DARU Journal of Pharmaceutical Sciences最新文献

{"title":"Characterization of acquired capecitabine resistance in MKN-45 gastric cancer cells reveals preserved apoptotic sensitivity.","authors":"Habibeh Sadat Mohseni, Shohreh Tavajohi, Abbas Kebriaeezadeh, Mohammad Hossein Ghahremani, Seyed Nasser Ostad","doi":"10.1007/s40199-026-00653-7","DOIUrl":"https://doi.org/10.1007/s40199-026-00653-7","url":null,"abstract":"<p><strong>Background: </strong>Capecitabine (Cap) is widely used in the treatment of advanced gastric cancer; however, the emergence of acquired resistance remains a major obstacle to its long-term efficacy. Although several gastric cancer models resistant to 5-fluorouracil (5-FU) have been reported, experimentally characterized gastric cancer models of Cap resistance remain limited.</p><p><strong>Objectives: </strong>This study aimed to establish and characterize a Cap-resistant MKN-45 gastric cancer cell model. with a focus on phenotypic alterations associated with acquired drug adaptation.</p><p><strong>Methods: </strong>A Cap-resistant MKN-45 subline (MKN-45/R-CapIC₆₀) was generated through exposure of parental MKN-45 cells to gradually increasing concentrations of Cap. Cell viability was evaluated using the MTT assay. Morphological alterations were examined by phase-contrast microscopy, while apoptosis, cell-cycle distribution, and surface c-Met expression were analyzed by flow cytometry.</p><p><strong>Results: </strong>The established resistant subline exhibited a moderate level of Cap resistance, with an approximately 2- to 4-fold increase in the resistance index (RI) compared with the parental cells. Resistant cells showed morphological remodeling characterized by an elongated spindle-like morphology and increased adherence to the culture surface compared with parental cells. Surface c-Met expression was altered in resistant cells and further decreased following Cap exposure. Despite the acquisition of a resistance phenotype, Cap exposure retained biological activity in resistant cells by reducing proliferation, altering cell-cycle distribution through impaired G1/S transition, and increasing late apoptotic/necrotic populations.</p><p><strong>Conclusions: </strong>The findings suggest that the established Cap-resistant gastric cancer cell model retains responsiveness to Cap exposure despite the acquisition of a resistance phenotype. This model may provide a useful platform for investigating early phenotypic adaptations associated with the development of drug resistance in gastric cancer.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient knowledge and medication safety in chronic warfarin therapy: the roles of adherence, diet, and drug-drug interactions.","authors":"Ahmet Çakır, Melisa Sultan Tekşahin, Hasan Memiş, Mehmet Cansel","doi":"10.1007/s40199-026-00649-3","DOIUrl":"10.1007/s40199-026-00649-3","url":null,"abstract":"<p><strong>Background: </strong>Anticoagulant knowledge, medication adherence, time in therapeutic range (TTR), and potential drug-drug interactions (pDDIs) are poorly understood, but they can increase the risk of thromboembolic events, major bleeding, and mortality.</p><p><strong>Objectives: </strong>This study examined the relationship between oral anticoagulation knowledge and adherence in adults on long-term warfarin therapy, and their associations with TTR, clinical and demographic factors, bleeding risk, and pDDIs.</p><p><strong>Methods: </strong>This cross-sectional study included adults on chronic warfarin therapy at a university-affiliated cardiology clinic. Turkish versions of the validated Oral Anticoagulation Knowledge (OAK) and Anticoagulant Therapy Adherence Scale (ATAS) assessed oral anticoagulation knowledge and adherence. Clinical, laboratory, and treatment data were obtained from health records, and lifestyle information via patient interviews. pDDIs were evaluated using UpToDate^® and Micromedex^®. TTR was calculated using the Roosendaal method, and bleeding risk was assessed using the ATRIA score.</p><p><strong>Results: </strong>The study included 126 adults on warfarin therapy, with a median TTR of 31.9% and 76% of patients below 60%. Patients exhibited moderate oral anticoagulant knowledge and relatively high self-reported adherence scores. A weak positive correlation (ρ = 0.24, p = 0.006) was detected between OAK and ATAS scores, while a negative correlation (ρ=-0.179, p = 0.045) was found between OAK and concurrent medications excluding warfarin. Education and employment status were associated with OAK scores, while the frequency of vitamin K-rich food consumption was associated with ATAS scores. Age and renal impairment were associated with an increased number of concurrent medications excluding warfarin and pDDIs identified by both UpToDate^® and Micromedex^® (p < 0.05). ATAS subscale-1 scores differed significantly by education level (p = 0.033), with the highest median observed in illiterate patients and lower scores in university graduates. Higher frequency of vitamin K-rich food consumption was significantly associated with lower ATAS subscale-2 scores (p < 0.001), indicating poorer dietary adherence.</p><p><strong>Conclusion: </strong>Anticoagulation knowledge was weakly associated with adherence to warfarin therapy but not with anticoagulation control. Dietary behaviours, polypharmacy, and pDDIs may influence anticoagulation outcomes, highlighting the need for multifaceted management strategies.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trehalose's untapped mechanisms in alzheimer's: gut-brain-autophagy signalling beyond the usual targets.","authors":"Sathish Kumar Gunasekaran, Harshith Kariappa C K, Mirunalini Gobinath, Parikshit Roychowdhury, Manjula S N","doi":"10.1007/s40199-026-00647-5","DOIUrl":"10.1007/s40199-026-00647-5","url":null,"abstract":"<p><strong>Background: </strong>Trehalose is a promising therapeutic candidate for Alzheimer's disease (AD) that is known to induce autophagy and facilitate misfolded proteins clearance such as amyloid-β and hyperphosphorylated tau. Despite there is emerging evidence that trehalose has a wider range of molecular mechanisms and thus has a greater neuroprotective profile.</p><p><strong>Objective: </strong>To summarize the emerging molecular mechanisms underlying the neuroprotective effects of trehalose beyond classical autophagy and discuss its therapeutic potential in AD.</p><p><strong>Methods: </strong>Published evidence from preclinical studies including in-vitro and in-vivo models, along with hypothetical and emerging findings from early clinical investigations was reviewed to evaluate the molecular mechanisms, therapeutic effects, and translational challenges associated with trehalose in AD.</p><p><strong>Results: </strong>In addition to classical autophagy signalling, recent studies have demonstrated that autophagy can also regulate the stability of neuronal membrane microdomains, prevent lipid bilayers disruption by amyloid proteins, and regulate stress granules dynamics that affect the function of RNA-binding proteins. Other discoveries indicate that interactions with nutrient-sensing pathways and glucose transporter systems that simulate metabolic stress, which may activate protective mechanisms separate from the inhibition of mTOR. Trehalose could also involve in lysosomal-autophagosome fusion and modulate the microglia and astrocytes activation, suggesting an important immunometabolic function. Trehalose often connects to the gut-brain axis and show their effect in gut microbiota composition, microbial metabolite signalling and gut barrier function. These effects can influence systemic inflammation, availability of short-chain fatty acids, bile acid profiles and vagus-mediated gut-to-brain communication, all of which can influence neuroinflammation networks in AD.</p><p><strong>Conclusion: </strong>Although promising results have been reported, primarily from preclinical studies, with early human investigations now beginning to emerge, opportunities remain to address, such as poor oral bioavailability, penetration into the brain and long-term safety in elderly patients. Mechanistic dissection in multi-omics approaches, microbiome-stratified models and early-phase clinical testing are the areas that need to be targeted in future research. A broader understanding of the mechanisms of action of trehalose provides a good chance to reimagine its therapeutic implications and develop novel approaches to AD.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antifungal activities and toxicity studies of water-soluble non-steroidal analgesic salts.","authors":"Julian Gonzalo Arrieta, Natali Ivana Carrizo, Franco Augusto Aguilar, Guillermo Antonio Garcia Pitalluga, Diego Alejandro Sampietro, Melina Araceli Sgariglia, José Rodolfo Soberón","doi":"10.1007/s40199-026-00645-7","DOIUrl":"10.1007/s40199-026-00645-7","url":null,"abstract":"<p><strong>Background: </strong>The emergence of antifungal resistance among Candida albicans strains poses a growing clinical challenge, underscoring the urgent need for alternative therapeutic strategies. Drug repositioning of non-steroidal anti-inflammatory drugs (NSAIDs) has attracted attention due to their reported antimicrobial properties and well-established safety profiles.</p><p><strong>Objectives: </strong>This study aimed to synthesize and characterize water-soluble sodium salts of ibuprofen (IBU-Na), ketoprofen (KET-Na), and indomethacin (IM-Na), and to evaluate their antifungal activity and toxicity profiles, individually and in combination with fluconazole (FLU), against C. albicans strains.</p><p><strong>Methods: </strong>NSAID sodium salts were synthesized and characterized, and their antifungal activity, synergistic interactions with FLU, and toxicity profiles were evaluated against FLU-susceptible and -resistant C. albicans strains.</p><p><strong>Results: </strong>IBU-Na and KET-Na exhibited inhibitory and fungicidal activities against both FLU-susceptible and -resistant C. albicans strains, whereas IM-Na was inactive. Combination assays revealed strong synergistic interactions with FLU (FICI = 0.008-0.009), resulting in marked reductions in fungal viability. Neither hemolytic activity nor genotoxic effects were detected at the tested concentrations.</p><p><strong>Conclusions: </strong>Water-soluble NSAID salts, particularly IBU-Na, demonstrate potent synergistic antifungal activity with FLU and favorable safety profiles, supporting their potential as candidates for antifungal drug repurposing. These findings emphasize the importance of reassessing sodium salt derivatives rather than assuming equivalence with their acidic precursors.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloin attenuates high-glucose-induced oxidative and inflammatory damage in renal cells via AMPK/Nrf2 signaling.","authors":"Huang Guangde, Fang Yanan","doi":"10.1007/s40199-026-00650-w","DOIUrl":"10.1007/s40199-026-00650-w","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, with proximal tubular injury and oxidative stress playing pivotal roles in its progression. The AMPK-Nrf2 signaling axis is a key regulator of antioxidant defense, but its modulation by Aloin in DN-relevant renal models remains insufficiently characterized. Aloin, a natural anthraquinone glycoside from Aloe species, exhibits antioxidant, anti-inflammatory, and anti-fibrotic properties in non-renal systems. This study investigated whether Aloin protects renal cells from high-glucose-induced injury and whether AMPK and Nrf2 contribute to these protective responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Human renal proximal tubular epithelial cells (HK-2) and human renal glomerular endothelial cells (HRGECs) were exposed to high glucose (HG, 30 mM) for 48 h with or without Aloin (25 or 50 µM). Functional assays included CCK-8 cell viability, colony formation, and wound healing migration analysis. mRNA expression of oxidative stress-related, inflammatory, fibrotic, and phenotype-associated markers, including VIM and CDH1, was quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). siRNA-mediated knockdown of PRKAA1 (AMPK) or NFE2L2 (Nrf2) was performed to assess mechanistic involvement, with gene silencing confirmed by RT-qPCR and Western blotting. For exploratory in vivo validation, male db/db mice received oral Aloin at 25 mg/kg/day for 8 weeks, while age-matched db/m and db/db mice received vehicle (n = 6 per group).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HG exposure reduced proliferation and clonogenic capacity while increasing wound closure under serum-free conditions in both HK-2 cells and HRGECs, accompanied by upregulation of TNF, CCL2, TGFB1, COL1A1, and VIM, and downregulation of NFE2L2, SOD1, PRKAA1, and CDH1. Aloin treatment dose-dependently restored proliferation, reduced migration, and normalized gene expression patterns, with 50 µM producing near-complete reversal toward normal glucose controls. PRKAA1 knockdown in HK-2 cells and NFE2L2 knockdown in HRGECs substantially attenuated Aloin-associated protective responses, supporting the functional involvement of AMPK and Nrf2 in these cell-specific effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Aloin attenuated high-glucose-induced injury in cultured renal tubular epithelial and glomerular endothelial cells, with loss-of-function experiments supporting the involvement of AMPK and Nrf2 in these responses. Exploratory validation in db/db mice further showed reductions in albuminuria, serum creatinine, and mesangial matrix expansion, accompanied by restoration of renal AMPK-Nrf2 signaling. However, the 25 and 50 µM concentrations used in vitro cannot be directly equated with the 25 mg/kg/day oral dose used in mice, and plasma exposure, renal tissue concentrations, pharmacokinetics, and systemic safety were not determined. Additional pharmacokinetic, dose-ranging, and toxicol","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nyctanthes arbor-tristis attenuates hyperglycemia: an integrated experimental and computational investigation.","authors":"Brij Raj Singh, Jagat Pal Yadav, Ashish R Dwivedi, Ankit Kumar Singh, Vikas Kumar, Habibullah Khalilullah, Prateek Pathak, Amita Verma","doi":"10.1007/s40199-026-00646-6","DOIUrl":"10.1007/s40199-026-00646-6","url":null,"abstract":"<p><p>Nyctanthes arbor-tristis Linn. (Oleaceae) is traditionally used for treating metabolic and inflammatory conditions. This investigation aimed to evaluate the antidiabetic potential of the ethanolic leaf extract of N. arbor-tristis through integrated phytochemical, in vitro, in vivo, and in silico approaches. LC-MS analysis revealed 24 bioactive compounds, including flavonoids, phenolic acids, terpenoids, and cucurbitacins. Antioxidant assays demonstrated significant free radical scavenging and reducing activities (DPPH IC₅₀ = 66.56 µg/mL, ABTS = 19.31 µg/mL, FRAP = 3.68 µg/mL), comparable to ascorbic acid. The extract also showed potent inhibition of carbohydrate-hydrolyzing enzymes (α-amylase IC₅₀ = 49.09 µg/mL; α-glucosidase IC₅₀ = 45.52 µg/mL) and enhanced glucose uptake in L6 skeletal muscle cells, reaching 617.45 µg/mL at 500 µg/mL concentration.In vivo, STZ-induced diabetic rats treated with the extract (100-300 mg/kg) for 21 days showed significant reductions in fasting blood glucose, improved oral glucose tolerance, weight restoration, and favorable modulation of lipid profiles. The extract also enhanced antioxidant enzyme activities (CAT, SOD, GPx) and reduced lipid peroxidation (MDA), suggesting oxidative stress attenuation. Molecular docking identified key phytoconstituents with high binding affinity for GLUT1 and α-glucosidase, supporting a multi-targeted mechanism.Collectively, the findings demonstrate the antidiabetic potential of N. arbor-tristis in preclinical experimental models and suggest that enzymatic inhibition, antioxidant effects, and modulation of glucose metabolism may contribute to its biological activity. However, the study is limited to preclinical investigations, and further mechanistic, toxicological, and clinical studies are required to validate these findings.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of herbal formula based on rosa damascena on functional bloating severity in older adults: a pilot double-blind randomized controlled trial.","authors":"Mokhtar Hedayati, Seyed Hamdollah Mosavat, Majid Saeedi, Mahmood Moosazadeh, Arash Kazemi Veisari, Assie Jokar","doi":"10.1007/s40199-026-00643-9","DOIUrl":"10.1007/s40199-026-00643-9","url":null,"abstract":"<p><strong>Introduction: </strong>This study explores the efficacy and tolerability of an herbal formula, based on Rosa damascena (an oral syrup) carminative properties, rooted in Traditional Persian Medicine in the management of functional bloating. It aims to evaluate its efficacy in reducing bloating severity among older adults, integrating traditional and modern therapeutic approaches.</p><p><strong>Methods: </strong>In this double-blind, randomized controlled trial, 72 participants aged 60 years and older with functional bloating were randomly assigned to receive either herbal syrup or a placebo, twice daily for 4 weeks. The primary outcome was bloating severity score, measured using the Gastrointestinal Symptom Rating Scale (GSRS). .(1). Acid reflux severity, constipation severity and defecation frequency were secondary outcome measures. Both outcomes were assessed at baseline and weekly during the study period (days 7, 14, 21, and 28) through in-person and telephone interviews. Data analysis was conducted using SPSS version 26.</p><p><strong>Results: </strong>60 participants completed it (32 in the herbal group and 28 in the placebo group). At baseline, there was no significant difference in the bloating severity between the intervention and placebo groups (P = 0.722). After one week, the intervention group showed a significantly lower bloating severity compared to the placebo group (P = 0.002), and this difference became even more pronounced by the end of the fourth week (P < 0.001). Furthermore, the Defecation Frequency Rate (DFR) significantly improved in the intervention group compared with the placebo group after the study (P < 0.001).</p><p><strong>Conclusion: </strong>The herbal formula appears to be an effective and well-tolerated therapeutic option for managing functional bloating in older adults. Significant improvements in bloating and defecation were observed throughout the study.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory effects of glycyrrhizin and glucomannan on cytokine gene expression in human PBMCs: implications for vaccine adjuvant development.","authors":"Mohammad-Reza Sanaye-Pasand, Hedieh Sadat Shamsnia, Ahmad Reza Shahverdi, Mohammad- Reza Delnavazi, Mohammad Hossein Yazdi","doi":"10.1007/s40199-026-00640-y","DOIUrl":"https://doi.org/10.1007/s40199-026-00640-y","url":null,"abstract":"<p><strong>Background: </strong>Vaccine adjuvants enhance immune responses to weak antigens. Natural compounds such as glycyrrhizin and glucomannan show immunomodulatory potential, but their combined effects on human cytokine expression as an adjuvant remain unclear.</p><p><strong>Objective: </strong>To evaluate the immunomodulatory effects of glucomannan (GA) from Amorphophallus konjac and glycyrrhizin (GL) from Glycyrrhiza glabra on cytokine gene expression in human peripheral blood mononuclear cells (PBMCs), assessing their potential to promote Th1 polarization as candidate vaccine adjuvants.</p><p><strong>Methods: </strong>PBMCs isolated from ten healthy donors were treated with GA and GL at 25 and 50 µg/mL, either individually or in combination. Cell viability was assessed using the MTT assay. Gene expression levels of pro-inflammatory cytokines (IL-6, TNF-α), the Th1 cytokine (IFN-γ), and Th2/regulatory cytokines (IL-10, TGF-β) were quantified using RT-qPCR.</p><p><strong>Results: </strong>GA and GL significantly increased IL-6, TNF-α, and IFN-γ expression in a dose-dependent manner (p < 0.05 to p < 0.001), while significantly reducing IL-10 and TGF-β expression compared with the control group (p < 0.05 to p < 0.001). The combined treatment produced the strongest immunomodulatory response, characterized by enhanced expression of pro-inflammatory and Th1-associated cytokines and greater suppression of Th2/regulatory cytokines relative to individual treatments (p < 0.001). The MTT assay identified 25 and 50 µg/mL as safe and effective GA concentrations for subsequent experiments, based on cell proliferation and cytotoxicity assessments.</p><p><strong>Conclusion: </strong>In human PBMCs, GA and GL promote a Th1-biased cytokine response at the mRNA expression level under in vitro conditions, suggesting their implications for vaccine adjuvant development. However, these results are limited to in vitro gene expression data and have not been validated at the protein level, a gap that warrants further investigation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plozasiran: a small interfering RNA therapy for hypertriglyceridemia and familial chylomicronemia syndrome.","authors":"Jennifer Rodriguez-Montes, Genevieve Hale, Tina Benny","doi":"10.1007/s40199-026-00638-6","DOIUrl":"10.1007/s40199-026-00638-6","url":null,"abstract":"<p><p>Plozasiran (Redemplo^®) is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides. It degrades ApoC-III mRNA and results in reduced levels of hepatic and serum ApoC-III protein, which leads to an increased clearance of serum triglycerides. In the phase 3 PALISADE trial, plozasiran 25 mg reduced fasting triglyceride levels by approximately 80% at 10 months in patients with familial chylomicronemia syndrome (FCS) and was associated with a lower incidence of pancreatitis compared with placebo. This provides supportive, yet not definitive, evidence for pancreatitis prevention as the PALISADE trial was powered to investigate triglyceride lowering. Across completed clinical studies, plozasiran demonstrated a generally favorable safety profile, with a low incidence of thrombocytopenia and adverse events primarily limited to abdominal pain, nasopharyngitis, headache, and nausea. Hyperglycemia was observed in some patients with preexisting diabetes or prediabetes at baseline. Ongoing phase 3 trials (SHASTA-3, SHASTA-4, SHASTA-5, SHASTA-10, MUIR-3 and CAPITAN) are further evaluating the efficacy and safety of plozasiran in broader populations with hypertriglyceridemia, including its potential role in reducing cardiovascular risk and preventing pancreatitis. Compared with earlier ApoC-III-targeted antisense oligonucleotides, plozasiran offers the advantages of less frequent dosing, sustained pharmacodynamic effects, and potentially a more favorable tolerability profile based on indirect evidence, positioning it as a promising therapeutic option for patients with FCS and other severe hypertriglyceridemia disorders inadequately managed with existing therapies.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological effects of statins in systemic sclerosis: a systematic review and meta-analysis of 323 patients.","authors":"Mostafa A Khalifa, Hamzah M Alghzawi, Shehabeldin S Anan, Ahmad Al Rifai, Ayah A Anwar, Hayder Ali Raheem Al-Saedi, Eman Awady, Islam Masood, Mohamed Elsayed Badr, Mohamed Ismail, Obada Muayaid, Omar M Ahmed, Osama Bdarnh, Sarah Alkhatib, Fares Elnagar, Yasser Hegazi, Mohammad Jebril","doi":"10.1007/s40199-026-00639-5","DOIUrl":"10.1007/s40199-026-00639-5","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic sclerosis (SSc) is driven by persistent inflammation and microvascular damage. Statins are hypothesized to offer vasculoprotective effects beyond lipid-lowering. We systematically evaluated the efficacy and safety of statins in SSc across biochemical, vascular, and patient-centred outcomes.</p><p><strong>Methods: </strong>Following PRISMA guidelines, a systematic search of four electronic databases was conducted up to August 2025. Ten studies involving 323 patients were included. Pooled estimates were calculated using a random-effects model. Heterogeneity and sensitivity analyses were performed, and study quality was assessed using standardized appraisal tools.</p><p><strong>Results: </strong>Statin therapy was associated with significant biochemical improvements. Compared with baseline or placebo, CRP decreased by an average of 0.70 mg/L, IL-6 by 5.56 pg/mL, and fibrinogen by 40 mg/dL. Endothelial markers showed similar reductions: 0.85 pg/mL for ET-1, 23.17 IU/dL for vWF, and 25 ng/mL for ICAM-1. Total cholesterol and LDL decreased by mean differences of 0.93 mmol/L and 0.76 mmol/L, respectively, while HDL showed no meaningful change.</p><p><strong>Conclusion: </strong>Statins improve inflammatory and endothelial pathways in systemic sclerosis, but these findings should be interpreted cautiously, as clinical benefits remain minimal. Randomized trials are required to further study statins' therapeutic role beyond biochemical modulation.</p>","PeriodicalId":10888,"journal":{"name":"DARU Journal of Pharmaceutical Sciences","volume":"34 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}