Future Journal of Pharmaceutical Sciences最新文献

{"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}

{"title":"Enhanced antidiabetic efficacy and bioavailability of curcumin-loaded sporopollenin microcapsules in a type 2 diabetes rat model","authors":"Noha M. Meligi,&nbsp;Noura A. Saad,&nbsp;Bahaa K. A. Abdel-Salam,&nbsp;Amro K. F. Dyab,&nbsp;Diaa B. Al-Azhary","doi":"10.1186/s43094-026-00977-w","DOIUrl":"10.1186/s43094-026-00977-w","url":null,"abstract":"<div><h3>Background</h3><p>The rising global prevalence of type 2 diabetes mellitus (T2DM) necessitates the identification of efficient medications for its management. Curcumin (Cur), the principal curcuminoid found in turmeric, exhibits numerous beneficial effects on T2DM. The application of Cur for the treatment of T2DM presents several limitations, including inadequate penetration, decreased stability, poor solubility, and low bioavailability. Consequently, a versatile protective Cur encapsulation system is needed to address its natural instability. This study presents the application of <i>Lycopodium clavatum</i> sporopollenin (LCS) microcapsules, derived from natural micrometer-sized raw pollens, for Cur microencapsulation to enhance curcumin efficacy in an experimental rat model of T2DM.</p><h3>Results</h3><p>Over a 4-week treatment, the high-fat diet/Streptozotocin (HFD/STZ)-induced diabetic rats administered Cur-loaded LCS reduced FBG by 60%, decreased serum TNF-α by 20%, and increased IL-10 by 45% compared to curcumin diabetic rats. Furthermore, histological investigations of the kidney, pancreas, and liver revealed that Cur-loaded LCS ameliorated the organs' degenerative alterations in diabetic rats.</p><h3>Conclusion</h3><p>The current study demonstrates that microencapsulation of Cur within pollen-derived biomaterials facilitates Cur delivery and improves bioavailability, establishing it as a promising method for addressing complications related to T2DM.</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":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00977-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829617","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":"PARP-1 inhibitors in cancer therapy: design, molecular modeling, structure–activity relationships, and clinical advances","authors":"Rosine Abdullah,&nbsp;Menna A. Ewida,&nbsp;Iten M. Fawzy,&nbsp;Mohamed Hagras,&nbsp;Hanan M. Refaat,&nbsp;Nasser S. M. Ismail","doi":"10.1186/s43094-026-00984-x","DOIUrl":"10.1186/s43094-026-00984-x","url":null,"abstract":"<div><p>Poly (ADP-ribose) polymerase-1 (PARP-1) is an enzyme that plays a pivotal role in DNA repair and the maintenance of genomic stability. The discovery of synthetic lethality in tumors with homologous recombination deficiencies, particularly BRCA1/2 mutations, has validated PARP inhibitors as an important class of targeted anticancer agents. Several inhibitors, including olaparib, rucaparib, niraparib, and talazoparib, are now clinically approved and have significantly demonstrated clinical benefit in selected patient populations. This review discusses the structural development of PARP-1 inhibitors from classical NAD analogues to newer non-NAD and dual-target compounds, with emphasis on structure–activity relationships (SAR) and molecular modeling studies. Key binding interactions within the PARP-1 catalytic domain and factors influencing selectivity and potency are highlighted, together with emerging strategies aimed at overcoming drug resistance and improving therapeutic effectiveness. Despite notable clinical success, challenges such as adverse effects, acquired resistance, and limited activity in certain tumor types remain. Continued research and development in rational drug design and biomarker-driven therapy is expected to enhance the precision and long-term benefit of PARP-1-targeted treatments.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00984-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796656","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":"Analytical quality by design (AQbD) approach for the simultaneous quantification of FDC in a cardiovascular drug by RP-HPLC method","authors":"Varsha Thorat,&nbsp;Sudhakar Alave,&nbsp;Vijay Bagul","doi":"10.1186/s43094-026-00985-w","DOIUrl":"10.1186/s43094-026-00985-w","url":null,"abstract":"<div><h3>Background</h3><p>A sustainable and stability-indicating reversed-phase high-pressure liquid chromatography (RP-HPLC) method has been developed for the simultaneous estimation of chlorthalidone (CHL), Amlodipine (AML), and olmesartan medoxomil (OLM) in a combined cardiovascular dosage form by implementing an Analytical Quality by Design (AQbD) approach.</p><h3>Methods</h3><p>The RP-HPLC system employed a Sunniest C18 column (150 mm × 4.6 mm, 5.0 μm). The mobile phase consisted of 0.1% triethylamine in water (pH 2.4) and ethanol in a ratio of (65:35 v/v). At a flow rate of 1.5 mL/min. Detection was carried out at 245 nm using a photodiode array detector. Method optimization was performed using a Central composite design (CCD) under the AQbD framework. Forced degradation studies were conducted under acid, base, oxidative, thermal, and photolytic conditions to assess the method’s stability-indicating capability.</p><h3>Results</h3><p>The method showed good linearity in the 50–150% of test concentration with correlation coefficients (r²) exceeding 0.99 for all analytes. The method precision  was found 98.9% for CHL and 101.4% for both AML and OLM. Forced degradation studies confirmed the method’s ability to resolve the active pharmaceutical ingredients from their degradation products. Well-separated, spectrally pure peaks were obtained for all analytes under all stress conditions, as confirmed by peak purity values greater than 0.950, indicating no interference from degradation products. The method demonstrated accuracy, precision, specificity, robustness as per the International Conference on Harmonization guidelines. Environmental sustainability was evaluated with GAPI (77), AMGS123, AGREEprep (0.69), and AGREE (0.81) scores, confirming its eco-friendly nature.</p><h3>Conclusions</h3><p>The integrated approach reduced solvent consumption, waste generation, and energy usage, supporting sustainable analysis. The method, validated as per ICH Q2(R2) guidelines, exhibited excellent linearity, precision, accuracy, specificity, robustness, and ruggedness. Forced degradation studies confirmed its stability-indicating capability. The present study highlights the need for incorporating antioxidants and implementing precautions against acidic and alkaline degradation, along with adopting proper packaging and storage strategies to enhance the stability of CHL, OLM, and AML in formulations prone to degradation..</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":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00985-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796563","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":"Antioxidant adjuvants as a strategy to combat multidrug-resistant gram-negative bacteria: mechanistic insights and translational perspectives","authors":"Yasmin Magdy Hamza,&nbsp;Eman Mohamed Elmokadem,&nbsp;Marwa Adel Ahmed,&nbsp;Aalaa K. Shata,&nbsp;Hayam Ateyya","doi":"10.1186/s43094-026-00969-w","DOIUrl":"10.1186/s43094-026-00969-w","url":null,"abstract":"<div><h3>Background</h3><p>Antimicrobial resistance (AMR) is a major global health threat. Multidrug-resistant (MDR) Gram-negative pathogens—including <i>Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa,</i> and <i>Acinetobacter baumannii</i>—pose serious therapeutic challenges in both hospital and community settings. These organisms possess diverse resistance mechanisms such as reduced outer membrane permeability, efflux pump overexpression, biofilm formation, enzymatic drug inactivation, and horizontal gene transfer. The global spread of mobile resistance determinants, including <i>mcr</i> genes and carbapenemases, has compromised the efficacy of last-resort antibiotics such as colistin and carbapenems, highlighting the need for alternative therapeutic strategies.</p><h3>Main body</h3><p>Given the limited development of new antibiotics, antioxidant-based non-antibiotic adjuvants have emerged as a promising strategy to restore antimicrobial activity. Bioactive compounds—including flavonoids, polyphenols, melatonin, vitamins, and thiol-containing molecules—exert multiple effects on bacterial physiology. These include disruption of membrane integrity, inhibition of efflux pumps, modulation of redox homeostasis, interference with quorum sensing, and suppression of biofilm formation. Some antioxidants also display host-directed immunomodulatory effects that may reduce inflammation and oxidative tissue injury during infection. Recent preclinical studies (2020–2025) demonstrate synergistic activity between antioxidant adjuvants and conventional antibiotics such as colistin, carbapenems, aminoglycosides, and fluoroquinolones. These combinations can reduce minimum inhibitory concentrations, enhance bacterial killing, and restore antibiotic susceptibility in resistant strains. However, clinical translation remains limited due to challenges including pharmacokinetic variability, uncertain dose optimization, potential drug interactions, and the lack of well-designed clinical trials.</p><h3>Conclusion</h3><p>Antioxidant adjuvants represent a mechanistically diverse strategy for combating MDR Gram-negative infections and restoring antibiotic efficacy. Future progress will require rigorous pharmacokinetic and pharmacodynamic evaluation, standardized synergy testing, and well-designed clinical trials to confirm safety, efficacy, and clinical applicability.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00969-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737377","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":"Zinc and selenium in the management of subclinical hypothyroidism: mechanistic insights, clinical evidence, and translational perspectives","authors":"Farida N. Abdelrazek,&nbsp;Eman Mohamed Elmokadem,&nbsp;Hisham Abdelhady,&nbsp;Hayam Ateyya","doi":"10.1186/s43094-026-00972-1","DOIUrl":"10.1186/s43094-026-00972-1","url":null,"abstract":"<div><p>Subclinical hypothyroidism (SCH) is a prevalent endocrine disorder characterized by elevated serum thyroid-stimulating hormone (TSH) concentrations in the presence of normal circulating free thyroxine (fT4). Although frequently asymptomatic, SCH has been increasingly associated with adverse metabolic, cardiovascular, reproductive, and neurocognitive outcomes, as well as progression to overt hypothyroidism. Therapeutic decision-making remains controversial, particularly in individuals with mild TSH elevation below 10 mIU/L, where the clinical benefit of levothyroxine replacement therapy is inconsistent. Growing attention has therefore been directed toward modifiable metabolic contributors to thyroid dysfunction, including micronutrient status. Zinc and selenium are essential trace elements that participate in thyroid hormone synthesis, peripheral activation, receptor-mediated signaling, antioxidant defense, and immune modulation. Zinc is critical for thyroid hormone receptor structure and hypothalamic–pituitary regulation, whereas selenium is incorporated into iodothyronine deiodinases and antioxidant selenoproteins that preserve thyrocyte integrity. This narrative review synthesizes current mechanistic and clinical evidence supporting the adjunctive role of zinc and selenium in the management of SCH. While emerging data suggest potential biochemical and immunological benefits, heterogeneity in study design and duration necessitates well-powered randomized trials to define optimal dosing strategies and long-term clinical outcomes.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00972-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737609","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":"Maintenance low-dose capecitabine versus observation in early-stage triple-negative breast cancer: a randomized controlled trial assessing safety with exploratory survival outcomes","authors":"Sarah Hamdy Ali,&nbsp;Enas Mohsen El Nadi,&nbsp;Abeer Mokhles Gadallah,&nbsp;Ahmad Mahrous Dewidar,&nbsp;Engy A. Wahsh,&nbsp;Ahmed Hassan Shaaban","doi":"10.1186/s43094-026-00964-1","DOIUrl":"10.1186/s43094-026-00964-1","url":null,"abstract":"<div><h3>Background</h3><p>Triple-negative breast cancer (TNBC) carries a worse prognosis primarily because it does not have specific targeted therapies and is biologically aggressive, leading to a great probability of early relapse, especially involving visceral sites. At present, standard chemotherapy is the only available treatment in the adjuvant setting for early-stage triple-negative breast cancer, creating a critical need for effective maintenance strategies to reduce relapse and death rates. This study was intended to assess the impact of maintenance low-dose capecitabine for females diagnosed with early triple-negative breast cancer on safety, disease-free survival, and overall survival following completion of all standard adjuvant treatment.</p><h3>Methods</h3><p>Eligible patients were randomly assigned in a 1:1 ratio to either receive maintenance low-dose capecitabine therapy or undergo observation within one month of completing standard adjuvant treatment. Patients allocated to the intervention arm received oral capecitabine at a dose of 650 mg/m² twice daily, administered continuously for 12 months in a metronomic schedule.</p><h3>Results</h3><p>Seventy-five patients were randomized to maintenance capecitabine (<i>n</i> = 39) or observation (<i>n</i> = 36), with comparable baseline characteristics. Regarding the primary endpoint, maintenance low-dose capecitabine was generally well tolerated. The most frequent adverse event was hand–foot syndrome, occurring in 28.2% of patients, with one grade 3 case (2.6%). Other toxicities, including gastrointestinal upset, neutropenia, and thrombocytopenia, were infrequent.</p><p>After a median follow-up of 32 months, 24 disease-free survival (DFS) events were recorded: six in the capecitabine group (two local recurrences and four distant metastases) and 18 in the observation group (three local recurrences and 15 distant metastases). Kaplan–Meier analysis demonstrated a significantly lower event rate in the capecitabine arm (<i>p</i> = 0.003). Survival analysis demonstrated a hazard ratio of 5.3 (95% CI: 1.04–26.8). The cumulative metastasis rate was 15.4% in the capecitabine group compared with 50% in the control group (<i>p</i> = 0.003). Estimated 32-month overall survival (OS) rates were 94.9% and 77.8%, respectively (<i>p</i> = 0.04).</p><h3>Conclusions</h3><p>One year of maintenance low-dose capecitabine after standard adjuvant treatment was well tolerated, with hand–foot syndrome identified as the most frequent adverse event. While the trial was powered for safety, exploratory analyses also showed significant improvements in disease-free and overall survival along with reduced metastasis rates, in early-stage triple-negative breast cancer, warranting confirmation in larger, dedicated efficacy trials.</p><p>Trial registration: ClinicalTrials.gov, NCT07143097. Registered 19 August 2025—Retrospectively registered, https://clinicaltrials.gov/study/NCT07143097?tab=history.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00964-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737659","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":"The double-edged sword of meat preservation: a review of nitrosamine genotoxicity, exposure in the egyptian market, and future alternatives","authors":"Kareem M. Arafa,&nbsp;Noran F. Shoman,&nbsp;Alaa A. Hassan,&nbsp;Hussein R. Abdelnaby,&nbsp;Mostafa Abed Tawfiek,&nbsp;Sarah A. Khater","doi":"10.1186/s43094-026-00981-0","DOIUrl":"10.1186/s43094-026-00981-0","url":null,"abstract":"<div><p>Global population growth and the rising demand for food have necessitated effective preservation techniques to prevent spoilage and ensure food security. Nitrite and nitrate salts are the most common methods used for meat preservation. However, their use presents a significant public health dilemma: under acidic conditions, these salts can be converted into the procarcinogenic, nitrosamines (NAs). The International Agency for Research on Cancer (IARC) classifies processed meat as carcinogenic to humans (Group 1). Many studies link their consumption to colorectal cancer (CRC), the third most common cancer worldwide and the eighth in Egypt, with an estimated incidence in Egypt of approximately 9.8 per 100,000 cases. The levels of NAs in processed meat differ widely, from being below detectable levels (&lt; 1 μg/kg) in certain foods to thousands of μg/kg in others. Most existing studies on nitrosamine exposure rely on the Western market, creating a critical knowledge gap in the Egyptian market. This review bridges the gap by analysing residue levels especially in the Egyptian market and integrating these findings with a review of molecular toxicity mechanisms. Additionally, it provides a risk assessment that includes cumulative exposure from non-dietary sources and evaluates sustainable preservation alternatives.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00981-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737608","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":"Assessing the genetic contribution of certain GAS6/AXL variants to diabetic kidney disease susceptibility in Egyptian patients: a case–control observational study","authors":"Tarek Kamal Motawi,&nbsp;Dina Sabry,&nbsp;Nancy Mamdouh Ahmed,&nbsp;Nancy Nabil Shahin","doi":"10.1186/s43094-026-00975-y","DOIUrl":"10.1186/s43094-026-00975-y","url":null,"abstract":"<div><h3>Background</h3><p>Diabetic kidney disease (DKD) denotes the structural and functional alterations in renal tissues occurring as a diabetic complication. Growth arrest-specific 6 (GAS6) and its receptor AXL have been identified as biological markers linked to DKD. Single nucleotide polymorphisms (SNPs) serve as valuable markers for assessing polygenic diseases like DKD. This study investigated the association of GAS6 rs8191974, rs9577873, AXL rs2304232, and rs4802113 with DKD in Egyptians.</p><h3>Methods</h3><p>SNP selection was based on previous literature, and potential functional impact according to Ensembl Variant Effect Predictor. The SNPs were genotyped in 70 type 2 diabetic patients with normal kidney functions and diabetic duration &gt; 5 years as the DM group, 70 type 2 diabetic patients showing microalbuminuria (30–300 mg/day) as the DKD group, and 60 apparently healthy controls, using TaqMan genotyping assays. Glycosylated hemoglobin, plasma creatinine and fasting plasma glucose levels were determined spectrophotometrically. Urinary albumin, plasma GAS6 and AXL levels were assayed using ELISA kits.</p><h3>Results</h3><p>Genotyping of the SNPs in cases and controls fitted the Hardy–Weinberg equilibrium (<i>p</i> &gt; 0.05). The genotypic frequencies as compared between cases and controls for rs8191974 (<i>p</i> = 0.609, χ² = 2.703), rs9577873 (<i>p</i> = 0.916, χ² = 4.611), rs2304232 (<i>p</i> = 0.215, χ² = 5.799) and rs4802113 (<i>p</i> = 0.742, χ² = 6.828) revealed no statistically significant differences. Genotypic variation in the analyzed SNPs within each group did not influence plasma GAS6 or AXL levels. No significant associations were noticed between studied parameters and SNP alleles.</p><h3>Conclusion</h3><p>No significant association was found between GAS6 rs8191974, GAS6 rs9577873, AXL rs2304232, or AXL rs4802113 and the development of type 2 diabetes or DKD in Egyptians. To date, this is the first genetic study assessing GAS6/AXL gene variants association with DKD in the Egyptian population.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00975-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147737658","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 vitro efficacy of ceftazidime/avibactam and cefiderocol against multidrug-resistant Gram-negative uropathogens: insights into β-lactamase-mediated resistance in clinical isolates","authors":"Mohamed A. Ibrahim,&nbsp;Hisham A. Abbas,&nbsp;Ghada H. Shaker,&nbsp;Ahmed M. El-Baz","doi":"10.1186/s43094-026-00946-3","DOIUrl":"10.1186/s43094-026-00946-3","url":null,"abstract":"<div><h3>Background</h3><p>Urinary tract infections (UTIs) are among the most common bacterial infections in hospitalized patients, frequently caused by Gram-negative bacteria such as <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Proteus mirabilis</i>, and <i>Pseudomonas aeruginosa</i>. The increasing prevalence of multidrug-resistant (MDR) isolates, mainly those producing β-lactamases, presents a major therapeutic challenge. This study investigates the in vitro efficacy of ceftazidime–avibactam (CZA) and cefiderocol against MDR Gram-negative uropathogens.</p><h3>Methods</h3><p>A total of 110 Gram-negative uropathogens were included in this study. The isolates were re-identified using standard biochemical tests, and antimicrobial susceptibility was assessed via the disk diffusion method. Phenotypic and genotypic methods were performed to detect β-lactamase production in selected MDR isolates.</p><h3>Results</h3><p>Among the retrieved isolates, 89 (80.9%) were MDR. The highest MDR rates were observed in <i>P. mirabilis</i> (100%) and <i>P. aeruginosa</i> (91%), followed by <i>K. pneumoniae</i> (90%) and <i>E. coli</i> (66%). Most isolates showed high resistance to β-lactams, fluoroquinolones, and aminoglycosides. CZA showed variable activity, with the highest susceptibility in <i>P. mirabilis</i> (100%) and <i>E. coli</i> (68.1%), while resistance was significant in <i>K. pneumoniae</i> (83.3%) and <i>P. aeruginosa</i> (77.3%). Notably, cefiderocol exhibited strong in vitro activity against CZA- and carbapenem-resistant isolates, based on disk diffusion testing. Molecular analysis revealed high rates of ESBL and carbapenemase genes, particularly <i>blaNDM-1</i>, <i>blaVIM-1</i>, and <i>blaOXA-48</i>, among CZA-resistant isolates.</p><h3>Conclusion</h3><p>These findings highlight the alarming resistance to CZA among carbapenemase and MBL producers, emphasizing the urgent need for continuous surveillance. Conversely, cefiderocol demonstrated enhanced in vitro efficacy against highly resistant isolates.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"12 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1186/s43094-026-00946-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147642765","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}