Pub Date : 2023-01-01Epub Date: 2023-07-22DOI: 10.34172/bi.2023.23809
MohammadAmin Naseri, Seyed Esmail Razavi
Introduction: Vocal folds are responsible for sound generation. In unilateral vocal fold paralysis (UVFP), the recurrent laryngeal nerve, which controls the vocal folds, is paralyzed. Medialization laryngoplasty is a surgery in which an implant is inserted to push the paralyzed vocal fold to the centerline to recover phonation.
Methods: Here, a numerical simulation is used to calculate flow-related parameters to give insight into what happens in healthy and treated(implanted) vocal folds and their enhancement. In the present work, airflow over vocal folds is modeled considering fluid-structure interaction (FSI) and varying inlet pressure. The governing equations are discretized for fluid and solid domains and solved using the Galerkin finite element method. The boundary conditions for healthy and unilaterally paralyzed vocal folds were imposed to agree with real cases behavior.
Results: The results showed the effectiveness of medialization laryngoplasty in treating unilateral vocal fold paralysis concerning healthy vocal folds.
Conclusion: This simulation provided a better insight into treatment results for patient-specific cases.
{"title":"Towards modeling of phonation and its recovery in unilateral vocal fold paralysis by fluid-structure interaction.","authors":"MohammadAmin Naseri, Seyed Esmail Razavi","doi":"10.34172/bi.2023.23809","DOIUrl":"10.34172/bi.2023.23809","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Vocal folds are responsible for sound generation. In unilateral vocal fold paralysis (UVFP), the recurrent laryngeal nerve, which controls the vocal folds, is paralyzed. Medialization laryngoplasty is a surgery in which an implant is inserted to push the paralyzed vocal fold to the centerline to recover phonation.</p><p><strong>Methods: </strong>Here, a numerical simulation is used to calculate flow-related parameters to give insight into what happens in healthy and treated(implanted) vocal folds and their enhancement. In the present work, airflow over vocal folds is modeled considering fluid-structure interaction (FSI) and varying inlet pressure. The governing equations are discretized for fluid and solid domains and solved using the Galerkin finite element method. The boundary conditions for healthy and unilaterally paralyzed vocal folds were imposed to agree with real cases behavior.</p><p><strong>Results: </strong>The results showed the effectiveness of medialization laryngoplasty in treating unilateral vocal fold paralysis concerning healthy vocal folds.</p><p><strong>Conclusion: </strong>This simulation provided a better insight into treatment results for patient-specific cases.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46802740","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}
Pub Date : 2023-01-01Epub Date: 2023-07-15DOI: 10.34172/bi.2023.27717
Sadegh Baradaran Mahdavi, Roya Kelishadi
To Editor, Osteoporosis is a complex non-communicable disease, known as a silent disease, characterized by low bone mass and increased risk of fracture in multiple sites of the body. The worldwide prevalence of osteoporosis is estimated to be 18.3%.1 As a public health concern, osteoporosis is related to remarkable morbidity and mortality rates as well as huge economic costs for the medical system globally. Osteoporosis is thought to have developmental origins in early life.2 Some well-known modifiable or non-modifiable risk factors of osteoporosis consist of age, female gender, inactivity, poor diet, stress, and smoking. A growing body of evidence showed that exposure to different classes of environmental pollutants might be related to low bone mass or increased risk of osteoporosis.3-5 A recent metaanalysis revealed that, unlike mercury, cadmium and lead exposure is associated with an increased risk of osteoporosis or osteopenia (odds ratios = 1.35 and 1.15, respectively).4 Considering air pollution, in line with other research, a recently published study found that in the UK, exposure to particulate matter 2.5 micrometers or less in diameter (PM2.5), nitrogen dioxide (NO2), and nitrogen oxides (NOx) is associated with an increased risk of osteoporosis in 422,955 individuals.6 We had previously summarized the findings on the association of air pollution with bone mass.7 In addition, emerging evidence indicated the detrimental effects of some environmental chemicals, such as perfluoroalkyl substances (PFASs) and phthalates on bone mineral density.5 The underlying pathophysiological mechanisms involved in bone response to environmental pollutants are complex and remain to be determined. Those mechanisms include but are not limited to, induction of pro-inflammation, oxidative stress, and endocrine disruption.4,5 All around the world, humans are exposed to environmental pollutants and are susceptible to their adverse health outcomes. Epigenetics is the study of heritable changes in gene expression resulting from mechanisms other than changes in the DNA sequence and is crucial in determining spatiotemporal patterns of gene expression.8 DNA methylation (DNAm) includes the addition of a methyl group to cytosine residues of CpG dinucleotides. DNAm is often linked to turning off genes. This happens when transcription factors that control gene activity are unable to bind to it or when specific proteins that stop gene activity get attracted to it.9 An accumulating line of evidence supports the pivotal action of epigenetic mechanisms, including DNA methylation, in the influence of environmental chemicals on the disease burden. The effects of epigenetic changes have been linked not only to the prenatal period but also to adulthood. A systematic review proposed a possible role of exposure to cadmium, lead, and persistent organic pollutants (POPs) on DNAm changes.10 Likewise, a literature review of the last 3 years revealed strong evidence between prenatal me
{"title":"DNA methylation as a potential mediator between environmental pollutants and osteoporosis; a current hypothesis.","authors":"Sadegh Baradaran Mahdavi, Roya Kelishadi","doi":"10.34172/bi.2023.27717","DOIUrl":"10.34172/bi.2023.27717","url":null,"abstract":"To Editor, Osteoporosis is a complex non-communicable disease, known as a silent disease, characterized by low bone mass and increased risk of fracture in multiple sites of the body. The worldwide prevalence of osteoporosis is estimated to be 18.3%.1 As a public health concern, osteoporosis is related to remarkable morbidity and mortality rates as well as huge economic costs for the medical system globally. Osteoporosis is thought to have developmental origins in early life.2 Some well-known modifiable or non-modifiable risk factors of osteoporosis consist of age, female gender, inactivity, poor diet, stress, and smoking. A growing body of evidence showed that exposure to different classes of environmental pollutants might be related to low bone mass or increased risk of osteoporosis.3-5 A recent metaanalysis revealed that, unlike mercury, cadmium and lead exposure is associated with an increased risk of osteoporosis or osteopenia (odds ratios = 1.35 and 1.15, respectively).4 Considering air pollution, in line with other research, a recently published study found that in the UK, exposure to particulate matter 2.5 micrometers or less in diameter (PM2.5), nitrogen dioxide (NO2), and nitrogen oxides (NOx) is associated with an increased risk of osteoporosis in 422,955 individuals.6 We had previously summarized the findings on the association of air pollution with bone mass.7 In addition, emerging evidence indicated the detrimental effects of some environmental chemicals, such as perfluoroalkyl substances (PFASs) and phthalates on bone mineral density.5 The underlying pathophysiological mechanisms involved in bone response to environmental pollutants are complex and remain to be determined. Those mechanisms include but are not limited to, induction of pro-inflammation, oxidative stress, and endocrine disruption.4,5 All around the world, humans are exposed to environmental pollutants and are susceptible to their adverse health outcomes. Epigenetics is the study of heritable changes in gene expression resulting from mechanisms other than changes in the DNA sequence and is crucial in determining spatiotemporal patterns of gene expression.8 DNA methylation (DNAm) includes the addition of a methyl group to cytosine residues of CpG dinucleotides. DNAm is often linked to turning off genes. This happens when transcription factors that control gene activity are unable to bind to it or when specific proteins that stop gene activity get attracted to it.9 An accumulating line of evidence supports the pivotal action of epigenetic mechanisms, including DNA methylation, in the influence of environmental chemicals on the disease burden. The effects of epigenetic changes have been linked not only to the prenatal period but also to adulthood. A systematic review proposed a possible role of exposure to cadmium, lead, and persistent organic pollutants (POPs) on DNAm changes.10 Likewise, a literature review of the last 3 years revealed strong evidence between prenatal me","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42002135","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}
Mohammad Ghader Bayazidi, Reza Rahbarghazi, Aysa Rezabakhsh, Jafar Rezaie, Mehdi Hassanpour, Mahdi Ahmadi
Introduction: The current experiment aimed to address the impact of type 2 diabetes mellitus on autophagy status in the rat pulmonary tissue. Methods: In this study, 20 male Wistar rats were randomly allocated into two groups as follows: control and diabetic groups. To induce type 2 diabetes mellitus, rats received a combination of streptozotocin (STZ) and a high-fat diet. After confirmation of diabetic condition, rats were maintained for 8 weeks and euthanized for further analyses. The pathological changes were assessed using H&E staining. We also measured transforming growth factor-β (TGF-β), bronchoalveolar lavage fluid (BALF), and tumor necrosis factor-α (TNF-α) in the lungs using ELISA and real-time PCR analyses, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were monitored in diabetic lungs to assess oxidative status. We also measured the expression of becline-1, LC3, and P62 to show autophagic response under diabetic conditions. Using immunofluorescence staining, protein levels of LC3 was also monitored. Results: H&E staining showed pathological changes in diabetic rats coincided with the increase of TNF-α (~1.4-fold) and TGF-β (~1.3-fold) compared to those in the normal rats (P<0.05). The levels of MDA (5.6 ± 0.4 versus 6.4 ± 0.27 nM/mg protein) were increased while SOD (4.2 ± 0.28 versus 3.8 ± 0.13 U/mL) activity decreased in the diabetic rats (P<0.05). Real-time polymerase chain reaction (PCR) analysis showed the up-regulation of Becline-1 (~1.35-fold) and LC3 (~2-fold) and down-regulation of P62 (~0.8-fold) (P<0.05), showing incomplete autophagic flux. We noted the increase of LC3+ cells in diabetic condition compared to that in the control samples. Conclusion: The prolonged diabetic condition could inhibit the normal activity of autophagy flux, thereby increasing pathological outcomes.
{"title":"Type 2 diabetes mellitus induced autophagic response within pulmonary tissue in the rat model.","authors":"Mohammad Ghader Bayazidi, Reza Rahbarghazi, Aysa Rezabakhsh, Jafar Rezaie, Mehdi Hassanpour, Mahdi Ahmadi","doi":"10.34172/bi.2022.22183","DOIUrl":"https://doi.org/10.34172/bi.2022.22183","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> The current experiment aimed to address the impact of type 2 diabetes mellitus on autophagy status in the rat pulmonary tissue. <i><b>Methods:</b> </i> In this study, 20 male Wistar rats were randomly allocated into two groups as follows: control and diabetic groups. To induce type 2 diabetes mellitus, rats received a combination of streptozotocin (STZ) and a high-fat diet. After confirmation of diabetic condition, rats were maintained for 8 weeks and euthanized for further analyses. The pathological changes were assessed using H&E staining. We also measured transforming growth factor-β (TGF-β), bronchoalveolar lavage fluid (BALF), and tumor necrosis factor-α (TNF-α) in the lungs using ELISA and real-time PCR analyses, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were monitored in diabetic lungs to assess oxidative status. We also measured the expression of becline-1, LC3, and P62 to show autophagic response under diabetic conditions. Using immunofluorescence staining, protein levels of LC3 was also monitored. <i><b>Results:</b> </i> H&E staining showed pathological changes in diabetic rats coincided with the increase of TNF-α (~1.4-fold) and TGF-β (~1.3-fold) compared to those in the normal rats (<i>P</i><0.05). The levels of MDA (5.6 ± 0.4 versus 6.4 ± 0.27 nM/mg protein) were increased while SOD (4.2 ± 0.28 versus 3.8 ± 0.13 U/mL) activity decreased in the diabetic rats (<i>P</i><0.05). Real-time polymerase chain reaction (PCR) analysis showed the up-regulation of Becline-1 (~1.35-fold) and LC3 (~2-fold) and down-regulation of P62 (~0.8-fold) (<i>P</i><0.05), showing incomplete autophagic flux. We noted the increase of LC3<sup>+</sup> cells in diabetic condition compared to that in the control samples. <i><b>Conclusion:</b> </i> The prolonged diabetic condition could inhibit the normal activity of autophagy flux, thereby increasing pathological outcomes.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/0b/bi-13-43.PMC9923816.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329403","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}
Tina Sepasi, Farhad Bani, Reza Rahbarghazi, Abbas Ebrahimi-Kalan, Mohammad-Reza Sadeghi, Seyedeh Zahra Alamolhoda, Amir Zarebkohan, Tahereh Ghadiri, Huile Gao
Introduction: Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). Methods: Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy. Results: Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. Conclusion: Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).
{"title":"Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles.","authors":"Tina Sepasi, Farhad Bani, Reza Rahbarghazi, Abbas Ebrahimi-Kalan, Mohammad-Reza Sadeghi, Seyedeh Zahra Alamolhoda, Amir Zarebkohan, Tahereh Ghadiri, Huile Gao","doi":"10.34172/bi.2022.23876","DOIUrl":"https://doi.org/10.34172/bi.2022.23876","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). <i><b>Methods:</b></i> Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For <i>in vitro</i> assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using <i>in vivo</i> imaging and fluorescent microscopy. <i><b>Results:</b></i> Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. <i>In vivo</i> imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. <i><b>Conclusion:</b></i> Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/3e/bi-13-133.PMC10182443.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485466","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}
Introduction: Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells.
Methods: We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel.
Results: Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells.
Conclusion: The production of oocyte-like cells using 3D alginate hydrogel may be viable in vitro approach for replacing gonad tissues and cells.
人子宫内膜间充质干细胞(hEnMSCs)是一种丰富的间充质干细胞(MSCs)来源,具有多谱系分化潜力,使其成为再生医学中一个有趣的工具,特别是用于治疗生殖和不孕症问题。生殖系细胞来源的干细胞分化的具体过程尚不清楚,目的是研究新的方法来实现有效的分化方法,产生足够的和功能齐全的人类配子细胞。方法:调整维甲酸(RA)的最佳浓度,以增强2D细胞培养7天后生殖细胞源性hEnSCs的生成。随后,我们开发了一种合适的卵母细胞样细胞诱导培养基,包括RA和骨形态发生蛋白4 (bone morphogenetic protein 4, BMP4),并利用海藻酸盐水凝胶包裹细胞,在二维和三维细胞培养基中研究了它们对卵母细胞样细胞分化的影响。结果:显微镜分析、实时PCR和免疫荧光检测结果显示,10µM RA浓度是诱导7天后胚样细胞的最佳剂量。通过流变学分析和扫描电镜对海藻酸盐水凝胶的结构特征和完整性进行了研究。我们还证明了包被细胞的活力和粘附在制造的水凝胶。我们提出,在海藻酸盐水凝胶中的3D细胞培养中,含有10µM RA和50 ng/mL BMP4的诱导培养基可以促进hEnSC向卵母细胞样细胞的分化。结论:三维海藻酸盐水凝胶制备卵母细胞样细胞是体外替代性腺组织和细胞的可行方法。
{"title":"Differentiation of human endometrial stem cells encapsulated in alginate hydrogel into oocyte-like cells.","authors":"Diba Ghasemi, Somayeh Ebrahimi-Barough, Mohammad Hossein Nekoofar, Abdolreza Mohamadnia, Nasrin Lotfibakhshaiesh, Naghmeh Bahrami, Roya Karimi, Vajihe Taghdiri Nooshabadi, Mahmoud Azami, Elham Hasanzadeh, Jafar Ai","doi":"10.34172/bi.2022.23960","DOIUrl":"https://doi.org/10.34172/bi.2022.23960","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells.</p><p><strong>Methods: </strong>We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel.</p><p><strong>Results: </strong>Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells.</p><p><strong>Conclusion: </strong>The production of oocyte-like cells using 3D alginate hydrogel may be viable <i>in vitro</i> approach for replacing gonad tissues and cells.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/10/bi-13-229.PMC10329755.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814704","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}
Introduction: The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway.
Methods: Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis.
Results: In vitro results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed.
Conclusion: Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.
{"title":"Combination of pioglitazone and dendritic cell to optimize efficacy of immune cell therapy in CT26 tumor models.","authors":"Samaneh Tokhanbigli, Helia Alavifard, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Kaveh Baghaei","doi":"10.34172/bi.2022.24209","DOIUrl":"https://doi.org/10.34172/bi.2022.24209","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway.</p><p><strong>Methods: </strong>Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis.</p><p><strong>Results: </strong><i>In vitro</i> results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed.</p><p><strong>Conclusion: </strong>Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/dc/bi-13-333.PMC10460770.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117769","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}
Yuri Yu Shchegolev, Danila V Sorokin, Alexander M Scherbakov, Olga E Andreeva, Diana I Salnikova, Ekaterina I Mikhaevich, Margarita V Gudkova, Mikhail A Krasil'nikov
Introduction: Resistance to chemotherapy and/or irradiation remains one of the key features of malignant tumors, which largely limits the efficiency of antitumor therapy. In this work, we studied the progression mechanism of breast cancer cell resistance to target drugs, including mTOR blockers, and in particular, we studied the exosome function in intercellular resistance transfer.
Methods: The cell viability was assessed by the MTT assay, exosomes were purified by successive centrifugations, immunoblotting was used to evaluate protein expression, AP-1 activity was analyzed using reporter assay.
Results: In experiments on the MCF-7 cell line (breast cancer) and the MCF-7/Rap subline that is resistant to rapamycin, the capability of resistant cell exosomes to trigger a similar rapamycin resistance in the parent MCF-7 cells was demonstrated. Exosome-induced resistance reproduces the changes revealed in MCF-7/Rap resistant cells, including the activation of ERK/AP-1 signaling, and it remains for a long time, for at least several months, after exosome withdrawal. We have shown that both the MCF-7 subline resistant to rapamycin and cells having exosome-triggered resistance demonstrate a stable decrease in the expression of DNMT3A, the key enzyme responsible for DNA methylation. Knockdown of DNMT3A in MCF-7 cells by siRNA leads to partial cell resistance to rapamycin; thus, the DNMT3A suppression is regarded as one of the necessary elements for the development of acquired rapamycin resistance.
Conclusion: We propose that DNA demethylation followed by increased expression of key genes may be one of the factors responsible for the progression and maintenance of the resistant cell phenotype that includes exosome-induced resistance.
{"title":"Exosomes are involved in the intercellular transfer of rapamycin resistance in the breast cancer cells.","authors":"Yuri Yu Shchegolev, Danila V Sorokin, Alexander M Scherbakov, Olga E Andreeva, Diana I Salnikova, Ekaterina I Mikhaevich, Margarita V Gudkova, Mikhail A Krasil'nikov","doi":"10.34172/bi.2023.27490","DOIUrl":"https://doi.org/10.34172/bi.2023.27490","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Resistance to chemotherapy and/or irradiation remains one of the key features of malignant tumors, which largely limits the efficiency of antitumor therapy. In this work, we studied the progression mechanism of breast cancer cell resistance to target drugs, including mTOR blockers, and in particular, we studied the exosome function in intercellular resistance transfer.</p><p><strong>Methods: </strong>The cell viability was assessed by the MTT assay, exosomes were purified by successive centrifugations, immunoblotting was used to evaluate protein expression, AP-1 activity was analyzed using reporter assay.</p><p><strong>Results: </strong>In experiments on the MCF-7 cell line (breast cancer) and the MCF-7/Rap subline that is resistant to rapamycin, the capability of resistant cell exosomes to trigger a similar rapamycin resistance in the parent MCF-7 cells was demonstrated. Exosome-induced resistance reproduces the changes revealed in MCF-7/Rap resistant cells, including the activation of ERK/AP-1 signaling, and it remains for a long time, for at least several months, after exosome withdrawal. We have shown that both the MCF-7 subline resistant to rapamycin and cells having exosome-triggered resistance demonstrate a stable decrease in the expression of DNMT3A, the key enzyme responsible for DNA methylation. Knockdown of DNMT3A in MCF-7 cells by siRNA leads to partial cell resistance to rapamycin; thus, the DNMT3A suppression is regarded as one of the necessary elements for the development of acquired rapamycin resistance.</p><p><strong>Conclusion: </strong>We propose that DNA demethylation followed by increased expression of key genes may be one of the factors responsible for the progression and maintenance of the resistant cell phenotype that includes exosome-induced resistance.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/c1/bi-13-313.PMC10460766.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175897","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}
Seyedeh-Sara Hashemi, Ali Akbar Mohammadi, Seyedeh-Somayeh Rajabi, Parisa Sanati, Alireza Rafati, Mehdi Kian, Zahra Zarei
Introduction: Recently, the application of nanofibrous mats for dressing skin wounds has received great attention. In this study, we aimed to fabricate and characterize an electrospun nanofibrous mat containing polycaprolactone (PCL), chitosan (CTS), and propolis for use as a tissue-engineered skin substitute.
Methods: Raw propolis was extracted, and its phenolic and flavonoid contents were measured. The physiochemical and biological properties of the fabricated mats, including PCL, PCL/CTS, and PCL/CTS/Propolis were evaluated by scanning electron microscopy (SEM), atomic force microscopy (AFM), mechanical analysis, swelling and degradation behaviors, contact angle measurement, cell attachment, DAPI staining, and MTT assay. On the other hand, the drug release pattern of propolis from the PCL/CTS/Propolis scaffold was determined. A deep second-degree burn wound model was induced in rats to investigate wound healing using macroscopical and histopathological evaluations.
Results: The results revealed that the propolis extract contained high amounts of phenolic and flavonoid compounds. The fabricated scaffold had suitable physicochemical and mechanical properties. Uniform, bead-free, and well-branched fibers were observed in SEM images of mats. AFM analysis indicated that the addition of CTS and propolis to PCL elevated the surface roughness. MTT results revealed that the electrospun PCL/CTS/Propolis mat was biocompatible. The presence of fibroblast cells on the PCL/CTS/Propolis mats was confirmed by DAPI staining and SEM images. Also, propolis was sustainably released from the PCL/CTS/Propolis mat. The animal study revealed that addition of propolis significantly improved wound healing.
Conclusion: The nanofibrous PCL/CTS/Propolis mat can be applied as a tissue-engineered skin substitute for healing cutaneous wounds, such as burn wounds.
{"title":"Preparation and evaluation of a polycaprolactone/chitosan/propolis fibrous nanocomposite scaffold as a tissue engineering skin substitute.","authors":"Seyedeh-Sara Hashemi, Ali Akbar Mohammadi, Seyedeh-Somayeh Rajabi, Parisa Sanati, Alireza Rafati, Mehdi Kian, Zahra Zarei","doi":"10.34172/bi.2023.26317","DOIUrl":"https://doi.org/10.34172/bi.2023.26317","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Recently, the application of nanofibrous mats for dressing skin wounds has received great attention. In this study, we aimed to fabricate and characterize an electrospun nanofibrous mat containing polycaprolactone (PCL), chitosan (CTS), and propolis for use as a tissue-engineered skin substitute.</p><p><strong>Methods: </strong>Raw propolis was extracted, and its phenolic and flavonoid contents were measured. The physiochemical and biological properties of the fabricated mats, including PCL, PCL/CTS, and PCL/CTS/Propolis were evaluated by scanning electron microscopy (SEM), atomic force microscopy (AFM), mechanical analysis, swelling and degradation behaviors, contact angle measurement, cell attachment, DAPI staining, and MTT assay. On the other hand, the drug release pattern of propolis from the PCL/CTS/Propolis scaffold was determined. A deep second-degree burn wound model was induced in rats to investigate wound healing using macroscopical and histopathological evaluations.</p><p><strong>Results: </strong>The results revealed that the propolis extract contained high amounts of phenolic and flavonoid compounds. The fabricated scaffold had suitable physicochemical and mechanical properties. Uniform, bead-free, and well-branched fibers were observed in SEM images of mats. AFM analysis indicated that the addition of CTS and propolis to PCL elevated the surface roughness. MTT results revealed that the electrospun PCL/CTS/Propolis mat was biocompatible. The presence of fibroblast cells on the PCL/CTS/Propolis mats was confirmed by DAPI staining and SEM images. Also, propolis was sustainably released from the PCL/CTS/Propolis mat. The animal study revealed that addition of propolis significantly improved wound healing.</p><p><strong>Conclusion: </strong>The nanofibrous PCL/CTS/Propolis mat can be applied as a tissue-engineered skin substitute for healing cutaneous wounds, such as burn wounds.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/78/bi-13-275.PMC10460768.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175902","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}
Introduction: Nisin is a bacteriocin produced by Streptococcus and Lactococcus species and has antimicrobial activity against other bacteria. Nisin omits the need to use chemical preservatives in food due to its biological preserving properties.
Methods: In the present in vitro study, we investigated nisin interaction with bovine serum albumin (BSA) using fluorescence spectroscopy and surface plasmon resonance (SPR) analysis to obtain information about the mechanisms of BSA complex formation with nisin.
Results: The BSA fluorescence intensity values gradually diminished with rising nisin concentration. The BSA fluorescence quenching analysis indicated that a combined quenching mechanism plays the main role. Finally, the Kb values were reduced with increasing temperature, which is demonstrative of nisin-BSA complex stability decrease at high temperatures. The negative values of ΔH° and ΔS° showed that hydrogen bonds and van der Waals forces are the foremost binding force between BSA and nisin. Meanwhile, the negative values of ΔG° demonstrated the exothermic and random nature of the reaction process. The results of the SPR verified the gained results through the fluorescence spectroscopy investigation, which denoted that the BSA affinity to nisin diminished upon increasing temperature.
Conclusion: Overall, fluorescence spectroscopy and SPR results showed that the BSA interaction with nisin decreased with rising temperatures.
{"title":"Spectroscopic aspects on the interaction of nisin with serum albumin: thermodynamic and kinetic studies.","authors":"Maryam Azimirad, Fatemeh Javaheri-Ghezeldizaj, Jafar Soleymani, Jafar Ezzati Nazhad Dolatabadi, Mohammadali Torbati","doi":"10.34172/bi.2023.27754","DOIUrl":"10.34172/bi.2023.27754","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Nisin is a bacteriocin produced by <i>Streptococcus</i> and <i>Lactococcus</i> species and has antimicrobial activity against other bacteria. Nisin omits the need to use chemical preservatives in food due to its biological preserving properties.</p><p><strong>Methods: </strong>In the present <i>in vitro</i> study, we investigated nisin interaction with bovine serum albumin (BSA) using fluorescence spectroscopy and surface plasmon resonance (SPR) analysis to obtain information about the mechanisms of BSA complex formation with nisin.</p><p><strong>Results: </strong>The BSA fluorescence intensity values gradually diminished with rising nisin concentration. The BSA fluorescence quenching analysis indicated that a combined quenching mechanism plays the main role. Finally, the K<sub>b</sub> values were reduced with increasing temperature, which is demonstrative of nisin-BSA complex stability decrease at high temperatures. The negative values of ΔH° and ΔS° showed that hydrogen bonds and van der Waals forces are the foremost binding force between BSA and nisin. Meanwhile, the negative values of ΔG° demonstrated the exothermic and random nature of the reaction process. The results of the SPR verified the gained results through the fluorescence spectroscopy investigation, which denoted that the BSA affinity to nisin diminished upon increasing temperature.</p><p><strong>Conclusion: </strong>Overall, fluorescence spectroscopy and SPR results showed that the BSA interaction with nisin decreased with rising temperatures.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45214066","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}
Introduction: Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as "phytosome", to improve silymarin bioavailability and increase its efficacy.
Methods: Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, in vitro toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. In vivo experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes.
Results: Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations.
Conclusion: Silymarin phytosomal NPs can be used as an efficient treatment for ALD.
{"title":"Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.","authors":"Arezoo Gohari Mahmoudabad, Fatemeh Gheybi, Mohsen Mehrabi, Alireza Masoudi, Zeinab Mobasher, Hamid Vahedi, Anneh Mohammad Gharravi, Fatemeh Sadat Bitaraf, Seyed Mahdi Rezayat Sorkhabadi","doi":"10.34172/bi.2023.24128","DOIUrl":"https://doi.org/10.34172/bi.2023.24128","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Silymarin proved to be a beneficial herbal medicine against many hepatic disorders such as alcoholic liver disease (ALD). However, its application is restricted due to its low bioavailability and consequently decreased efficacy. We herein used a nano-based approach known as \"phytosome\", to improve silymarin bioavailability and increase its efficacy.</p><p><strong>Methods: </strong>Phytosome nanoparticles (NPs) were synthesized using thin film hydration method. NPs size, electrical charge, morphology, stability, molecular interaction, entrapment efficiency (EE %) and loading capacity (LC %) were determined. Moreover, <i>in vitro</i> toxicity of NPs was investigated on mesenchymal stem cells (MSCs) viability using MTT assay. <i>In vivo</i> experiments were performed using 24 adult rats that were divided into four groups including control, ethanol (EtOH) treatment, silymarin/EtOH treatment and silymarin phytosome/EtOH, with 6 mice in each group. Experimental groups were given 40% EtOH, silymarin (50 mg/kg) and silymarin phytosome (200 mg/kg) through the gastric gavage once a day for 3 weeks. Biochemical parameters, containing ALP, ALT, AST, GGT, GPx and MDA were measured before and after experiment to investigate the protective effect of silymarin and its phytosomal form. And histopathological examination was done to evaluate pathological changes.</p><p><strong>Results: </strong>Silymarin phytosome NPs with the mean size of 100 nm were produced and were well tolerated in cell culture. These NPs showed a considerable protective effect against ALD through inverting the biochemical parameters (ALP, ALT, AST, GGT, GPx) and histopathological alterations.</p><p><strong>Conclusion: </strong>Silymarin phytosomal NPs can be used as an efficient treatment for ALD.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/b8/bi-13-301.PMC10460772.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117768","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}