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Pharmacists in modern primary care and management of diseases: an evidence-based perspective on emerging technologies. 现代初级保健和疾病管理中的药剂师:新兴技术的循证视角。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-04-22 eCollection Date: 2026-01-01 DOI: 10.34172/bi.33050
Jaleh Barar, Yadollah Omidi
{"title":"Pharmacists in modern primary care and management of diseases: an evidence-based perspective on emerging technologies.","authors":"Jaleh Barar, Yadollah Omidi","doi":"10.34172/bi.33050","DOIUrl":"10.34172/bi.33050","url":null,"abstract":"<p><p>Modern healthcare demands warrant the reconceptualization of pharmaceutical practitioners as primary caregivers capable of addressing contemporary medical challenges. Their specialized knowledge in molecular therapeutics, computational medicine tools, and physiological surveillance technologies uniquely qualifies them to oversee complicated treatment protocols for cutting-edge interventions, including genomic modifications and targeted biological agents. Historical success in managing long-term metabolic and cardiovascular conditions establishes credibility for supervising precision medicine applications. Digital innovations (e.g., remote consultation systems, algorithmic forecasting, and distributed ledger prescription tracking) enhance their capacity to coordinate fragmented services while responding to infectious outbreaks and polypharmacy challenges in elderly populations. This evolution promises decreased emergency admissions, improved therapeutic compliance, and more cost-effective care delivery. Regulatory reform must eliminate practice limitations, enabling these accessible professionals to address population health requirements fully.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"33050"},"PeriodicalIF":2.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing cisplatin chemosensitivity in gastric cancer through LINC00162 silencing: Modulation of the PI3K/AKT pathway and NANOG downregulation. 通过沉默LINC00162增强胃癌顺铂化疗敏感性:PI3K/AKT通路的调节和NANOG下调
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-04-19 eCollection Date: 2026-01-01 DOI: 10.34172/bi.32772
Seyed Ali Hosseini, Amir Ali Mokhtarzadeh, Saeid Ghorbian, Behzad Baradaran, Changiz Ahmadizadeh
{"title":"Enhancing cisplatin chemosensitivity in gastric cancer through LINC00162 silencing: Modulation of the PI3K/AKT pathway and NANOG downregulation.","authors":"Seyed Ali Hosseini, Amir Ali Mokhtarzadeh, Saeid Ghorbian, Behzad Baradaran, Changiz Ahmadizadeh","doi":"10.34172/bi.32772","DOIUrl":"10.34172/bi.32772","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy drugs serve as one of the primary treatments for gastric cancer. However, challenges, including drug resistance and adverse side effects of the chemotherapy drugs like cisplatin, limit their efficacy. Long non-coding RNAs (lncRNAs) have been increasingly recognized as important regulators in oncogenesis and drug response. In this study, the potential effect of the long non-coding RNA LINC00162 (PICSAR) on modulating the chemosensitivity of gastric cancer cells to cisplatin was investigated. Furthermore, the impact of the LINC00162 silencing on cellular responses was evaluated under two conditions: after the siRNA-mediated silencing of the LINC00162 alone, and after combined treatment with cisplatin.</p><p><strong>Methods: </strong>Firstly, the viability of the cells following siRNA-mediated LINC00162 silencing, treatment with cisplatin, and the combination of both was evaluated. Half inhibitory concentration (IC<sub>50</sub>) of the cisplatin chemotherapy drug was assessed individually and after silencing of the LINC00162 via siRNA. Additionally, we investigated apoptosis, cell cycle arrest, migration, and colony formation in the cancer cells following the combination treatment. Finally, the effect of the combination treatment on the expression of the genes involved in these pathways, including <i>BAX, BCL2, TP53, MMP-9, CASP3, CASP9, AKT, PI3K,</i> and <i>NANOG</i> was evaluated by qRT-PCR.</p><p><strong>Results: </strong>Findings indicated that LINC00162 silencing increased the sensitivity of the AGS gastric cancer cells to cisplatin and reduced the IC<sub>50</sub> of cisplatin from 19.24 µg/mL to 14.08 µg/mL. Furthermore, LINC00162 siRNA induced apoptosis, increasing the apoptosis rate to 10.69% compared to 6.19% in the control group, and also caused sub-G<sub>1</sub> cell cycle arrest (3.94%). This effect was significantly enhanced in the combination treatment group (apoptosis: 41.7% and Sub-G1 arrest: 17.3%) compared to the control group or either single treatment. Moreover, our study demonstrated that siRNA-mediated inhibition of the LINC00162, both individually and in combination with cisplatin, decreased the migration and colony formation ability of AGS cancer cells.</p><p><strong>Conclusion: </strong>These findings suggest that targeting LINC00162 may potentially enhance the efficacy of cisplatin in gastric cancer cells and may represent a promising therapeutic strategy for gastric cancer.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"32772"},"PeriodicalIF":2.5,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhanced anticancer efficacy of α-lipoic acid-loaded TPGS micelles: Synthesis, characterization, and evaluation in a 4T1 breast cancer model. α-硫辛酸负载的TPGS胶束增强抗癌功效:合成、表征和在4T1乳腺癌模型中的评价
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-04-13 eCollection Date: 2026-01-01 DOI: 10.34172/bi.31242
Aqeel Akab Sarhan, Ismaeil Haririan, Mohammad Akrami, Fatemeh Saadatnia, Zigang Ge
{"title":"Enhanced anticancer efficacy of α-lipoic acid-loaded TPGS micelles: Synthesis, characterization, and evaluation in a 4T1 breast cancer model.","authors":"Aqeel Akab Sarhan, Ismaeil Haririan, Mohammad Akrami, Fatemeh Saadatnia, Zigang Ge","doi":"10.34172/bi.31242","DOIUrl":"10.34172/bi.31242","url":null,"abstract":"<p><strong>Introduction: </strong>α-Lipoic acid (ALA) is a potent antioxidant with anticancer properties, but its clinical application is limited by poor water solubility and low bioavailability. Current nanocarrier systems for ALA delivery suffer from low encapsulation efficiency, rapid drug release kinetics, and biocompatibility concerns that restrict their therapeutic potential. This study aimed to develop and evaluate ALA-loaded D-alpha-tocopheryl polyethylene glycol succinate (TPGS) micelles as an innovative nanomedicine platform to overcome existing limitations and enhance anticancer efficacy.</p><p><strong>Methods: </strong>ALA was loaded into TPGS micelles via modified solvent evaporation method and comprehensively characterized by TEM, DLS, and FTIR examination. Drug loading and encapsulation efficiency were quantitatively determined. <i>In vitro</i> drug release kinetics, cellular uptake and cytotoxicity were assessed in 4T1 breast cancer cells. Gene expression analysis was performed, and <i>in vivo</i> antitumor efficacy was evaluated in 4T1 murine xenograft model with histopathological examination.</p><p><strong>Results: </strong>The formulation achieved superior encapsulation efficiency of 70%, with DLS analysis revealing micelles having mean diameter of 30-40 nm (polydispersity index: 0.234) and zeta potential of -1.9 mV. TEM confirmed spherical morphology. FTIR validated structural integrity with characteristic peaks. <i>In vitro</i> release demonstrated burst release of 52.4±2.5% (6 hours) followed by sustained release reaching 85.9±2.5% (48 hours). Flow cytometry showed 13.75-fold increased cellular uptake (15.4% vs 1.12% FL4-H+cells). MTT assay revealed dose-dependent cytotoxicity. qRT-PCR demonstrated significant upregulation of apoptotic markers: Caspase-8 (2.071-fold, 95% CI: 1.308-3.299, <i>P</i><0.001) and Caspase-9 (2.86-fold, 95% CI: 1.102-7.785, <i>P</i><0.001). <i>In vivo</i> studies in 4T1 murine xenograft model showed 10.39% reduction in tumor growth rate (8.54±3.83 mm³/day vs 9.53±1.03 mm³/day in controls) with histopathological evidence of decreased mitotic activity (28 vs 36 mitoses/10 HPF) and increased apoptosis (11 vs 5 apoptotic figures/10 HPF). All treatment groups achieved 100% survival throughout the 17-day study period with maintained body weights, confirming excellent biocompatibility.</p><p><strong>Conclusion: </strong>ALA-loaded TPGS micelles demonstrate enhanced anticancer efficacy through improved drug delivery, controlled release kinetics, and effective modulation of apoptotic pathways, supporting their potential for clinical translation in cancer therapy.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"31242"},"PeriodicalIF":2.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long non-coding RNA PURPL in cancer and cellular regulation: Mechanistic insights and therapeutic potential. 长链非编码RNA PURPL在癌症和细胞调控中的作用:机制见解和治疗潜力。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.34172/bi.33252
Nazila Valatabar, Reza Safaralizadeh, Amir Ali Mokhtarzadeh, Mohammad Ali Hosseinpour Feizi
{"title":"Long non-coding RNA PURPL in cancer and cellular regulation: Mechanistic insights and therapeutic potential.","authors":"Nazila Valatabar, Reza Safaralizadeh, Amir Ali Mokhtarzadeh, Mohammad Ali Hosseinpour Feizi","doi":"10.34172/bi.33252","DOIUrl":"10.34172/bi.33252","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) constitute a large fraction of the mammalian transcriptome and are increasingly recognized as critical regulators of gene expression and cellular homeostasis. Dysregulation of lncRNAs has been strongly implicated in cancer initiation and progression. <i>PURPL</i> (p53-upregulated regulator of p53 levels) is an emerging oncogenic lncRNA that plays a pivotal role in modulating multiple cancer-related cellular pathways, including the p53 signaling pathway, autophagy, miRNA-mediated gene regulation, genome stability, cellular senescence, and metastasis. Mechanistically, <i>PURPL</i> orchestrates signaling networks and epigenetic regulation via diverse molecular modes, functioning as a competing endogenous RNA (ceRNA), molecular scaffold, and guide, thereby influencing gene expression and cellular homeostasis. Functional studies reveal that suppression of <i>PURPL</i> enhances chemosensitivity, inhibits tumor cell proliferation and migration, and induces apoptosis across multiple cancer types. This review systematically summarizes the molecular mechanisms underlying <i>PURPL</i>-mediated regulation and highlights its multifaceted roles in cancer biology, thereby providing an integrative view of its functions in tumorigenesis and cellular regulation.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"33252"},"PeriodicalIF":2.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies. 检查点抑制及其后:眼部恶性肿瘤免疫特权景观的精确免疫工程。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.34172/bi.33219
Qamar Abuhassan, Kamel Saleh, S Renuka Jyothi, Radhamadhab Sahoo, P Prakash, Gunjan Mukherjee, Aashna Sinha, Turabek Boyqulov
{"title":"Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.","authors":"Qamar Abuhassan, Kamel Saleh, S Renuka Jyothi, Radhamadhab Sahoo, P Prakash, Gunjan Mukherjee, Aashna Sinha, Turabek Boyqulov","doi":"10.34172/bi.33219","DOIUrl":"10.34172/bi.33219","url":null,"abstract":"<p><p>Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body's most immunologically constrained ecosystems, the eye's immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmatically regulated within ocular tissue. We synthesize recent advances in bispecific T-cell engagers, oncolytic viro-immunotherapy, mRNA and dendritic-cell vaccines, and engineered CAR/TCR-T platforms, highlighting how they collectively reconfigure the ocular tumor microenvironment from immune-silent to immune-responsive. Logic-gated antibodies, ROS-responsive nanocarriers, and CRISPR-assisted checkpoint reprogramming are added to the notion of \"precision immune engineering\". These developments are intended to temporarily alter immune privilege without sacrificing visual quality. Lastly, we suggest a systems-level model for ocular immuno-oncology 2.0, where immune privilege is not an unchangeable barrier but rather a configurable circuit for therapeutic orchestration. One element of a dynamic, closed-loop immune-engineering architecture is checkpoint inhibition. This platform offers the possibility of long-lasting, vision-preserving disease treatment by combining AI-driven neoantigen detection, liquid-biopsy feedback loops, and flexible delivery biomaterials. While several of these approaches remain at a conceptual or early translational stage, they outline a plausible roadmap toward vision-preserving immunotherapy in ocular oncology.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"33219"},"PeriodicalIF":2.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-level lasers can improve spermatogenesis in infertile mice by targeting molecular pathways. 低水平激光可以通过靶向分子途径改善不育小鼠的精子发生。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-02-25 eCollection Date: 2026-01-01 DOI: 10.34172/bi.31018
Habib Tajalli, Masoud Maleki, Fatemeh Firouzi Amoudizaj, Zahra Akbarpour, Esmail Safavi, Reza Shahi, Alireza Sotoudeh, Ahmad Babazadeh Bedoustani
{"title":"Low-level lasers can improve spermatogenesis in infertile mice by targeting molecular pathways.","authors":"Habib Tajalli, Masoud Maleki, Fatemeh Firouzi Amoudizaj, Zahra Akbarpour, Esmail Safavi, Reza Shahi, Alireza Sotoudeh, Ahmad Babazadeh Bedoustani","doi":"10.34172/bi.31018","DOIUrl":"10.34172/bi.31018","url":null,"abstract":"<p><strong>Introduction: </strong>Infertility affects approximately 15% of couples worldwide, with male factors accounting for approximately half of the cases. Low-level laser therapy (LLLT) has been increasingly considered in modern medicine due to its high efficacy, ease of use, and lack of side effects. Evidence suggests that this method can prevent DNA damage in cells and activate key genes related to fertility. This study aimed to investigate the effects of LLLT on sperm production in azoospermic mice using in vitro and in vivo experimental models.</p><p><strong>Methods: </strong>Adult male NMRI mice (8-9 weeks old, 30-35 g) were divided into the negative control (healthy), positive control (azoospermia via intraperitoneal busulfan, 30 mg/kg), and experimental (azoospermia with 808 nm LLLT at 8 J/cm<sup>2</sup>) groups (8 mice per group) for in vivo experiments. For the in vitro part, spermatogonial stem cells were cultured from 6 azoospermic mice under control conditions or treated with laser (808 nm LLLT at 4 J/cm<sup>2</sup>). Morphological examination and real-time polymerase chain reaction were used to assess testicular structure and expression of several genes, such as deleted in azoospermia-like (<i>DAZL</i>), G protein-coupled receptor 125 (<i>GPR125</i>), synaptonemal complex protein 3 (<i>SYCP3</i>), DEAD-box helicase 4 (<i>VASA/DDX4</i>), protamine (<i>PRM</i>), acrosin (<i>ACR</i>), and tripartite motif containing 36 (<i>Haprin/TRIM36</i>).</p><p><strong>Results: </strong>In vivo, LLLT increased <i>VASA</i> expression, improved germ cell activity, and increased sperm production compared with untreated azoospermic control groups, although these changes were not statistically significant. In vitro, 4 J/cm<sup>2</sup> radiation modulated several genes related to spermatogenesis, supporting its role in germ cell differentiation.</p><p><strong>Conclusion: </strong>LLLT with a wavelength of 808 nm could improve spermatogenesis and sperm production in a mouse model of busulfan-induced azoospermia in vivo and in vitro. These results demonstrated its potential as a supportive treatment for male infertility.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"31018"},"PeriodicalIF":2.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Three-dimensional bioprinted hydrogels for the management of diabetic wounds: A review. 三维生物打印水凝胶用于糖尿病伤口的治疗:综述。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-02-24 eCollection Date: 2026-01-01 DOI: 10.34172/bi.32751
Piyali Khamkat, Bramhajit Chatterjee, Sourav Ghosh, Bhupendra Prajapati, Biswajit Basu, Sudarshan SIngh
{"title":"Three-dimensional bioprinted hydrogels for the management of diabetic wounds: A review.","authors":"Piyali Khamkat, Bramhajit Chatterjee, Sourav Ghosh, Bhupendra Prajapati, Biswajit Basu, Sudarshan SIngh","doi":"10.34172/bi.32751","DOIUrl":"10.34172/bi.32751","url":null,"abstract":"<p><p>Globally, the prevalence of diabetes mellitus (DM), a chronic metabolic disease, is at its peak. Type 2 diabetes (T2D) is more common worldwide, which raises the risk of ulcers and chronic healing, or non-healing wounds. Overall 15% to 20% of people with diabetes develop diabetic foot ulcers (DFUs), which is a significant consequence. Managing and treatment of wounds require an advancement of novel healing therapies with the use of biological dressings. The development of DFU wound dressings and the biomanufacturing of composite 3D skin substitutes are examples of 3D bioprinting technology for enhancing therapeutic approaches. These approaches and challenges of bioprinting technology in wound healing of chronic DFUs are covered in this review. Moreover, the review highlights the selection of biomaterials, integration of biomimetic approaches, and the ability of 3D bioprinting to replicate native skin architecture. Despite significant advances, the review identifies critical gaps including limited vascularization in printed constructs, standardization issues, and scalability challenges that impede clinical translation. Emerging biotechnological tools and novel biomaterial developments are also discussed, emphasizing their potential to overcome these limitations and improve DFU wound management.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"32751"},"PeriodicalIF":2.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Celastrol overcomes 5-fluorouracil resistance in osteosarcoma cells through p53-mediated apoptotic pathway modulation and P-glycoprotein inhibition: A comprehensive mechanistic study. Celastrol通过p53介导的凋亡通路调节和p糖蛋白抑制克服骨肉瘤细胞5-氟尿嘧啶耐药:一项全面的机制研究。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-02-18 eCollection Date: 2026-01-01 DOI: 10.34172/bi.32819
Mohammad Ebrahimnezhad, Amir Valizadeh, Bahman Yousefi, Dariush Shanehbandi
{"title":"Celastrol overcomes 5-fluorouracil resistance in osteosarcoma cells through p53-mediated apoptotic pathway modulation and P-glycoprotein inhibition: A comprehensive mechanistic study.","authors":"Mohammad Ebrahimnezhad, Amir Valizadeh, Bahman Yousefi, Dariush Shanehbandi","doi":"10.34172/bi.32819","DOIUrl":"10.34172/bi.32819","url":null,"abstract":"<p><strong>Introduction: </strong>Osteosarcoma, a prevalent malignant bone tumor in children and adolescents, is hindered by chemoresistance, particularly to 5-fluorouracil (5-FU), driven by mechanisms such as P-glycoprotein (P-gp) overexpression and altered p53 signaling. Celastrol, a triterpenoid, exhibits anti-tumor properties, but its potential to overcome 5-FU resistance in osteosarcoma remains underexplored.</p><p><strong>Methods: </strong>We investigated the synergistic effects of celastrol and 5-FU in human osteosarcoma cell lines with varying p53 statuses (U-2OS, wild-type; SaOS-2, p53-null; HOS, mutant p53) using MTT assays for cytotoxicity, Chou-Talalay method for synergy, and Cell Death Detection ELISA for apoptosis. Gene expression (p53, Bax, Bcl-2, caspase-9) was quantified via qRT-PCR, P-gp levels by Western blot, and P-gp efflux activity by Rhodamine 123 assays. Non-malignant hFOB 1.19 cells served as controls.</p><p><strong>Results: </strong>Celastrol and 5-FU exhibited potent cytotoxicity, with combination therapy reducing IC₅₀ values 3.7- to 11.9-fold across cell lines, showing strong synergy. The combination significantly enhanced apoptosis and modulated p53-dependent (U-2OS) and -independent (SaOS-2, HOS) pathways, upregulating Bax and caspase-9 while downregulating Bcl-2. Celastrol reduced P-gp expression and increased intracellular drug accumulation, comparable to verapamil.</p><p><strong>Conclusion: </strong>Celastrol synergizes with 5-FU to overcome chemoresistance in osteosarcoma by enhancing p53-mediated and -independent apoptosis and inhibiting P-gp-mediated drug efflux. These findings suggest a promising low-toxicity therapeutic strategy, warranting further in vivo and clinical investigations.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"32819"},"PeriodicalIF":2.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic effects of phytochemical cocktail and aerobic exercise on mRNA and lncRNA networks modulating bone turnover in hypothyroid mice. 植物化学混合物和有氧运动对调节甲状腺功能减退小鼠骨转换的mRNA和lncRNA网络的协同作用。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-02-14 eCollection Date: 2026-01-01 DOI: 10.34172/bi.30303
Malihe Bakhti, Farzaneh Taghian, Khosro Jalali Dehkordi, Rezvan Mirsafaei Rizi
{"title":"Synergistic effects of phytochemical cocktail and aerobic exercise on mRNA and lncRNA networks modulating bone turnover in hypothyroid mice.","authors":"Malihe Bakhti, Farzaneh Taghian, Khosro Jalali Dehkordi, Rezvan Mirsafaei Rizi","doi":"10.34172/bi.30303","DOIUrl":"10.34172/bi.30303","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic bone disease (MBD) is a multifactorial condition that leads to microarchitectural and bone mass disturbance. The association and mechanisms between MBD and hypothyroidism are not comprehensively elucidated. Moreover, long non-coding RNAs (lncRNAs), as critical regulators in biological processes, are one category of RNAs that could regulate gene expression through various mechanisms.</p><p><strong>Methods: </strong>Artificial intelligence indicated several mRNAs-lncRNAs involved in the bone tissue in hypothyroidism conditions. After in-silico and chemoinformatic analysis, 30 female C57BL/6 mice at six weeks old and an approximate weight of 24±2 g were divided into five subgroups (n=6 mice/groups), including 1) hypothyroidism in mice (HYPO), 2) hypothyroidism in mice treated with <i>Dorema aucheri</i> (DA) extract (0.4 mg/kg), 3) hypothyroidism in mice treated with aerobic exercise (AE), 4) hypothyroidism in mice treated DA extract bioactive compound along with AE, 5) Normal group (without any induction and treatments). Real-Time PCR detected the relative expression of <i>mRNA</i> and <i>lncRNAs</i>.</p><p><strong>Results: </strong>We indicated that the osteoblast and osteoclast markers are dysregulated in hypothyroidism. In addition, DA and AE modified the bone remodeling, bone resorption markers, and inhibitors of Wnt/beta-catenin. We revealed that <i>Adipoq</i>, <i>Dnmt1</i>, <i>Sirt-1, Ppar-ɑ</i>, <i>Ncor1</i>, and <i>Ctnnb1</i> networks are dysregulated in hypothyroidism conditions. DA and AE modulated this network in bone tissue. The relative expression of the four lncRNAs (TUG1, HOTAIR, H19, and MEG3) was altered in hypothyroidism. Notably, DA and AE significantly regulated the expression level of these lncRNAs.</p><p><strong>Conclusion: </strong>AE and DA complementary and alternative medicine ameliorated the metabolic bone disease induced by hypothyroidism in mice.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"30303"},"PeriodicalIF":2.5,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Moroccan virgin olive oil triterpenes: HPLC-DAD-ELSD profiling and computational investigation of anti-diabetic potential. 摩洛哥初榨橄榄油三萜:HPLC-DAD-ELSD分析和抗糖尿病潜力的计算研究。
IF 2.5 4区 工程技术
Bioimpacts Pub Date : 2026-01-05 eCollection Date: 2026-01-01 DOI: 10.34172/bi.31007
Meryem Boutalaka, Noureddine Ouazzani, Mohamed Ouabane, Panagiotis Stathopoulos, Abdelkrim Guendouzi, Hamid Maghat, Alexios-Leandros Skaltsounis, Tahar Lakhlifi, Mohammed Bouachrine
{"title":"Moroccan virgin olive oil triterpenes: HPLC-DAD-ELSD profiling and computational investigation of anti-diabetic potential.","authors":"Meryem Boutalaka, Noureddine Ouazzani, Mohamed Ouabane, Panagiotis Stathopoulos, Abdelkrim Guendouzi, Hamid Maghat, Alexios-Leandros Skaltsounis, Tahar Lakhlifi, Mohammed Bouachrine","doi":"10.34172/bi.31007","DOIUrl":"10.34172/bi.31007","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to impaired insulin secretion or resistance. Conventional treatments like acarbose, miglitol, and voglibose inhibit carbohydrate-digesting enzymes but often cause adverse effects and have bioavailability limitations. This has led to interest in plant-derived bioactive compounds as safer alternatives. Oleanolic and maslinic acids in Moroccan virgin olive oil have shown potent inhibitory activity against α-glucosidase and α-amylase, enzymes regulating postprandial glucose levels.</p><p><strong>Methods: </strong>This study quantified the levels of oleanolic and maslinic acids in olive oils from various Moroccan regions, considering factors such as olive variety, maturity index, production method, and geographic origin. Pharmacokinetic properties were assessed using in silico ADME analysis. Molecular docking was performed to evaluate inhibitory interactions with α-amylase and α-glucosidase. Molecular dynamics (MD) simulations (1000 ns) assessed complex stability, and MM-PBSA calculations determined binding free energies.</p><p><strong>Results: </strong>The concentrations of oleanolic and maslinic acids varied across olive oil samples. The Moroccan Picholine variety had the highest levels (58.3 mg/kg for maslinic acid and 55.06 mg/kg for oleanolic acid). Olive oil from the two-phase milling method contained higher concentrations than the three-phase system, and lower maturity index olives showed greater concentrations. Pharmacokinetic analysis indicated favorable drug-likeness properties for these bioactive compounds. In silico docking suggested notable binding of maslinic acid to α-amylase (-41.42 kJ/mol) and oleanolic acid to α-glucosidase (-32.22 kJ/mol), with interactions involving key amino acid residues. Molecular dynamics simulations indicated stable ligand-enzyme interactions, and MM-PBSA analysis estimated binding energies of -39.05±16.78 kJ/mol for the maslinic acid-α-amylase complex and -13.97±7.08 kJ/mol for the oleanolic acid-α-glucosidase complex.</p><p><strong>Conclusion: </strong>Moroccan virgin olive oil, rich in oleanolic and maslinic acids, may serve as a natural alternative for diabetes management by modulating key enzymatic pathways involved in glucose metabolism.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"16 ","pages":"31007"},"PeriodicalIF":2.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13056887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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