Introduction: Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear.
Methods: LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro.
Results: AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects.
Conclusion: Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.
{"title":"Artesunate reduces sepsis-mediated acute lung injury in a SIRT1-dependent manner.","authors":"Zhaohui Liu, Yanli Meng, Yu Miao, Lili Yu, Qiannan Yu","doi":"10.34172/bi.2023.23585","DOIUrl":"https://doi.org/10.34172/bi.2023.23585","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear.</p><p><strong>Methods: </strong>LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro.</p><p><strong>Results: </strong>AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects.</p><p><strong>Conclusion: </strong>Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"219-228"},"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/52/7d/bi-13-219.PMC10329753.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814700","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 CSF1R gene encodes the receptor for colony-stimulating factor-1, the macrophage, and monocyte-specific growth factor. Mutations in this gene cause hereditary diffuse leukoencephalopathy with spheroids (HDLS) with autosomal dominant inheritance and BANDDOS (Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis) with autosomal recessive inheritance.
Methods: Targeted gene sequencing was performed on the genomic DNA samples of the deceased patient and a fetus along with ten healthy members of his family to identify the disease-causing mutation. Bioinformatics tools were used to study the mutation effect on protein function and structure. To predict the effect of the mutation on the protein, various bioinformatics tools were applied.
Results: A novel homozygous variant was identified in the gene CSF1R, c.2498C>T; p.T833M in exon 19, in the index patient and the fetus. Furthermore, some family members were heterozygous for this variant, while they had not any symptoms of the disease. In silico analysis indicated this variant has a detrimental effect on CSF1R. It is conserved among humans and other similar species. The variant is located within the functionally essential PTK domain of the receptor. However, no structural damage was introduced by this substitution.
Conclusion: In conclusion, regarding the inheritance pattern in the family and clinical manifestations in the index patient, we propose that the mentioned variant in the CSF1R gene may cause BANDDOS.
{"title":"Homozygous mutation in <i>CSF1R</i> causes brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS).","authors":"Hossein Daghagh, Haniyeh Rahbar Kafshboran, Yousef Daneshmandpour, Maryam Nasiri Aghdam, Shahrzad Talebian, Jafar Nouri Nojadeh, Hamid Hamzeiy, Saskia Biskup, Ebrahim Sakhinia","doi":"10.34172/bi.2022.23528","DOIUrl":"https://doi.org/10.34172/bi.2022.23528","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>The <i>CSF1R</i> gene encodes the receptor for colony-stimulating factor-1, the macrophage, and monocyte-specific growth factor. Mutations in this gene cause hereditary diffuse leukoencephalopathy with spheroids (HDLS) with autosomal dominant inheritance and BANDDOS (Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis) with autosomal recessive inheritance.</p><p><strong>Methods: </strong>Targeted gene sequencing was performed on the genomic DNA samples of the deceased patient and a fetus along with ten healthy members of his family to identify the disease-causing mutation. Bioinformatics tools were used to study the mutation effect on protein function and structure. To predict the effect of the mutation on the protein, various bioinformatics tools were applied.</p><p><strong>Results: </strong>A novel homozygous variant was identified in the gene <i>CSF1R</i>, c.2498C>T; p.T833M in exon 19, in the index patient and the fetus. Furthermore, some family members were heterozygous for this variant, while they had not any symptoms of the disease. In silico analysis indicated this variant has a detrimental effect on CSF1R. It is conserved among humans and other similar species. The variant is located within the functionally essential PTK domain of the receptor. However, no structural damage was introduced by this substitution.</p><p><strong>Conclusion: </strong>In conclusion, regarding the inheritance pattern in the family and clinical manifestations in the index patient, we propose that the mentioned variant in the <i>CSF1R</i> gene may cause BANDDOS.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"183-190"},"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/7f/06/bi-13-183.PMC10329754.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9814702","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}
The delivery of chemotherapies to brain tumors faces the difficult task of crossing the blood-brain barrier (BBB).1-4 The brain capillary endothelial cells (BCECs) along with other cell lines, such as astrocytes and pericytes, form the BBB. This highly selective semipermeable barrier separates the blood from the brain parenchyma. The BBB controls the movement of drug molecules in a selective manner5 and maintains central nervous system (CNS) homeostasis. Depending on the properties of drugs such as their hydrophilic-lipophilic balance (HLB), some can cross the BBB through passive diffusion.6 However, this approach alone has not led to successful drug developments due to low net diffusion rates and systemic toxicity. Although the use of nanomedicine has been proposed to overcome these drawbacks, many recent studies still rely on the so-called 'enhanced permeability and retention (EPR)' effect though there is a realization in the field of drug delivery that EPR effect may not be sufficient for successful drug delivery to brain tumors. Since, compared to many other solid tumors, brain tumors pose additional challenges such as more restrictive blood-tumor barrier as well as the well-developed lymphatic drainage, the selection of functional moieties on the nanocarriers under consideration must be carried out with care to propose better solutions to this challenge.
{"title":"Dual-targeting of brain tumors with nanovesicles.","authors":"Nazanin Kianinejad, Young Min Kwon","doi":"10.34172/bi.2022.26321","DOIUrl":"https://doi.org/10.34172/bi.2022.26321","url":null,"abstract":"<p><p>The delivery of chemotherapies to brain tumors faces the difficult task of crossing the blood-brain barrier (BBB).<sup>1-4</sup> The brain capillary endothelial cells (BCECs) along with other cell lines, such as astrocytes and pericytes, form the BBB. This highly selective semipermeable barrier separates the blood from the brain parenchyma. The BBB controls the movement of drug molecules in a selective manner<sup>5</sup> and maintains central nervous system (CNS) homeostasis. Depending on the properties of drugs such as their hydrophilic-lipophilic balance (HLB), some can cross the BBB through passive diffusion.<sup>6</sup> However, this approach alone has not led to successful drug developments due to low net diffusion rates and systemic toxicity. Although the use of nanomedicine has been proposed to overcome these drawbacks, many recent studies still rely on the so-called 'enhanced permeability and retention (EPR)' effect though there is a realization in the field of drug delivery that EPR effect may not be sufficient for successful drug delivery to brain tumors. Since, compared to many other solid tumors, brain tumors pose additional challenges such as more restrictive blood-tumor barrier as well as the well-developed lymphatic drainage, the selection of functional moieties on the nanocarriers under consideration must be carried out with care to propose better solutions to this challenge.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"1-3"},"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/df/5e/bi-13-1.PMC9923813.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767207","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: Here, the interaction behavior between propyl acridones (PA) and calf thymus DNA (ct-DNA) has been investigated to attain the features of the binding behavior of PA with ct-DNA, which includes specific binding sites, modes, and constants. Furthermore, the effects of PA on the conformation of ct-DNA seem to be quite significant for comprehending the medicine's mechanism of action and pharmacokinetics. Methods: The project was accomplished through means of absorbance studies, fluorescence spectroscopy, circular dichroism, viscosity measurement, thermal melting, and molecular modeling techniques. Results: The intercalation of PA has been suggested by fluorescence quenching and viscosity measurements results while the thermal melting and circular dichroism studies have confirmed the thermal stabilization and conformational changes that seem to be associated with the binding. The binding constants of ct-DNA-PA complex, in the absence and presence of EMF, have been evaluated to be 6.19 × 104 M-1 and 2.95 × 104 M-1 at 298 K, respectively. In the absence of EMF, the ∆H0 and ∆S0 values that occur in the interaction process of PA with ct-DNA have been measured to be -11.81 kJ.mol-1 and 51.01 J.mol-1K-1, while in the presence of EMF they were observed to be -23.34 kJ.mol-1 and 7.49 J.mol-1K-1, respectively. These numbers indicate the involvement of multiple non-covalent interactions in the binding procedure. In a parallel study, DNA-PA interactions have been monitored by molecular dynamics simulations; their results have demonstrated DNA stability with increasing concentrations of PA, as well as calculated bindings of theoretical ΔG0. Conclusion: The complex formation between PA and ct-DNA has been investigated in the presence and absence of EMF through the multi spectroscopic techniques and MD simulation. These findings have been observed to be parallel to the results of KI and NaCl quenching studies, as well as the competitive displacement with EB and AO. According to thermodynamic parameters, electrostatic interactions stand as the main energy that binds PA to ct-DNA. Regarding the cases that involve the Tm of ct-DNA, EMF has proved to increase the stability of binding between PA and ct-DNA.
{"title":"Multi spectroscopic and molecular simulation studies of propyl acridone binding to calf thymus DNA in the presence of electromagnetic force.","authors":"Atena Sharifi-Rad, Zeinab Amiri-Tehranizadeh, Atiye Talebi, Niknaz Nosrati, Morvarid Medalian, Mahtab Pejhan, Nazanin Hamzkanloo, Mohammad Reza Saberi, Parisa Mokaberi, Jamshidkhan Chamani","doi":"10.34172/bi.2022.23592","DOIUrl":"https://doi.org/10.34172/bi.2022.23592","url":null,"abstract":"<p><p><i><b>Introduction:</b> </i> Here, the interaction behavior between propyl acridones (PA) and calf thymus DNA (ct-DNA) has been investigated to attain the features of the binding behavior of PA with ct-DNA, which includes specific binding sites, modes, and constants. Furthermore, the effects of PA on the conformation of ct-DNA seem to be quite significant for comprehending the medicine's mechanism of action and pharmacokinetics. <i><b>Methods:</b> </i> The project was accomplished through means of absorbance studies, fluorescence spectroscopy, circular dichroism, viscosity measurement, thermal melting, and molecular modeling techniques. <i><b>Results:</b> </i> The intercalation of PA has been suggested by fluorescence quenching and viscosity measurements results while the thermal melting and circular dichroism studies have confirmed the thermal stabilization and conformational changes that seem to be associated with the binding. The binding constants of ct-DNA-PA complex, in the absence and presence of EMF, have been evaluated to be 6.19 × 10<sup>4</sup> M<sup>-1</sup> and 2.95 × 10<sup>4</sup> M<sup>-1</sup> at 298 K, respectively. In the absence of EMF, the ∆H<sup>0</sup> and ∆S<sup>0</sup> values that occur in the interaction process of PA with ct-DNA have been measured to be -11.81 kJ.mol<sup>-1</sup> and 51.01 J.mol<sup>-1</sup>K<sup>-1</sup>, while in the presence of EMF they were observed to be -23.34 kJ.mol<sup>-1</sup> and 7.49 J.mol<sup>-1</sup>K<sup>-1</sup>, respectively. These numbers indicate the involvement of multiple non-covalent interactions in the binding procedure. In a parallel study, DNA-PA interactions have been monitored by molecular dynamics simulations; their results have demonstrated DNA stability with increasing concentrations of PA, as well as calculated bindings of theoretical ΔG<sup>0</sup>. <i><b>Conclusion:</b> </i> The complex formation between PA and ct-DNA has been investigated in the presence and absence of EMF through the multi spectroscopic techniques and MD simulation. These findings have been observed to be parallel to the results of KI and NaCl quenching studies, as well as the competitive displacement with EB and AO. According to thermodynamic parameters, electrostatic interactions stand as the main energy that binds PA to ct-DNA. Regarding the cases that involve the T<sub>m</sub> of ct-DNA, EMF has proved to increase the stability of binding between PA and ct-DNA.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"5-16"},"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/c3/bi-13-5.PMC9923809.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9314947","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: Treatment of critical-sized bone defects is challenging. Tissue engineering as a state-of-the-art method has been concerned with treating these non-self-healing bone defects. Here, we studied the potentials of new three-dimensional nanofibrous scaffolds (3DNS) with and without human adipose mesenchymal stem cells (ADSCs) for reconstructing rat critical-sized calvarial defects (CSCD). Methods: Scaffolds were made from 1- polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA) (PTFE/ PVA group), and 2- PTFE, PVA, and graphene oxide (GO) nanoparticle (PTFE/ PVA/GO group) and seeded by ADSCs and incubated in osteogenic media (OM). The expression of key osteogenic proteins including Runt-related transcription factor 2 (Runx2), collagen type Iα (COL Iα), osteocalcin (OCN), and osteonectin (ON) at days 14 and 21 of culture were evaluated by western blot and immunocytochemistry methods. Next, 40 selected rats were assigned to five groups (n=8) to create CSCD which will be filled by scaffolds or cell-containing scaffolds. The groups were denominated as the following order: Control (empty defects), PTFE/PVA (PTFE/PVA scaffolds implant), PTFE/PVA/GO (PTFE/PVA/GO scaffolds implant), PTFE/PVA/Cell group (PTFE/PVA scaffolds containing ADSCs implant), and PTFE/PVA/GO/Cell group (PTFE/PVA/GO scaffolds containing ADSCs implant). Six and 12 weeks after implantation, the animals were sacrificed and bone regeneration was evaluated using computerized tomography (CT), and hematoxylin-eosin (H&E) staining. Results: Based on the in-vitro study, expression of bone-related proteins in ADSCs seeded on PTFE/PVA/GO scaffolds were significantly higher than PTFE/PVA scaffolds and TCPS (P<0.05). Based on the in-vivo study, bone regeneration in CSCD were filled with PTFE/PVA/GO scaffolds containing ADSCs were significantly higher than PTFE/PVA scaffolds containing ADSCs (P<0.05). CSCD filled with cell-seeded scaffolds showed higher bone regeneration in comparison with CSCD filled with scaffolds only (P<0.05). Conclusion: The data provided evidence showing new freeze-dried nanofibrous scaffolds formed from hydrophobic (PTFE) and hydrophilic (PVA) polymers with and without GO provide a suitable environment for ADSCs due to the expression of bone-related proteins. ADSCs and GO in the implanted scaffolds had a distinct effect on the bone regeneration process in this in-vivo study.
{"title":"Repairing rat calvarial defects by adipose mesenchymal stem cells and novel freeze-dried three-dimensional nanofibrous scaffolds.","authors":"Maryam Sadat Khoramgah, Hossein Ghanbarian, Javad Ranjbari, Nilufar Ebrahimi, Fatemeh Sadat Tabatabaei Mirakabad, Navid Ahmady Roozbahany, Hojjat Allah Abbaszadeh, Simzar Hosseinzadeh","doi":"10.34172/bi.2021.23711","DOIUrl":"https://doi.org/10.34172/bi.2021.23711","url":null,"abstract":"<p><p><b><i>Introduction:</i> </b> Treatment of critical-sized bone defects is challenging. Tissue engineering as a state-of-the-art method has been concerned with treating these non-self-healing bone defects. Here, we studied the potentials of new three-dimensional nanofibrous scaffolds (3DNS) with and without human adipose mesenchymal stem cells (ADSCs) for reconstructing rat critical-sized calvarial defects (CSCD). <i><b>Methods:</b> </i> Scaffolds were made from 1- polytetrafluoroethylene (PTFE), and polyvinyl alcohol (PVA) (PTFE/ PVA group), and 2- PTFE, PVA, and graphene oxide (GO) nanoparticle (PTFE/ PVA/GO group) and seeded by ADSCs and incubated in osteogenic media (OM). The expression of key osteogenic proteins including Runt-related transcription factor 2 (Runx2), collagen type Iα (COL Iα), osteocalcin (OCN), and osteonectin (ON) at days 14 and 21 of culture were evaluated by western blot and immunocytochemistry methods. Next, 40 selected rats were assigned to five groups (n=8) to create CSCD which will be filled by scaffolds or cell-containing scaffolds. The groups were denominated as the following order: Control (empty defects), PTFE/PVA (PTFE/PVA scaffolds implant), PTFE/PVA/GO (PTFE/PVA/GO scaffolds implant), PTFE/PVA/Cell group (PTFE/PVA scaffolds containing ADSCs implant), and PTFE/PVA/GO/Cell group (PTFE/PVA/GO scaffolds containing ADSCs implant). Six and 12 weeks after implantation, the animals were sacrificed and bone regeneration was evaluated using computerized tomography (CT), and hematoxylin-eosin (H&E) staining. <i><b>Results:</b> </i> Based on the in-vitro study, expression of bone-related proteins in ADSCs seeded on PTFE/PVA/GO scaffolds were significantly higher than PTFE/PVA scaffolds and TCPS (<i>P</i><0.05). Based on the in-vivo study, bone regeneration in CSCD were filled with PTFE/PVA/GO scaffolds containing ADSCs were significantly higher than PTFE/PVA scaffolds containing ADSCs (<i>P</i><0.05). CSCD filled with cell-seeded scaffolds showed higher bone regeneration in comparison with CSCD filled with scaffolds only (<i>P</i><0.05). <i><b>Conclusion:</b> </i> The data provided evidence showing new freeze-dried nanofibrous scaffolds formed from hydrophobic (PTFE) and hydrophilic (PVA) polymers with and without GO provide a suitable environment for ADSCs due to the expression of bone-related proteins. ADSCs and GO in the implanted scaffolds had a distinct effect on the bone regeneration process in this in-vivo study.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 1","pages":"31-42"},"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/52/1c/bi-13-31.PMC9923815.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329402","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: 2023-03-01DOI: 10.34172/bi.2023.23515
Raghdah S Bawadud, Mayson H Alkhatib
Introduction: The approach for drug delivery has impressively developed with the emergence of nanosuspension, particularly the targeted nanoemulsions (NEs). It can potentially improve the bioavailability of drugs, enhancing their therapeutic efficiency. This study aims to examine the potential role of NE as a delivery system for the combination of docetaxel (DTX), a microtubule-targeting agent, and thymoquinone (TQ) in the treatment of human ductal carcinoma cells T47D. Methods: NEs were synthesized by ultra-sonication and characterized physically by dynamic light scattering (DLS). A sulforhodamine B assay was performed to evaluate cytotoxicity, and a flow cytometry analysis for cell cycle, apoptosis, autophagy, and cancer stem cell evaluations. A quantitative polymerase chain reaction further assessed the epithelial-mesenchymal transition gene expirations of SNAIL-1, ZEB-1, and TWIST-1. Results: The optimal sizes of blank-NEs and NE-DTX+TQ were found at 117.3 ± 8 nm and 373 ± 6.8 nm, respectively. The synergistic effect of the NE-DTX+TQ formulation significantly inhibited the in vitro proliferation of T47D cells. It caused a significant increase in apoptosis, accompanied by the stimulation of autophagy. Moreover, this formulation arrested T47D cells at the G2/M phase, promoted the reduction of the breast cancer stem cell (BCSC) population, and repressed the expression of TWIST-1 and ZEB-1. Conclusion: Co-delivery of NE-DTX+TQ may probably inhibit the proliferation of T47D via the induction of apoptosis and autophagy pathways and impede the migration by reducing the BCSC population and downregulating TWIST-1 expression to decrease the epithelial-to-mesenchymal transition (EMT) of breast cancer cells. Therefore, the study suggests the NE-DTX+TQ formula as a potential approach to inhibit breast cancer growth and metastasis.
{"title":"Growth and invasion inhibition of T47D ductal carcinoma cells by the association of docetaxel with a bioactive agent in neutral nanosuspension.","authors":"Raghdah S Bawadud, Mayson H Alkhatib","doi":"10.34172/bi.2023.23515","DOIUrl":"10.34172/bi.2023.23515","url":null,"abstract":"<p><p><i><b>Introduction:</b></i> The approach for drug delivery has impressively developed with the emergence of nanosuspension, particularly the targeted nanoemulsions (NEs). It can potentially improve the bioavailability of drugs, enhancing their therapeutic efficiency. This study aims to examine the potential role of NE as a delivery system for the combination of docetaxel (DTX), a microtubule-targeting agent, and thymoquinone (TQ) in the treatment of human ductal carcinoma cells T47D. <i><b>Methods:</b></i> NEs were synthesized by ultra-sonication and characterized physically by dynamic light scattering (DLS). A sulforhodamine B assay was performed to evaluate cytotoxicity, and a flow cytometry analysis for cell cycle, apoptosis, autophagy, and cancer stem cell evaluations. A quantitative polymerase chain reaction further assessed the epithelial-mesenchymal transition gene expirations of SNAIL-1, ZEB-1, and TWIST-1. <i><b>Results:</b></i> The optimal sizes of blank-NEs and NE-DTX+TQ were found at 117.3 ± 8 nm and 373 ± 6.8 nm, respectively. The synergistic effect of the NE-DTX+TQ formulation significantly inhibited the <i>in vitro</i> proliferation of T47D cells. It caused a significant increase in apoptosis, accompanied by the stimulation of autophagy. Moreover, this formulation arrested T47D cells at the G<sub>2</sub>/M phase, promoted the reduction of the breast cancer stem cell (BCSC) population, and repressed the expression of TWIST-1 and ZEB-1. <i><b>Conclusion:</b></i> Co-delivery of NE-DTX+TQ may probably inhibit the proliferation of T47D via the induction of apoptosis and autophagy pathways and impede the migration by reducing the BCSC population and downregulating TWIST-1 expression to decrease the epithelial-to-mesenchymal transition (EMT) of breast cancer cells. Therefore, the study suggests the NE-DTX+TQ formula as a potential approach to inhibit breast cancer growth and metastasis.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 2","pages":"145-157"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3f/a8/bi-13-145.PMC10182446.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9485470","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}
{"title":"The implications of pharmacogenomics in oncology.","authors":"Jean J Latimer","doi":"10.34172/bi.2023.27686","DOIUrl":"https://doi.org/10.34172/bi.2023.27686","url":null,"abstract":"","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"181-182"},"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/c0/22/bi-13-181.PMC10329749.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9816792","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}
Mina Yousefnezhad, Soodabeh Davaran, Mirzaagha Babazadeh, Abolfazl Akbarzadeh, Hamidreza Pazoki-Toroudi
Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment.
Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures.
Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells.
Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.
{"title":"PCL-based nanoparticles for doxorubicin-ezetimibe co-delivery: A combination therapy for prostate cancer using a drug repurposing strategy.","authors":"Mina Yousefnezhad, Soodabeh Davaran, Mirzaagha Babazadeh, Abolfazl Akbarzadeh, Hamidreza Pazoki-Toroudi","doi":"10.34172/bi.2023.24252","DOIUrl":"https://doi.org/10.34172/bi.2023.24252","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment.</p><p><strong>Methods: </strong>In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures.</p><p><strong>Results: </strong>The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells.</p><p><strong>Conclusion: </strong>Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"241-253"},"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/b1/18/bi-13-241.PMC10329752.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868847","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: Mesoporous silica nanoparticles (MSNPs) are considered innovative multifunctional structures for targeted drug delivery owing to their outstanding physicochemical characteristics.
Methods: MSNPs were fabricated using the sol-gel method, and polyethylene glycol-600 (PEG600) was used for MSNPs modification. Subsequently, sunitinib (SUN) was loaded into the MSNPs, MSNP-PEG and MSNP-PEG/SUN were grafted with mucin 16 (MUC16) aptamers. The nanosystems (NSs) were characterized using FT-IR, TEM, SEM, DLS, XRD, BJH, and BET. Furthermore, the biological impacts of MSNPs were evaluated on the ovarian cancer cells by MTT assay and flow cytometry analysis.
Results: The results revealed that the MSNPs have a spherical shape with an average dimension, pore size, and surface area of 56.10 nm, 2.488 nm, and 148.08 m2g-1, respectively. The cell viability results showed higher toxicity of targeted MSNPs in MUC16 overexpressing OVCAR-3 cells as compared to the SK-OV-3 cells; that was further confirmed by the cellular uptake results. The cell cycle analysis exhibited that the induction of sub-G1 phase arrest mostly occurred in MSNP-PEG/SUN-MUC16 treated OVCAR-3 cells and MSNP-PEG/SUN treated SK-OV-3 cells. DAPI staining showed apoptosis induction upon exposure to targeted MSNP in MUC16 positive OVCAR-3 cells.
Conclusion: According to our results, the engineered NSs could be considered an effective multifunctional targeted drug delivery platform for the mucin 16 overexpressing cells.
{"title":"Fabrication of mesoporous silica nanoparticles for targeted delivery of sunitinib to ovarian cancer cells.","authors":"Mitra Torabi, Ayuob Aghanejad, Pouria Savadi, Abolfazl Barzegari, Yadollah Omidi, Jaleh Barar","doi":"10.34172/bi.2023.25298","DOIUrl":"https://doi.org/10.34172/bi.2023.25298","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Mesoporous silica nanoparticles (MSNPs) are considered innovative multifunctional structures for targeted drug delivery owing to their outstanding physicochemical characteristics.</p><p><strong>Methods: </strong>MSNPs were fabricated using the sol-gel method, and polyethylene glycol-600 (PEG<sub>600</sub>) was used for MSNPs modification. Subsequently, sunitinib (SUN) was loaded into the MSNPs, MSNP-PEG and MSNP-PEG/SUN were grafted with mucin 16 (MUC16) aptamers. The nanosystems (NSs) were characterized using FT-IR, TEM, SEM, DLS, XRD, BJH, and BET. Furthermore, the biological impacts of MSNPs were evaluated on the ovarian cancer cells by MTT assay and flow cytometry analysis.</p><p><strong>Results: </strong>The results revealed that the MSNPs have a spherical shape with an average dimension, pore size, and surface area of 56.10 nm, 2.488 nm, and 148.08 m<sup>2</sup>g<sup>-1</sup>, respectively. The cell viability results showed higher toxicity of targeted MSNPs in MUC16 overexpressing OVCAR-3 cells as compared to the SK-OV-3 cells; that was further confirmed by the cellular uptake results. The cell cycle analysis exhibited that the induction of sub-G1 phase arrest mostly occurred in MSNP-PEG/SUN-MUC16 treated OVCAR-3 cells and MSNP-PEG/SUN treated SK-OV-3 cells. DAPI staining showed apoptosis induction upon exposure to targeted MSNP in MUC16 positive OVCAR-3 cells.</p><p><strong>Conclusion: </strong>According to our results, the engineered NSs could be considered an effective multifunctional targeted drug delivery platform for the mucin 16 overexpressing cells.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"13 3","pages":"255-267"},"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/90/5e/bi-13-255.PMC10329750.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868851","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":"13 3","pages":"229-240"},"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}