Future Science OAPub Date : 2026-12-01Epub Date: 2026-01-12DOI: 10.1080/20565623.2025.2580892
Mai O Kadry, Rehab M Abdel-Megeed
{"title":"Autophagy targeted nano-medicine in norphytane atrophic arthritis model: Beclin1/XBP/PTEN/STAT-3A genetic profile.","authors":"Mai O Kadry, Rehab M Abdel-Megeed","doi":"10.1080/20565623.2025.2580892","DOIUrl":"10.1080/20565623.2025.2580892","url":null,"abstract":"<p><strong>Background and objectives: </strong>Targeting macro-autophagy (MAut) through Nano-medicine can be more prospective than traditional medicine subjected to resistance in atrophic arthritis (RA). MAut is a degenerative process that restores healthy chondrocytes it plays a vital role in RA onset and cell homeostasis this opened Novel Avenue in targeting RA via liposomal drug delivery system. The insufficient response to existing therapies or systemic toxicity and poor bioavailability, are quiet unsettled problems lying across the full retardation of RA treatment. Various Nano-carriers with sustained drug release, improved physicochemical properties, and active targeting were designed to promote the drug delivery efficiency.</p><p><strong>Methods: </strong>Single subcutaneous dose of Norphytane (200 μL) induced Atrophic arthritis in rat model then rats were treated with Liposomal loaded-Isethione or Isethione.</p><p><strong>Results: </strong>Liposomal-Isethione ameliorated autophagy biomarkers including <i>Beclin-1</i>, <i>P62</i>, and X-box binding protein-1 (<i>XBP-1</i>), cell survival, and oncogenic biomarkers including Signal transducer and activator of transcription (<i>STAT-3A</i>), Phosphoinisitol kinase-3 (<i>PI3K</i>), AKT Serine/Threonine Kinase-1 (<i>AKT</i>), and Phosphatase and tensin homolog (<i>PTEN)</i> post elevation via Norphytane. Moreover, rheumatoid factor biomarkers including Cartilage oligomeric matrix protein (<i>COMP</i>), matrix metalloproteinase (<i>MMP-9</i>), tumor necrosis factor (TNF-α).</p><p><strong>Conclusion: </strong>Liposomal-Isethione significantly targeted MAut signaling pathways, including <i>Beclin-1/XBP/COMP/STAT-3A/PI3K/AKT/PTEN via</i> increased bioavailability and targeting inflamed tissues, thus decreased drug resistance.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2580892"},"PeriodicalIF":2.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959172","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2025-12-24DOI: 10.1080/20565623.2025.2581460
Mahshad Mir, Rezvaneh Mohebbi, Ghader Mohammadnezhad, Seyed Ahmad Raeissadat, Alireza Parhizgar, Hadi Esmaily
{"title":"Intra-articular injection of high versus low molecular weight hyaluronic acid in adhesive capsulitis; randomized trial.","authors":"Mahshad Mir, Rezvaneh Mohebbi, Ghader Mohammadnezhad, Seyed Ahmad Raeissadat, Alireza Parhizgar, Hadi Esmaily","doi":"10.1080/20565623.2025.2581460","DOIUrl":"10.1080/20565623.2025.2581460","url":null,"abstract":"<p><strong>Background: </strong>Adhesive capsulitis (AC) is a chronic inflammatory condition with limited range of motion (ROM) in the glenohumeral joint. The main goals in managing AC are pain reduction and returning joint function. Intra-articular hyaluronic acid (HA) has been considered a safe modality in AC. This study compared the effectiveness of intra-articular injection of low molecular weight (LMW) with high molecular weight (HMW) HA in patients with AC.</p><p><strong>Methods: </strong>Fifty-six patients with AC were randomized in this triple-blinded clinical trial. All underwent standard physical therapy. The outcomes were visual analog scale (VAS), Oxford shoulder score (OSS), active ROM, and patient satisfaction at 4, 12, and 24 weeks.</p><p><strong>Results: </strong>No significant differences were detected in between-group variables at baseline. Both groups showed marked improvement in VAS, OSS, and ROM over time. At four weeks LMW-HA group had lower pain (<i>P</i> = 0.049). Conversely, the trend of VAS at 12-week and 24-week endpoints favors HMW-HA (Baseline to endpoint: -5.48 ± 1.68 and -3.91 ± 1.31 reduction in VAS as the primary outcome, <i>P</i> < 0.001). Satisfaction had significantly improved in both groups.</p><p><strong>Conclusion: </strong>HMW-HA was associated with greater pain reduction and functional improvement compared with LMW-HA.</p><p><strong>Trial registration: </strong>The trial protocol was registered at the Iranian Registry of Clinical Trials (IRCT), a WHO Primary Register setup (registration No: IRCT20170608034390N4; First registration date: 01/01/2020).</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2581460"},"PeriodicalIF":2.1,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818919","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-07-15DOI: 10.1080/20565623.2026.2702980
Yue Liu, Zhiyuan Wang, Weixing Liu, Pei Li, Jia Chen, Zhi Shi, Jin Ye
{"title":"USP14 promotes head and neck squamous cell carcinoma progression via deubiquitinating and stabilizing CFL2.","authors":"Yue Liu, Zhiyuan Wang, Weixing Liu, Pei Li, Jia Chen, Zhi Shi, Jin Ye","doi":"10.1080/20565623.2026.2702980","DOIUrl":"10.1080/20565623.2026.2702980","url":null,"abstract":"<p><strong>Aim: </strong>To identify novel substrates of USP14 and elucidate the molecular mechanisms by which USP14 promotes head and neck squamous cell carcinoma (HNSCC) progression.</p><p><strong>Materials and methods: </strong>USP14 expression patterns were examined in HNSCC tissues and cell lines. Functional effects were assessed using genetic knockout and overexpression models <i>in vitro</i> and <i>in vivo</i>. USP14-CFL2 interactions were evaluated by co-immunoprecipitation and GST pull-down assays. Deubiquitination activity was measured <i>in vitro</i>. Transcriptomic analysis and bioinformatics were used to identify downstream pathways and clinical relevance.</p><p><strong>Results: </strong>USP14 was significantly overexpressed in HNSCC and correlated with poor prognosis. Genetic knockout of USP14 markedly suppressed HNSCC cell proliferation, migration, and tumor growth, while USP14 overexpression exerted opposite effects. Mechanistically, we identified CFL2 as a novel substrate of USP14; USP14 directly interacted with and deubiquitinated CFL2, thereby enhancing its stability by preventing proteasomal degradation. Clinically, CFL2 was also overexpressed in HNSCC and its elevated levels correlated with reduced overall survival. Functionally, CFL2 overexpression significantly rescued the anti-tumor effects of USP14 knockout, including impaired cell proliferation and migration.</p><p><strong>Conclusion: </strong>In summary, our findings identify a novel USP14-CFL2 regulatory axis and establish USP14 as a critical promoter of HNSCC progression, acting through CFL2 deubiquitination and stabilization.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2702980"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13374754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445568","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-06-24DOI: 10.1080/20565623.2026.2668083
Pellegrino Cerino, Antonio Pizzolante, Carlo Buonerba, Paolo Montuori
{"title":"Serum trace metals across environmental-pressure strata in Campania, Italy (SPES): a population-based cross-sectional biomonitoring study.","authors":"Pellegrino Cerino, Antonio Pizzolante, Carlo Buonerba, Paolo Montuori","doi":"10.1080/20565623.2026.2668083","DOIUrl":"10.1080/20565623.2026.2668083","url":null,"abstract":"<p><strong>Background and objectives: </strong>We characterized fine-scale geographic variation in serum trace metals across Campania (southern Italy).</p><p><strong>Materials and methods: </strong>In 2016-2017, the SPES programme sampled residents aged 20-49 years from municipal registries across Campania. Municipalities were stratified using an environmental-pressure index into three broad impact strata: high-impact, medium-impact and low-impact. For higher spatial resolution, municipalities were also grouped into 21 predefined municipal clusters. We measured 20 serum trace metals by ICP-MS and estimated age- and sex-adjusted geometric mean ratios (GMRs) comparing each stratum or cluster with the study-wide geometric mean.</p><p><strong>Results: </strong>Of 4205 enrolled participants, 4188 were included. Medium-impact areas showed higher mercury (GMR 1.87, 95% CI 1.73-2.02) and antimony (1.95, 1.71-2.23) relative to the cohort average. At the municipal-cluster scale, the Irno Valley clusters around the Fonderie Pisano foundry (Baronissi-Pellezzano and Salerno) had about six-fold higher mercury (GMR 5.71 and 6.10) and about three-fold higher antimony (3.45 and 2.93), whereas the Valle del Sabato cluster showed about ten-fold higher antimony (GMR 10.5) and about seven-fold higher nickel (7.16) and cadmium (7.67).</p><p><strong>Conclusions: </strong>Overall serum metal concentrations were broadly comparable with European general-population ranges, but pronounced small-area heterogeneity indicates localized hotspots that provincial or regional averages can obscure.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2668083"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307901","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":"Continuous spinal anesthesia for TURBT in a morbidly obese patient with EF of 20%: a case report.","authors":"Mustapha Nahle, Mohamad Akhrass, Zakaria Tawbe, Mohamad Ghandour","doi":"10.1080/20565623.2026.2645372","DOIUrl":"10.1080/20565623.2026.2645372","url":null,"abstract":"<p><strong>Background: </strong>Patients with severely reduced left ventricular function pose major anesthetic challenges. General anesthesia may cause cardiac depression and pulmonary decompensation, while single-shot spinal anesthesia can trigger sudden hypotension. Continuous spinal anesthesia (CSA), however, allows gradual dosing and improved hemodynamic stability in such high-risk patients.</p><p><strong>Case presentation: </strong>We report a 133-kg man with atrial fibrillation, left bundle branch block, global hypokinesia, ejection fraction (EF) of 20%, and prior pulmonary tuberculosis with lung congestion, who underwent transurethral resection of a bladder tumor (TURBT) under CSA. Using the epidural loss-of-resistance technique at L4-L5, a catheter was advanced to 12 cm (6 cm intrathecal). Incremental doses of 1 mg isobaric bupivacaine were administered every 15 minutes to a total of 5 mg. Noninvasive blood pressure was monitored every minute. Baseline BP was 154/98 mmHg and remained stable at 135/90 mmHg intraoperatively, with a heart rate of 65-75 bpm. Adequate anesthesia was achieved without vasopressor use, and recovery was uneventful (Table 1).</p><p><strong>Conclusion: </strong>Incremental CSA with isobaric bupivacaine was safely and effectively used in a morbidly obese patient with low EF undergoing TURBT. The technique maintained hemodynamic stability throughout, suggesting CSA as a viable anesthetic option for endoscopic urologic procedures in patients with compromised cardiac function.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2645372"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491131","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":"Association between circadian rhythm-related behaviors and breast cancer: a bidirectional Mendelian randomization study.","authors":"Yan-Yu Hou, Hua-Tao Wu, Wen-Jia Chen, Yang-Zheng Lan, Xin-Ning Yu, Jing Liu","doi":"10.1080/20565623.2026.2631966","DOIUrl":"10.1080/20565623.2026.2631966","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is a major cause of cancer-related morbidity and mortality in women, with its development linked to circadian rhythm disruption. This study employs two-sample bidirectional Mendelian randomization (MR) to explore their causal relationship.</p><p><strong>Materials and methods: </strong>Genome-wide association study (GWAS) from the MRC Integrated Epidemiology Unit (MRC IEU) on circadian rhythm-related behaviors and BC subtypes was used. Causal effects were assessed using multiple MR methods, with IVW as the primary approach. Sensitivity analyses were conducted to ensure result robustness.</p><p><strong>Results: </strong>Increased sleep duration was associated with a higher BC risk (IVW model: OR = 1.33, <i>P</i> < 0.001), while being a morning person (IVW model: OR = 0.76, <i>P</i> = 0.003) and getting up in the morning (IVW model: <i>OR</i> = 0.71, <i>P</i> < 0.001) were protective factors. Similar findings were observed for estrogen receptor-positive (ER+) BC. BC patients were also more likely to experience insomnia (IVW model: OR = 1.01, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Our bidirectional MR study provides genetic evidence for a causal link between genetically predicted circadian rhythm-related behaviors and BC. These findings underscore the role of genetic factors influencing circadian biology in BC etiology and warrant further investigation into the underlying mechanisms.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2631966"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147304709","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-07-01DOI: 10.1080/20565623.2026.2694330
Ahmed Alamer, Taibah AbuTaki, Shareefa Mohammed Alonaizi, Dalal Saadoun Alsaadoun, Mukhtar Alomar
{"title":"Treatment trajectories and patterns following non-medical switching to biosimilar adalimumab in patients with hidradenitis suppurativa: a retrospective observational multicenter study from Saudi Arabia.","authors":"Ahmed Alamer, Taibah AbuTaki, Shareefa Mohammed Alonaizi, Dalal Saadoun Alsaadoun, Mukhtar Alomar","doi":"10.1080/20565623.2026.2694330","DOIUrl":"10.1080/20565623.2026.2694330","url":null,"abstract":"<p><strong>Background: </strong>Adalimumab is the first biologic approved for moderate-to-severe hidradenitis suppurativa (HS). Considering potential cost savings, real-world data evaluating the prescribing patterns following a switch from the originator in HS remain limited.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter observational study (2019-2025) at two hospitals in Saudi Arabia. Adult HS patients who received originator adalimumab for ≥3 months, and then switched to its biosimilar for non-medical reasons for ≥3 months were included. Descriptive statistics summarized baseline characteristics. A Wilcoxon paired test compared treatment durations, and a Sankey diagram illustrated treatment pathways.</p><p><strong>Results: </strong>A total of 40 patients were included (median age: 26 years; 62.5% male; median BMI: 31.6). Most presented with nodules (55.0%), abscesses (47.5%), and sinus tracts (37.5%). Among all treatment actions/pathways, 22.6% represented treatment escalation to an alternative biologic, specifically secukinumab or ustekinumab. Patients who were switched from biosimilar therapy demonstrated more severe disease involvement. Median duration of originator therapy was 6.0 months versus 21.0 months for biosimilar (<i>p</i> = 0.477), with no significant difference in treatment persistence.</p><p><strong>Conclusion: </strong>In this small real-world cohort, treatment escalation after switching to biosimilar adalimumab was observed in a subset of patients with more complex HS features. Larger studies using standardized severity measures are needed to confirm these observations.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2694330"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360241","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-05-15DOI: 10.1080/20565623.2026.2672016
Cameron M Thompson, Michael B Andrews, Douglas G Adler
{"title":"A comprehensive analysis of the adverse drug events of metastatic and unresectable gastrointestinal stromal tumor treatment options: avapritinib, imatinib, regorafenib, ripretinib, and sunitinib safety insights and implications.","authors":"Cameron M Thompson, Michael B Andrews, Douglas G Adler","doi":"10.1080/20565623.2026.2672016","DOIUrl":"10.1080/20565623.2026.2672016","url":null,"abstract":"<p><strong>Background: </strong>Treatments for metastatic, unresectable, or treatment-resistant gastrointestinal stromal tumors (GIST) include avapritinib, imatinib, regorafenib, ripretinib, and sunitinib. The FDA Adverse Event Reporting System (FAERS) database collects medication-related adverse events (AEs).</p><p><strong>Design and methods: </strong>Reports in the FAERS database from each medication's FDA approval to June 30, 2025 were analyzed. Reports containing other medications or indications outside of GIST treatment were excluded.</p><p><strong>Results: </strong>Avapritinib was associated with fatigue (<i>n =</i> 826, 10.2%), nausea/vomiting (<i>n =</i> 574, 7.1%), eye/facial swelling (<i>n =</i> 631, 7.8%), diarrhea <i>n =</i> 361, 4.5%), peripheral edema (<i>n =</i> 231, 2.5%). Imatinib was associated with nausea/vomiting (<i>n =</i> 677, 4.4%), fatigue (<i>n =</i> 549, 3.6%), anemia (<i>n =</i> 404, 2.6%), abdominal pain (<i>n =</i> 400, 2.6%), and rash (<i>n =</i> 340, 2.2%), hemorrhage (317 AEs, 2.1%). Regorafenib was associated with fatigue (<i>n =</i> 104, 8.6%), palmar-plantar erythrodyesthesia syndrome (<i>n =</i> 66, 5.4%), diarrhea (<i>n =</i> 60, 4.9%). Ripretinib was associated with fatigue (<i>n =</i> 534, 8.4%), alopecia (<i>n =</i> 355, 5.6%), nausea/vomiting (<i>n =</i> 273, 4.3%). Sunitinib was associated with fatigue (<i>n =</i> 420, 6.1%%), nausea/vomiting (<i>n =</i> 284, 4.2%), diarrhea (<i>n =</i> 262, 3.8 %), hemorrhage (<i>n =</i> 149, 2.2%).</p><p><strong>Conclusions: </strong>The FAERS database revealed multiorgan AEs associated with five GIST treatment medications. Novel findings include eye/facial and peripheral edema with avapritinib, palmar-plantar erythrodyesthesia syndrome, headache/migraine, and gait abnormalities across all five medications, pancytopenia with imatinib, and hemorrhage with imatinib and sunitinib.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2672016"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941133","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-03-02DOI: 10.1080/20565623.2026.2635722
Fabienne Kerneis, Christopher M Jay, Donald Rao, Jeremy Winchester, Alexander Nemunaitis, Emily Nemunaitis, Ernest Bognar, Gladice Wallraven, Laura Stanbery, Adam Walter, Sep Sarshar, John Nemunaitis
{"title":"Preclinical assessment of GNE<sup>wt</sup>/bi-shRNA-GNE<sup>M743T</sup> lipoplex product development for GNE myopathy.","authors":"Fabienne Kerneis, Christopher M Jay, Donald Rao, Jeremy Winchester, Alexander Nemunaitis, Emily Nemunaitis, Ernest Bognar, Gladice Wallraven, Laura Stanbery, Adam Walter, Sep Sarshar, John Nemunaitis","doi":"10.1080/20565623.2026.2635722","DOIUrl":"10.1080/20565623.2026.2635722","url":null,"abstract":"<p><strong>Aims: </strong>GNE myopathy is a heredity disease of unmet medical need associated with progressive skeletal muscle wasting, atrophy and weakness caused by mutations in the GNE gene. GNE plays a pivotal role in sialic acid production. Sialic acid is a critical part of glycoprotein, ganglioside and glycolipid cell-cell interaction which is necessary for normal skeletal muscle function. Previously we demonstrated safety and efficacy of the GNEwt gene lipoplex in one patient.</p><p><strong>Methods: </strong>We engineered GNE<sup>M743T</sup> and dual function GNEwt/bi-shRNA plasmids to evaluate GNE<sup>M743T</sup> specific knockdown and GNEwt expression. Knockdown efficiency, protein expression, and functional rescue were assessed. A dose range study in mice quantified plasmid delivery and human GNE expression in muscle.</p><p><strong>Results: </strong>We demonstrate effective plasmid function via knockdown of the GNE<sup>M743T</sup> gene mutation and concurrent expression of GNEwt gene in a dose dependent manner. Similar in vitro increase in sialic acid production is shown between prior single function plasmid and GNE<sup>wt</sup>/bi-shRNA-GNEM<sup>743T</sup> dual function plasmid. Moreover, we demonstrate murine <i>in vivo</i> muscle delivery and expression of GNE<sup>wt</sup> mRNA from the GNE<sup>wt</sup>/bi-shRNA-GNE<sup>M743T</sup> plasmid delivered via DOTAP-Cholesterol lipoplex following intravenous injection.</p><p><strong>Conclusion: </strong>These results encourage future studies, potentially leading toward clinical testing of GNE<sup>wt</sup>/bi-shRNA-GNE<sup>M743T</sup> lipoplex for GNE myopathy.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2635722"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325607","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}
Future Science OAPub Date : 2026-12-01Epub Date: 2026-05-08DOI: 10.1080/20565623.2026.2669032
Xizhen Xu, Dong Chen, Nan Luo, Wendi Zhang, Liping Lou
{"title":"Metagenomic next-generation sequencing for pathology-suspected fungal infections at rare anatomical sites: a case series.","authors":"Xizhen Xu, Dong Chen, Nan Luo, Wendi Zhang, Liping Lou","doi":"10.1080/20565623.2026.2669032","DOIUrl":"10.1080/20565623.2026.2669032","url":null,"abstract":"<p><strong>Objective: </strong>Histopathology for suspected fungal infections lacks species-level identification and is prone to morphological mimics. The utility of metagenomic next-generation sequencing (mNGS) at rare anatomical sites is underexplored.</p><p><strong>Methods: </strong>We retrospectively analyzed 10 cases with histopathology suggestive of fungal infection at rare sites (brain, cardiac valve, bone, etc.). All underwent mNGS testing on formalin-fixed paraffin-embedded samples.</p><p><strong>Results: </strong>mNGS detected fungal DNA in 8/10 cases (80%), providing species-level identification (e.g., Cryptococcus, Candida, Fusarium, Rhizopus, Histoplasma). Polymicrobial infections were identified in 70%. mNGS corrected two misdiagnoses: one confirmed neurocysticercosis; another revealed only bacteria in a suspected fungal lesion. Antimicrobial resistance genes (ErmB) were identified in two cases.</p><p><strong>Conclusion: </strong>mNGS enhances diagnostic precision at rare sites by enabling species identification, uncovering polymicrobial infections, and correcting morphological misdiagnoses, supporting targeted therapy.</p>","PeriodicalId":12568,"journal":{"name":"Future Science OA","volume":"12 1","pages":"2669032"},"PeriodicalIF":2.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13166278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836792","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}