic oral administration, and examined their effects on selected metabolic parameters.</p><h3>Methods</h3><p>This randomized, two-way crossover trial included 25 healthy adult participants. Each received a single 100 mg dose of both formulations, as well as a 3-week daily regimen of 100 mg of one of the formulations. Bioavailability was assessed by calculating the area under the curve for plasma CoQ10 concentrations over 48 h after a single dose administration and over the 3-week supplementation period.</p><h3>Results</h3><p>The microencapsulated CoQ10 demonstrated significantly superior bioavailability at 6, 12, and 24 h, with an average fold increase of 1.8, 2.4, and 1.9, compared to standard. Following chronic supplementation, plasma CoQ10 concentrations increased by approximately 80% with standard and 95% with the microencapsulated formulation relative to baseline, while differences between formulations were no longer significant. A significant effect on vitamin D levels was also observed: microencapsulated CoQ10 led to higher vitamin D concentrations after 3 weeks (<i>P</i> = 0.001).</p><h3>Conclusion</h3><p>These results confirm the safety and superior acute bioavailability of microencapsulated CoQ10 and suggest possible broader metabolic benefits.</p><h3>Trial registration</h3><p>ClinicalTrials.gov (NCT06736366). Registered 11 December 2025, https://clinicaltrials.gov/study/NCT06736366#study-record-dates</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00999-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatographic method selection strategy for first-line antituberculosis fixed-dose combinations","authors":"Imad Osman Abu Reid","doi":"10.1186/s43094-026-00990-z","DOIUrl":"10.1186/s43094-026-00990-z","url":null,"abstract":"<div><h3>Background</h3><p>Fixed-dose combinations (FDCs) containing Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol remain the cornerstone of first-line antituberculosis therapy. However, their simultaneous chromatographic determination presents significant analytical challenges due to marked differences in lipophilicity (logP), ionization constants (pKa), chromophoric properties, chemical stability, and dose ratios. These disparities complicate retention control, selectivity optimization, peak symmetry, and detection sensitivity, particularly in stability-indicating method development.</p><h3>Main body</h3><p>This work outlines a mechanism-guided strategy for chromatographic method selection tailored to first-line antituberculosis FDCs. The approach integrates physicochemical profiling with rational selection of separation mode, stationary phase chemistry, mobile phase pH control, and detection strategy. Reversed-phase liquid chromatography (RP-LC) is justified as the primary separation mode due to its compatibility with ultraviolet and mass spectrometric detection, regulatory acceptance, and suitability for stability-indicating analysis. Stationary phase selection (e.g., base-deactivated or polar-embedded C18) is emphasized to minimize silanol interactions and compress the retention window between highly polar and lipophilic analytes. Buffered gradient elution under acidic conditions is recommended to balance retention, improve peak symmetry, and enhance robustness. Detection strategies are aligned with chromophoric disparities and dose imbalance, highlighting the complementary roles of diode array detection and LC–MS techniques. Special consideration is given to degradation pathways and interaction products, particularly under acidic conditions, necessitating forced degradation studies and peak purity assessment to ensure stability-indicating capability.</p><h3>Conclusion</h3><p>A mechanistically informed chromatographic selection strategy enables robust, selective, and stability-indicating simultaneous determination of first-line antituberculosis FDCs. Integrating physicochemical understanding with systematic optimization enhances method reliability, regulatory compliance, and analytical efficiency.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00990-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148010109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renoprotective action of rabeprazole and lansoprazole in gentamicin-induced nephrotoxicity: roles of oxidative stress, apoptosis, ER stress, and OCT2 expression","authors":"Khalid AlAzmi,&nbsp;Rehab M. Khedr,&nbsp;Elsayed K. El-Sayed,&nbsp;Mohamad Elbaz","doi":"10.1186/s43094-026-00980-1","DOIUrl":"10.1186/s43094-026-00980-1","url":null,"abstract":"<div><h3>Background</h3><p>Gentamicin (GNT)-induced nephrotoxicity involves oxidative stress, apoptosis, and enhanced renal accumulation, partly mediated by OCT2 transport activity. Proton pump inhibitors (PPIs) have been reported to exhibit nephroprotective actions beyond their gastric acid–suppressive effects. Accordingly, this study investigates the nephroprotective effects of rabeprazole (Rabe) and lansoprazole (Lanso) against GNT-induced nephrotoxicity in rats and explores their potential underlying mechanisms with particular focus on oxidative stress modulation, apoptotic signaling, endoplasmic reticulum (ER) stress regulation, and OCT2 expression. Rats were randomized into six groups: a saline control, a GNT group (100 mg/kg, <i>ip/</i> eight days), two groups receiving Rabe or Lanso alone (20 mg/kg, orally / eight days), and two groups receiving Rabe or Lanso one hour before GNT for eight days. On day nine, blood and kidney tissues were collected for biochemical, molecular, and histopathological assessment.</p><h3>Results</h3><p>Both PPIs improved renal function parameters, mitigated oxidative stress, and favorably influenced key apoptotic markers. They also attenuated ER stress indicators and modulated OCT2 expression, suggesting a potential role in limiting GNT-induced renal accumulation. Histopathological evaluation further supported these biochemical findings, showing noticeable preservation of renal tubular structure in PPI-treated rats. Both agents demonstrated nephroprotective effects in the current experimental setting; however, Lanso exhibited comparatively greater improvement in several evaluated parameters.</p><h3>Conclusions</h3><p>Our findings indicate that Rabe and Lanso may have promising nephroprotective potential against GNT-induced renal injury and warrant further preclinical validation and subsequent clinical assessment.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00980-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148009288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety profile of aromatase inhibitors combined with CDK4/6 inhibitors: a real-world analysis based on FAERS","authors":"Jun Zhou,&nbsp;Saisa Zhu,&nbsp;Jinlan Shan,&nbsp;Jingpei Long","doi":"10.1186/s43094-026-00989-6","DOIUrl":"10.1186/s43094-026-00989-6","url":null,"abstract":"<div><h3>Background</h3><p>The combination of a CDK4/6 inhibitor with an aromatase inhibitor (AI) is now a cornerstone first-line treatment. However, the comprehensive safety profile of this combination has not been fully characterized. The aim of this study was to evaluate the real-world safety profile of AIs combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in advanced breast cancer from the US FDA Adverse Event Reporting System (FAERS).</p><h3>Methods</h3><p>A retrospective pharmacovigilance study was conducted using FAERS data from 2015 to 2024. Disproportionality analyses were performed using four established algorithms (ROR, PRR, BCPNN, and MGPS) to detect safety signals for adverse events (AEs) at the System Organ Class (SOC) and Preferred Term (PT) levels. The time to onset (TTO) of AEs was analyzed using the Kruskal‒Wallis test, and risk factors for important medical events (IMEs) were identified via logistic regression.</p><h3>Results</h3><p>Among 19,746 patients treated with AIs, 3,739 (18.9%) received combination therapy. The analysis revealed a distinct AE profile for combination therapy, with hematological toxicity being the most prominent. Strong, consistent signals were detected for neutropenia (ROR = 143.57), anemia, and thrombocytopenia. Compared with AI monotherapy (60–90 days), combination therapy was associated with a significantly delayed median TTO of AEs (&gt; 180 days) (<i>P</i> &lt; 0.001), with significant variation among specific drug pairs. Logistic regression revealed older age (OR = 1.022 per year; <i>P</i> = 0.0003) and anastrozole use (vs. letrozole; OR = 1.876; <i>P</i> = 0.004) as independent risk factors for IMEs. Compared with abemaciclib, ribociclib (OR = 0.299; <i>P</i> &lt; 0.001) and palbociclib (OR = 0.595; <i>P</i> = 0.012) were associated with a significantly lower risk of IMEs.</p><h3>Discussion</h3><p>This large-scale real-world analysis confirms the significant hematological toxicity of the AI and CDK4/6 inhibitor combination therapy and reveals a previously underappreciated delay in AE onset.</p><h3>Conclusion</h3><p>This study reveals that the risk of serious outcomes is not uniform but is significantly influenced by patient age and the specific choice of AI and CDK4/6 inhibitor, underscoring the need for a personalized, risk-adapted approach to treatment selection and monitoring.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00989-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148009303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening, designing, and validation of novel siRNAs to target GLUT-3: new avenue of targeted therapy for solid tumors","authors":"Harvansh Kumar,&nbsp;Neeraj Kumar Shrivastava,&nbsp;Pratibha Verma,&nbsp;Jyoti Singh,&nbsp;Mohd Nazam Ansari,&nbsp;Abdulaziz S. Saeedan,&nbsp;Anurag Kumar,&nbsp;Gaurav Kaithwas","doi":"10.1186/s43094-026-00966-z","DOIUrl":"10.1186/s43094-026-00966-z","url":null,"abstract":"<div><p>Glucose transporters-3 (GLUT-3) are implicated in the altered glucose uptake of cancer cells, and the study investigates the potential of silencing GLUT-3 using small interfering RNA (siRNA). A set of in silico tools was employed to design and validate seven optimal siRNAs (G1, G2, G3, G4, G5, G6, G7) against GLUT-3. The off-target analysis was performed using the Basic Local Alignment Search Tool (BLASTn), while secondary structure prediction was performed using RNAfold. The designed siRNAs' thermodynamic stability and GC content were studied using the OligoCalc web server. Binding energies between siRNAs and human argonaute-2 (hAgo2) were calculated through the HDOCK web server. Based on the off-target elimination, secondary structure formation, thermodynamic stability, and binding with hAgo2 protein, we considered G1 and G7 as potential candidates for further evaluation. The AMBER99SB force field was employed to investigate the structural stability of the siRNA–hAgo2 complex via molecular dynamics (MD) simulations. Post-simulation analyses included: Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), and hydrogen bond evaluations. The molecular mechanics Poisson–Boltzmann surface area (MMPBSA) assay was used to assess the binding free energy of the siRNA–hAgo2 complex with the selected siRNA candidates. The findings suggested G5 (AGAAAUAGAAACUACAGUG) as a promising siRNA candidate for targeting GLUT-3. Given its potential effectiveness, further evaluation is warranted to assess its suitability for therapeutic applications.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00966-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chitosan-based nano-formulation of berberine isolated from Berberis lycium enhances sustained anticancer effects in MCF-7 cells","authors":"Monica Sangral,&nbsp;Makul Mahato,&nbsp;Ankita Singh,&nbsp;Ashutosh Gupta,&nbsp;Madhulika Bhagat","doi":"10.1186/s43094-026-00986-9","DOIUrl":"10.1186/s43094-026-00986-9","url":null,"abstract":"<div><h3>Background</h3><p>Breast cancer remains a major health challenge with limited targeted therapies. Berberine (BBR), an alkaloid from <i>Berberis lycium</i>, has promising pharmacological effects but suffers from poor solubility and bioavailability. This study encapsulates BBR in chitosan nanoparticles to enhance solubility, enable sustained release, and improve its therapeutic efficacy against breast cancer, focusing on its potential mechanism of inducing cell death.</p><h3>Results</h3><p>Berberine (4.2% w/w) was isolated from <i>Berberis lycium</i> from Rajouri, Jammu &amp; Kashmir. The resulting chitosan nanoparticles (BBRC) averaged 114 nm, with a PDI of 0.4, zeta potential of 18.8 mV, 96 ± 3.25% encapsulation efficiency, and 4.8 ± 3.5% loading capacity. MCF-7 breast cancer cell line demonstrated significant sensitivity to BBR (IC₅₀: 8.4 ± 1.4 µg/mL) compared to nano-berberine (IC₅₀: 9.21 ± 2.1 µg/mL) (p &lt; 0.05). In vitro, BBRC showed sustained berberine release over seven days and enhanced effects on MCF-7 cell proliferation, nuclear morphology, cell cycle, and apoptosis compared to free berberine. To the best of our knowledge, this study is among the first to evaluate time-dependent differences between nano- and pure berberine. Docking showed strong binding to MCL-1 (score -7.6 kcal/mol), and ADMET analysis predicted favourable pharmacokinetic and safety profiles for the nano-formulation.</p><h3>Conclusions</h3><p>Chitosan-encapsulated nano-berberine showed enhanced solubility, sustained release, and improved anticancer activity against breast cancer, highlighting its potential as an effective delivery system.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00986-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148008685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico and in vivo targeting of Wnt/β-catenin/GSK-3β and redox pathways: geraniol–CoQ10 as a novel cardioprotective duo against I/R injury","authors":"Nermein F. El Sayed,&nbsp;Azza Sayed Mohamed Awad,&nbsp;Iten M. Fawzy,&nbsp;Hesham Mohamed Mahmoud,&nbsp;Hanan S. El-Abhar","doi":"10.1186/s43094-026-00987-8","DOIUrl":"10.1186/s43094-026-00987-8","url":null,"abstract":"<div><h3>Background</h3><p>Although statins confer cardioprotection via HMG-CoA reductase inhibition, they are also known to reduce CoQ10 biosynthesis. In light of previous reports suggesting that geraniol, a natural monoterpene with pleiotropic cardioprotective effects, may intersect with the mevalonate pathway, we hypothesized that combining geraniol with CoQ10 could yield enhanced cardioprotective benefits. Using in silico analyses and a rat model of myocardial ischemia/reperfusion (I/R) injury (30-min LAD occlusion followed by 120-min reperfusion with continuous ECG monitoring), we evaluated geraniol alone and with CoQ10. Male Wistar rats were allocated into five groups: sham, I/R, geraniol + I/R, CoQ10 + I/R, and geraniol + CoQ10 + I/R.</p><h3>Results</h3><p>Preconditioning with geraniol and/or CoQ10 significantly decreased infarct size relative to the area at risk, preserved myocardial histoarchitecture, and mitigated cardiac biomarkers (CK-MB, LDH, cTn-I) and ST-segment elevation. Molecularly, treatments suppressed GSK-3β, a pivotal mediator of I/R injury, via activation of the Wnt/β-catenin pathway, while reinforcing antioxidant defenses (SOD, GSH) and reducing lipid peroxidation. They also inhibited inflammatory mediators (pSer536-NF-κB, TNF-α), neutrophilic infiltration (ICAM-1, MPO), curtailed caspase-3, and elevated Bcl-2, reflecting strong anti-inflammatory and antiapoptotic actions. In silico docking also predicted the ability of geraniol and CoQ10 to interact with GSK-3β and NF-κB. Notably, the combination therapy conferred the greatest protection.</p><h3>Conclusion</h3><p>Overall, these findings identify geraniol and CoQ10, particularly in combination, as promising cardioprotective agents against I/R injury through modulation of Wnt/GSK-3β/β-catenin signaling and associated antioxidative, anti-inflammatory, and antiapoptotic pathways.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00987-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR7/8 agonist HYBRID2 as a dual-action compound against Leishmania donovani: antiparasitic and immunomodulatory effects","authors":"Sandeep Kaur,&nbsp;Kushvinder Kumar,&nbsp;Shivani Thakur,&nbsp;Deepak B. Salunke,&nbsp;Sukhbir Kaur","doi":"10.1186/s43094-026-00988-7","DOIUrl":"10.1186/s43094-026-00988-7","url":null,"abstract":"<div><h3>Background</h3><p>Visceral leishmaniasis (VL) remains a fatal parasitic disease with limited treatment options and growing drug resistance. To address this challenge, we synthesized and characterized HYBRID2, an imidazoquinoline-based TLR7/8 agonist and explored its untapped potential against <i>Leishmania</i> through in vitro and in silico studies.</p><h3>Results</h3><p>HYBRID2 effectively eliminated both promastigote and intracellular amastigote forms of <i>Leishmania donovani</i> (Promastigote IC₅₀: 6.50 ± 2.20 µM; Amastigote IC₅₀: 7.56 ± 1.58 µM), while exhibiting moderate cytotoxicity (Raw macrophages CC₅₀: 42.30 ± 3.88 µM; HeLa CC₅₀: 36.66 ± 4.37 µM). The mechanistic investigation confirmed that HYBRID2 induced a marked arrest of the parasite cell cycle in the sub-G₀/G₁ population (84.64% <i>vs.</i> 7.23% in untreated; <i>p</i> &lt; 0.0001), significantly inhibited parasite growth, and robustly enhanced Reactive Oxygen Species (ROS) (607.66 mean fluorescence intensity; <i>p</i> &lt; 0.0001) and Nitric Oxide (NO) production (22.53 ± 0.73 µM; <i>p</i> &lt; 0.0001), indicating a strong immunomodulatory role associated through its dual TLR7/8 agonist activity. Interestingly, the in silico studies and ADMET analyses of HYBRID2 suggested strong multi-target interactions, with the strongest affinity observed for anti-leishmanial drug target trypanothione reductase, alongside favorable pharmacokinetic properties.</p><h3>Conclusions</h3><p>This study highlights an innovative and disease-relevant application of a dual TLR7/8 agonist with a distinct immunopharmacological profile, reinforced by strong in silico target engagement, underscoring its potential for host-directed therapeutic development against visceral leishmaniasis.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture><span>The alternative text for this image may have been generated using AI.</span></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00988-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D bioprinting: current status and future prospects in tissue and organ regeneration","authors":"M. Selvakumar,&nbsp;J. Dhanasekar,&nbsp;S. Nandhakumaran,&nbsp;T. Sudhamani","doi":"10.1186/s43094-026-00982-z","DOIUrl":"10.1186/s43094-026-00982-z","url":null,"abstract":"<div><p>Three-dimensional (3D) bioprinting has emerged as a transformative technology in tissue engineering and regenerative medicine, offering innovative solutions for the fabrication of complex biological structures. By utilizing bioinks composed of living cells and biomaterials, 3D bioprinting enables the precise layer-by-layer construction of functional tissues and organs. This review explores the latest advancements in bioprinting techniques, including inkjet-based, extrusion-based, laser-assisted, and stereolithography-based methods. Key biomaterials used in bioprinting, such as hydrogels, natural and synthetic polymers, and composite materials, are discussed in relation to their biocompatibility and mechanical properties. The applications of 3D bioprinting in tissue regeneration, wound healing, drug testing, and organ transplantation are examined, highlighting its potential to address critical shortages in donor organs. Despite its promising benefits, challenges such as vascularization, cell viability, scalability, and regulatory hurdles remain significant barriers to clinical translation. Future directions in 3D bioprinting, including the integration of artificial intelligence, advanced bioinks, and personalized medicine approaches, are also explored. This review provides a comprehensive overview of the current status and prospects of 3D bioprinting, emphasizing its transformative potential in biomedical sciences.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00982-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}