Saman Heydari, Mohammad Barzegar-Jalali, Mostafa Heydari, Afsaneh Radmehr, A. C. Paiva-Santos, M. Kouhsoltani, Hamed Hamishehkar
Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models.
{"title":"The impact of particle size of nanostructured lipid carriers on follicular drug delivery: A comprehensive analysis of mouse and human hair follicle penetration","authors":"Saman Heydari, Mohammad Barzegar-Jalali, Mostafa Heydari, Afsaneh Radmehr, A. C. Paiva-Santos, M. Kouhsoltani, Hamed Hamishehkar","doi":"10.34172/bi.2024.30243","DOIUrl":"https://doi.org/10.34172/bi.2024.30243","url":null,"abstract":"Introduction: Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Methods: Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. Results: The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. Conclusion: The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya-Lin Han, Li Chen, Xu-Ning Wang, Mao-Lin Xu, Rui Qin, F. Gong, Peng Sun, Hong-yi Liu, Zhi-Peng Teng, Zhao-Xia Li, Guang-Hai Dai
Background: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the Notch and RTK-RAS signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.
研究背景目的：探讨 III 期胃癌（GC）患者的肿瘤突变负荷（TMB）与预后的相关性及其临床意义。研究方法在38名患者组成的研究队列和173名患者组成的癌症基因组图谱（TCGA）队列中，III期胃癌患者被分为高TMB组和低TMB组。在研究队列中，使用新一代测序技术检测突变的 GC 基因并获得 TMB 数据。在TCGA队列中，进行了基因组富集分析，并分析了TMB、预后和临床病理因素之间的关系。采用 Western 印迹和定量实时聚合酶链反应检测蛋白质和基因的表达水平。使用甲基噻唑四氮唑和透孔细胞检测法测量细胞活力。结果显示在两个队列中，高TMB组患者的总生存率（OS）均优于低TMB组患者，且TMB与年龄、突变特征1和突变特征17相关。Cox 回归分析显示，年龄而非 TMB 是独立的预后因素。此外，高频突变基因明显富集于Notch和RTK-RAS信号通路。与低TMB组相比，高TMB组这些通路的激活程度较低，而两组GC细胞的增殖和迁移能力显示出相似的模式。结论高TMB组患者的OS率高于低TMB组患者。高频突变基因明显富集于 RTK-RAS 和 Notch 通路。因此，TMB可作为一种预后生物标志物，具有潜在的临床意义。
{"title":"Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer","authors":"Ya-Lin Han, Li Chen, Xu-Ning Wang, Mao-Lin Xu, Rui Qin, F. Gong, Peng Sun, Hong-yi Liu, Zhi-Peng Teng, Zhao-Xia Li, Guang-Hai Dai","doi":"10.34172/bi.2024.30118","DOIUrl":"https://doi.org/10.34172/bi.2024.30118","url":null,"abstract":"Background: To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC). Methods: Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays. Results: Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the Notch and RTK-RAS signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups. Conclusion: Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140267667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.
α-硫辛酸（ALA）因其对多种健康状况的潜在治疗效果而备受关注。尽管 ALA 具有显著的抗氧化特性，但生物利用率低、半衰期短、气味难闻等问题阻碍了它的发展。为了克服这些限制并提高 ALA 的疗效，人们探索了各种纳米颗粒给药系统。本综述评估了不同纳米颗粒载体在 ALA 给药中的应用，包括脂基纳米颗粒（固体脂质纳米颗粒、niosomes、脂质体、纳米结构脂质载体（NLCs）和胶束）、纳米乳液、聚合物纳米颗粒（纳米胶囊、PEG 化纳米颗粒和聚己内酯纳米颗粒）、薄膜、纳米纤维和金纳米颗粒。每种纳米颗粒系统都具有独特的优势，如稳定性更好、可持续释放、生物利用度更高以及可定向给药。例如，载入 ALA 的 SLNs 在护肤产品和嫩肤方面表现出了优势。封装在niosomes中的ALA具有治疗脑缺血的潜力，脑缺血在很大程度上与中风有关。装载 ALA 的阳离子纳米乳剂有望用于眼科，减少血管损伤和角膜疾病。用壳聚糖包裹脂质体可进一步提高稳定性和性能，促进药物通过皮肤的吸收。本综述全面概述了 ALA 纳米颗粒给药系统的进展，强调了其克服 ALA 给药局限性并显著提高疗效的潜力。这些创新方法有望开发出更好的基于 ALA 的治疗方法，广泛应用于各种健康状况。
{"title":"A comprehensive review on alpha-lipoic acid delivery by nanoparticles","authors":"Navid Mosallaei, Amirhossein Malaekeh-Nikouei, Setayesh Sarraf Shirazi, Javad Behmadi, B. Malaekeh-Nikouei","doi":"10.34172/bi.2024.30136","DOIUrl":"https://doi.org/10.34172/bi.2024.30136","url":null,"abstract":"Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140430949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. Bahadoran, P. Mirmiran, Fereidoun Azizi, A. Ghasemi
Introduction: We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years. Methods: This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio. Results: Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (Ptime×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018). Conclusion: A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.
引言：我们的目的是追踪糖尿病前期（Pre-DM）受试者血糖状态的纵向变化与其全身一氧化氮（NO）产生的基线水平（即用一氧化氮测量）的关系：我们旨在追踪糖尿病前期（Pre-DM）受试者血糖状态的纵向变化与其全身一氧化氮（NO）产生的基线水平[即以血清一氧化氮代谢物（NOx）、经粗略和体重（BW）调整的一氧化氮与肌酐的比率（NOx-to-Cr）来衡量]在9年时间里的关系。研究方法这项队列研究纳入了 541 名患有糖尿病前期的伊朗中年男子和妇女，他们于 2006-2008 年被招募，并随访至 2015-2017 年。采用比色格里斯法测定血清氮氧化物浓度。多叉逻辑回归分析估算了血清氮氧化物、粗比率和体重调整后的氮氧化物与铬比率的三等分（三等分 3 与三等分 1 和三等分 2）Pre-DM 回归和进展的几率比（OR）。结果：与发展为 2 型糖尿病（T2D）或仍为糖尿病前期（0.52±0.34 vs. 0.43±0.25 和 0.48±0.29，P=0.023）的患者相比，血糖恢复正常（NG）的患者具有更高的体重调整后氮氧化物-Cr 比值。体重调整后的 NOx-to-Cr 越高，恢复到 NG 的几率越大（OR=2.05，95% CI=0.98-4.32，P=0.058），随着时间的推移，2h 血清葡萄糖水平降低（Ptime×group=0.025），以及空腹血糖（106，95% CI=103-109 vs. 110，95% CI=108-112 mg/dL，P=0.008）和 2 小时血清血糖（153，95% CI=146-159 vs. 163，95% CI=158-168 mg/dL，P=0.018）的总体平均值下降。结论DM前期受试者的内源性氮氧化物产生量较高（即通过体重和Cr调整后的血清氮氧化物浓度间接测量）与恢复NG的几率有关。
{"title":"Systemic nitric oxide metabolites and the chance of pre-diabetes regression to normoglycemia: A 9-year cohort study","authors":"Z. Bahadoran, P. Mirmiran, Fereidoun Azizi, A. Ghasemi","doi":"10.34172/bi.2024.29917","DOIUrl":"https://doi.org/10.34172/bi.2024.29917","url":null,"abstract":"Introduction: We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years. Methods: This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio. Results: Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (Ptime×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018). Conclusion: A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140456555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seyedeh-Sara Hashemi, Mohsen Pirmoradi, Alireza Rafati, Mehdi Kian, Avishan Mohammadi, Mohamad Ali Hoghoughi
Introduction: Flexor tendon injuries are common and require surgery. Acellular dermal matrix (ADM) is a natural graft used to repair tissues, though infections represent the primary cause of its therapeutic failure. In this study, zinc oxide nanoparticles (ZnO-NPs) were coated on the ADM in order to add antibacterial potential as well as enhance healing properties. Also, the produced ADM/ZnO-NPs graft was applied to accelerate fifth zone flexor tendon repair following the reconstructive surgery. Methods: Morphological, mechanical, cell viability, and antibacterial tests were performed to evaluate the physical and biological properties of the fabricated ADM/ZnO-NPs graft. For clinical evaluations, 20 patients with a flexor tendon injury in zone 5 were randomly divided into control and treatment with ADM/ZnO-NPs groups (n=10 each). The control group had routine reconstructive surgery, while the other group received the ADM/ZnO- NPs graft during their surgery. Postoperative functional outcomes were evaluated 4, 6, and 8 weeks following the tendon repair surgery according to the Buck-Gramcko II criteria. Results: The ADM/ZnO-NPs had natural derm specifications as well as dense and integrated morphology with intermediate antibacterial properties. According to the Buck- Gramcko II criteria, the postoperative functional outcome scores were significantly higher in the ADM/ZnO-NPs group in comparison with the control group at 4 (P<0.01), 6 (P<0.01), and 8 (P<0.001) weeks after the surgery. Conclusion: The present findings revealed that the ADM/ZnO-NPs graft can accelerate the healing of the damaged tendon without common post-operative functional complications and adhesions following the tendon repair surgery. However, more comprehensive clinical trials are still needed.
{"title":"A human acellular dermal matrix coated with zinc oxide nanoparticles accelerates tendon repair in patients with hand flexor tendon injuries in zone 5 of the hand","authors":"Seyedeh-Sara Hashemi, Mohsen Pirmoradi, Alireza Rafati, Mehdi Kian, Avishan Mohammadi, Mohamad Ali Hoghoughi","doi":"10.34172/bi.2024.27748","DOIUrl":"https://doi.org/10.34172/bi.2024.27748","url":null,"abstract":"Introduction: Flexor tendon injuries are common and require surgery. Acellular dermal matrix (ADM) is a natural graft used to repair tissues, though infections represent the primary cause of its therapeutic failure. In this study, zinc oxide nanoparticles (ZnO-NPs) were coated on the ADM in order to add antibacterial potential as well as enhance healing properties. Also, the produced ADM/ZnO-NPs graft was applied to accelerate fifth zone flexor tendon repair following the reconstructive surgery. Methods: Morphological, mechanical, cell viability, and antibacterial tests were performed to evaluate the physical and biological properties of the fabricated ADM/ZnO-NPs graft. For clinical evaluations, 20 patients with a flexor tendon injury in zone 5 were randomly divided into control and treatment with ADM/ZnO-NPs groups (n=10 each). The control group had routine reconstructive surgery, while the other group received the ADM/ZnO- NPs graft during their surgery. Postoperative functional outcomes were evaluated 4, 6, and 8 weeks following the tendon repair surgery according to the Buck-Gramcko II criteria. Results: The ADM/ZnO-NPs had natural derm specifications as well as dense and integrated morphology with intermediate antibacterial properties. According to the Buck- Gramcko II criteria, the postoperative functional outcome scores were significantly higher in the ADM/ZnO-NPs group in comparison with the control group at 4 (P<0.01), 6 (P<0.01), and 8 (P<0.001) weeks after the surgery. Conclusion: The present findings revealed that the ADM/ZnO-NPs graft can accelerate the healing of the damaged tendon without common post-operative functional complications and adhesions following the tendon repair surgery. However, more comprehensive clinical trials are still needed.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140457356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sari Eka Pratiwi, Ysrafil Ysrafil, Mardhia Mardhia, Mahyarudin Mahyarudin, M. I. Ilmiawan, Heru Fajar Trianto, Delima Fajar Liana, Yuri Amia
Introduction: The current vaccine strategies to prevent cervical cancer are effective only for individuals unexposed to HPV, lacking therapeutic effects against pre-existing infections. Multiepitope vaccines, using an immunoinformatic approach, are promising against tumors and viral infections because of their high specificity, safety, and stability, as well as the cheap cost of development. Methods: This study employed computer-based immunoinformatic analysis to design therapeutic multiepitope vaccines against cervical cancer using oncoproteins E6 and E7 of HPV 16 and 18. Several immunoinformatic tools were applied to analyze potential vaccine constructs capable of stimulating immune responses against both oncoproteins. Results: The constructed vaccine exhibited antigenic, immunogenic, nonallergenic, nontoxic, stable, and soluble characteristics. Additionally, it effectively interacted with TLR2 and TLR4, showing high binding capacity. Computational analysis indicated the vaccine could induce immune responses through the elevation of cytokine levels after the third injection, antibody production, activation of memory B and T cells, and promotion of increased dendritic cell counts. Conclusion: The novel multiepitope vaccine based on E6 and E7 presented as a promising candidate for combating HPV infections and associated cervical cancer. Further in vitro and in vivo studies were essential to validate the efficacy and safety of the vaccine.
{"title":"A novel therapeutic multiepitope vaccine based on oncoprotein E6 and E7 of HPV 16 and 18: An in silico approach","authors":"Sari Eka Pratiwi, Ysrafil Ysrafil, Mardhia Mardhia, Mahyarudin Mahyarudin, M. I. Ilmiawan, Heru Fajar Trianto, Delima Fajar Liana, Yuri Amia","doi":"10.34172/bi.2024.27846","DOIUrl":"https://doi.org/10.34172/bi.2024.27846","url":null,"abstract":"Introduction: The current vaccine strategies to prevent cervical cancer are effective only for individuals unexposed to HPV, lacking therapeutic effects against pre-existing infections. Multiepitope vaccines, using an immunoinformatic approach, are promising against tumors and viral infections because of their high specificity, safety, and stability, as well as the cheap cost of development. Methods: This study employed computer-based immunoinformatic analysis to design therapeutic multiepitope vaccines against cervical cancer using oncoproteins E6 and E7 of HPV 16 and 18. Several immunoinformatic tools were applied to analyze potential vaccine constructs capable of stimulating immune responses against both oncoproteins. Results: The constructed vaccine exhibited antigenic, immunogenic, nonallergenic, nontoxic, stable, and soluble characteristics. Additionally, it effectively interacted with TLR2 and TLR4, showing high binding capacity. Computational analysis indicated the vaccine could induce immune responses through the elevation of cytokine levels after the third injection, antibody production, activation of memory B and T cells, and promotion of increased dendritic cell counts. Conclusion: The novel multiepitope vaccine based on E6 and E7 presented as a promising candidate for combating HPV infections and associated cervical cancer. Further in vitro and in vivo studies were essential to validate the efficacy and safety of the vaccine.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140460874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Fe2O3 NPs can enter cells quickly, pass through the blood-brain barrier and interact with macromolecules. These materials are widely used in different fields, so their risk assessment is among the most critical issues. Acetylcholinesterase (AChE) is a cholinergic enzyme in central and peripheral nervous systems. Methods: In this work, the possible effects of Fe2O3 NPs on the structure and catalytic activity of AChE were investigated using circular dichroism (CD), surface plasmon resonance (SPR), and fluorescence spectroscopies. Results: The outcomes demonstrated that 5 nm Fe2O3 NPs inhibit AChE activity through mixed mechanism. While 50 nm Fe2O3 NPs caused an enhancement in the catalytic activity up to 60 nM. However, higher concentrations of Fe2O3 NPs (above 60 nM) hindered the enzyme activity via mixed mechanism. Fluorescence analysis showed that NPs can quench the fluorescence intensity of AChE that refer to conformational changes. Furthermore, CD results showed that Fe2O3 NPs can reduce the α-helix and β-sheet contents of the enzyme and decrease the stability of AChE. Also, the SPR data analysis showed that the affinity between AChE and Fe2O3 NPs decreased with rising temperature. After treatment with Fe2O3 NPs, the catalytic activity of AChE was assessed in HepG2 cell lines, and the results confirmed the inhibitory effects of Fe2O3 NPs on AChE activity in vivo. Conclusion: These findings provide helpful information about the impact of Fe2O3 NPs on the structure and function of AChE and could offer new insights into the risk assessment of the medical application of nanoparticles.
{"title":"The effects of Fe2O3 nanoparticles on catalytic function of human acetylcholinesterase: size and concentration role","authors":"Samaneh Rashtbari, Zahra Hassanpour Aydinlou, Leila Sadeghi","doi":"10.34172/bi.2024.29946","DOIUrl":"https://doi.org/10.34172/bi.2024.29946","url":null,"abstract":"Introduction: Fe2O3 NPs can enter cells quickly, pass through the blood-brain barrier and interact with macromolecules. These materials are widely used in different fields, so their risk assessment is among the most critical issues. Acetylcholinesterase (AChE) is a cholinergic enzyme in central and peripheral nervous systems. Methods: In this work, the possible effects of Fe2O3 NPs on the structure and catalytic activity of AChE were investigated using circular dichroism (CD), surface plasmon resonance (SPR), and fluorescence spectroscopies. Results: The outcomes demonstrated that 5 nm Fe2O3 NPs inhibit AChE activity through mixed mechanism. While 50 nm Fe2O3 NPs caused an enhancement in the catalytic activity up to 60 nM. However, higher concentrations of Fe2O3 NPs (above 60 nM) hindered the enzyme activity via mixed mechanism. Fluorescence analysis showed that NPs can quench the fluorescence intensity of AChE that refer to conformational changes. Furthermore, CD results showed that Fe2O3 NPs can reduce the α-helix and β-sheet contents of the enzyme and decrease the stability of AChE. Also, the SPR data analysis showed that the affinity between AChE and Fe2O3 NPs decreased with rising temperature. After treatment with Fe2O3 NPs, the catalytic activity of AChE was assessed in HepG2 cell lines, and the results confirmed the inhibitory effects of Fe2O3 NPs on AChE activity in vivo. Conclusion: These findings provide helpful information about the impact of Fe2O3 NPs on the structure and function of AChE and could offer new insights into the risk assessment of the medical application of nanoparticles.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140461550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Azin Shahmohammadi, Hadi Samadian, Saeed Heidari Keshel, Khodabakhsh Rashidi, Amir Kiani, Masoud Soleimani, Farjam Goudarzi
Introduction: Wound healing is a major therapeutic concern in regenerative medicine. The current study aimed to investigate the second-degree burn wound treatment in rats using rat adipose- derived stem cells (ADSCs) and manganese nanoparticles (MnO2–NPs) in a polycaprolactone/gelatin electrospun nanofiber scaffold. Methods: After the synthesis of nanoparticles and electrospinning of nanofibers, the SEM analysis, contact angle, mechanical strength, blood compatibility, porosity, swelling, biodegradability, cell viability, and adhesion assays were performed. According to the results, the PCL/Gel/5%MnO2-NPs nanofiber (Mn-5%) was determined to be the most suitable scaffold. The ADSCs-seeded Mn-5% scaffolds were applied as a burn wound dressing. The wound closure rate, IL-1β, and IL-6 level, hydroxyproline, and glycosaminoglycans content were measured, and the hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry stainings were carried out. Results: Based on the results, in Mn+S (ADSCs+PCL/Gel/5%MnO2-NPs nanofiber) and N+S (ADSCs+PCL/Gel nanofiber) groups, the IL-6 and IL-1β levels were reduced, and the percentage of wound closure, glycosaminoglycans, and hydroxyproline content were increased compared to the control group (P<0.05). Also, the lowest amount of α-SMA was observed in these two groups, demonstrating stem cells' role in reducing α-SMA levels and thus preventing fibrosis. Moreover, the amount of α-SMA in the Mn+S group is lower than in the N+S group and, is closer to healthy skin. According to histology results, the best type of treatment was observed in the Mn+S group. Conclusion: In conclusion, the ADSCs-seeded PCL/Gel/5%MnO2-NPs scaffold demonstrated considerable therapeutic effects in burn wound healing.
{"title":"Burn wound healing using adipose-derived mesenchymal stem cells and manganese nanoparticles in polycaprolactone/gelatin electrospun nanofibers in rats","authors":"Azin Shahmohammadi, Hadi Samadian, Saeed Heidari Keshel, Khodabakhsh Rashidi, Amir Kiani, Masoud Soleimani, Farjam Goudarzi","doi":"10.34172/bi.2024.30193","DOIUrl":"https://doi.org/10.34172/bi.2024.30193","url":null,"abstract":"Introduction: Wound healing is a major therapeutic concern in regenerative medicine. The current study aimed to investigate the second-degree burn wound treatment in rats using rat adipose- derived stem cells (ADSCs) and manganese nanoparticles (MnO2–NPs) in a polycaprolactone/gelatin electrospun nanofiber scaffold. Methods: After the synthesis of nanoparticles and electrospinning of nanofibers, the SEM analysis, contact angle, mechanical strength, blood compatibility, porosity, swelling, biodegradability, cell viability, and adhesion assays were performed. According to the results, the PCL/Gel/5%MnO2-NPs nanofiber (Mn-5%) was determined to be the most suitable scaffold. The ADSCs-seeded Mn-5% scaffolds were applied as a burn wound dressing. The wound closure rate, IL-1β, and IL-6 level, hydroxyproline, and glycosaminoglycans content were measured, and the hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry stainings were carried out. Results: Based on the results, in Mn+S (ADSCs+PCL/Gel/5%MnO2-NPs nanofiber) and N+S (ADSCs+PCL/Gel nanofiber) groups, the IL-6 and IL-1β levels were reduced, and the percentage of wound closure, glycosaminoglycans, and hydroxyproline content were increased compared to the control group (P<0.05). Also, the lowest amount of α-SMA was observed in these two groups, demonstrating stem cells' role in reducing α-SMA levels and thus preventing fibrosis. Moreover, the amount of α-SMA in the Mn+S group is lower than in the N+S group and, is closer to healthy skin. According to histology results, the best type of treatment was observed in the Mn+S group. Conclusion: In conclusion, the ADSCs-seeded PCL/Gel/5%MnO2-NPs scaffold demonstrated considerable therapeutic effects in burn wound healing.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140501454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Arvindekar, Sanket Rathod, Prafulla Choudhari, P. Mane, A. Arvindekar, Suraj N. Mali, B. Thorat
Introduction: The aromatase enzyme plays an important role in the progress of hormone-dependent breast cancer, especially in estrogen receptor-positive (ER+) breast cancers. In case of postmenopausal women, the aromatization of androstenedione to estrone in adipose tissue is the most important source of estrogen. Generally 60%-75% of pre- and post-menopausal women suffer from estrogen-dependent breast cancer, and thus suppressing estrogen has been recognized to be a successful therapy. Hence, to limit the stimulation of estrogen, aromatase inhibitors (AIs) are used in the second-line treatment of breast cancer. Methods: The present computational study employed an in silico approach in the identification of natural actives targeting the aromatase enzyme from a structurally diverse set of natural products. Molecular docking, QSAR studies and pharmacophore modeling were carried out using the VLife Molecular Design Suite (version 4.6). The stability of the compounds was confirmed by molecular dynamics. Results: From molecular docking and analysis of interactions with the amino acid residues of the binding cavity, it was found that the amino acid residues interacting with the non-steroidal inhibitors exhibited π-stacking interactions with PHE134, PHE 221, and TRP 224, while the steroidal drug exemestane lacked π-stacking interactions. QSAR studies were performed using the flavonoid compounds, in order to identify the structural functionalities needed to improve the anti-breast cancer activity. Molecular dynamics of the screened hits confirmed the stability of compounds with the target in the binding cavity. Moreover, pharmacophore modelling presented the pharmacophoric features of the selected scaffolds for aromatase inhibitory activity. Conclusion: The results presented 23 hit compounds that can be developed as anti-breast cancer modulating agents in the near future. Additionally, anthraquinone compounds with minor structural modification can also serve to be potential aromatase inhibitors. The in silico protocol utilised can be useful in the drug discovery process for development of new leads from structurally diverse set of natural products that are comparable to the drugs used clinically in breast cancer therapy.
{"title":"Computational studies and structural insights for discovery of potential natural aromatase modulators for hormone-dependent breast cancer","authors":"S. Arvindekar, Sanket Rathod, Prafulla Choudhari, P. Mane, A. Arvindekar, Suraj N. Mali, B. Thorat","doi":"10.34172/bi.2024.27783","DOIUrl":"https://doi.org/10.34172/bi.2024.27783","url":null,"abstract":"Introduction: The aromatase enzyme plays an important role in the progress of hormone-dependent breast cancer, especially in estrogen receptor-positive (ER+) breast cancers. In case of postmenopausal women, the aromatization of androstenedione to estrone in adipose tissue is the most important source of estrogen. Generally 60%-75% of pre- and post-menopausal women suffer from estrogen-dependent breast cancer, and thus suppressing estrogen has been recognized to be a successful therapy. Hence, to limit the stimulation of estrogen, aromatase inhibitors (AIs) are used in the second-line treatment of breast cancer. Methods: The present computational study employed an in silico approach in the identification of natural actives targeting the aromatase enzyme from a structurally diverse set of natural products. Molecular docking, QSAR studies and pharmacophore modeling were carried out using the VLife Molecular Design Suite (version 4.6). The stability of the compounds was confirmed by molecular dynamics. Results: From molecular docking and analysis of interactions with the amino acid residues of the binding cavity, it was found that the amino acid residues interacting with the non-steroidal inhibitors exhibited π-stacking interactions with PHE134, PHE 221, and TRP 224, while the steroidal drug exemestane lacked π-stacking interactions. QSAR studies were performed using the flavonoid compounds, in order to identify the structural functionalities needed to improve the anti-breast cancer activity. Molecular dynamics of the screened hits confirmed the stability of compounds with the target in the binding cavity. Moreover, pharmacophore modelling presented the pharmacophoric features of the selected scaffolds for aromatase inhibitory activity. Conclusion: The results presented 23 hit compounds that can be developed as anti-breast cancer modulating agents in the near future. Additionally, anthraquinone compounds with minor structural modification can also serve to be potential aromatase inhibitors. The in silico protocol utilised can be useful in the drug discovery process for development of new leads from structurally diverse set of natural products that are comparable to the drugs used clinically in breast cancer therapy.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140502171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naeimeh Akbari-Gharalari, Sina Khodakarimi, F. Nezhadshahmohammad, Mohammad Karimipour, Abbas Ebrahimi-Kalan, Jiagian Wu
Introduction: Exosomes, a subset of extracellular vesicles (EVs), are crucial for intercellular communication in various contexts. Despite their small size, they carry diverse cargo, including RNA, proteins, and lipids. Internalization by recipient cells raises concerns about potential disruptions to cellular functions. Notably, the ability of exosomes to traverse the blood-brain barrier (BBB) has significant implications. Methods: To conduct a thorough investigation into the existing academic literature on exosomes within the framework of neuron-glia communication, a comprehensive search strategy was implemented across the PubMed, Google Scholar, and Science Direct databases. Multiple iterations of the keywords "exosome," "neuron-glia communication," and "neurological disorders" were employed to systematically identify relevant publications. Furthermore, an exploration of the Clinicaltrials.gov database was undertaken to identify clinical trials related to cellular signaling, utilizing analogous terminology. Results: Although the immediate practical applications of exosomes are somewhat limited, their potential as carriers of pathogenic attributes offers promising opportunities for the development of precisely targeted therapeutic strategies for neurological disorders. This review presents a comprehensive overview of contemporary insights into the pivotal roles played by exosomes as agents mediating communication between neurons and glial cells within the central nervous system (CNS). Conclusion: By delving into the intricate dynamics of exosomal communication in the CNS, this review contributes to a deeper understanding of the roles of exosomes in both physiological and pathological processes, thereby paving the way for potential therapeutic advancements in the field of neurological disorders.
{"title":"Exosomes in neuron-glia communication: A review on neurodegeneration","authors":"Naeimeh Akbari-Gharalari, Sina Khodakarimi, F. Nezhadshahmohammad, Mohammad Karimipour, Abbas Ebrahimi-Kalan, Jiagian Wu","doi":"10.34172/bi.2023.30153","DOIUrl":"https://doi.org/10.34172/bi.2023.30153","url":null,"abstract":"Introduction: Exosomes, a subset of extracellular vesicles (EVs), are crucial for intercellular communication in various contexts. Despite their small size, they carry diverse cargo, including RNA, proteins, and lipids. Internalization by recipient cells raises concerns about potential disruptions to cellular functions. Notably, the ability of exosomes to traverse the blood-brain barrier (BBB) has significant implications. Methods: To conduct a thorough investigation into the existing academic literature on exosomes within the framework of neuron-glia communication, a comprehensive search strategy was implemented across the PubMed, Google Scholar, and Science Direct databases. Multiple iterations of the keywords \"exosome,\" \"neuron-glia communication,\" and \"neurological disorders\" were employed to systematically identify relevant publications. Furthermore, an exploration of the Clinicaltrials.gov database was undertaken to identify clinical trials related to cellular signaling, utilizing analogous terminology. Results: Although the immediate practical applications of exosomes are somewhat limited, their potential as carriers of pathogenic attributes offers promising opportunities for the development of precisely targeted therapeutic strategies for neurological disorders. This review presents a comprehensive overview of contemporary insights into the pivotal roles played by exosomes as agents mediating communication between neurons and glial cells within the central nervous system (CNS). Conclusion: By delving into the intricate dynamics of exosomal communication in the CNS, this review contributes to a deeper understanding of the roles of exosomes in both physiological and pathological processes, thereby paving the way for potential therapeutic advancements in the field of neurological disorders.","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140512905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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