Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e23146
G. S. Raikar, A. S. Raikar, S. Somnache
The article explores the significance of biomarkers in clinical research and the advantages of utilizing artificial intelligence (AI) and machine learning (ML) in the discovery process. Biomarkers provide a more comprehensive understanding of disease progression and response to therapy compared to traditional indicators. AI and ML offer a new approach to biomarker discovery, leveraging large amounts of data to identify patterns and optimize existing biomarkers. Additionally, the article touches on the emergence of digital biomarkers, which use technology to assess an individual’s physiological and behavioural states, and the importance of properly processing omics and multi-omics data for efficient handling by computer systems. However, the article acknowledges the challenges posed by AI/ML in the identification of biomarkers, including potential biases in the data and the need for diversity in data representation. To address these challenges, the article suggests the importance of regulation and diversity in the development of AI/ML algorithms.
{"title":"Advancements in artificial intelligence and machine learning in revolutionising biomarker discovery","authors":"G. S. Raikar, A. S. Raikar, S. Somnache","doi":"10.1590/s2175-97902023e23146","DOIUrl":"https://doi.org/10.1590/s2175-97902023e23146","url":null,"abstract":"The article explores the significance of biomarkers in clinical research and the advantages of utilizing artificial intelligence (AI) and machine learning (ML) in the discovery process. Biomarkers provide a more comprehensive understanding of disease progression and response to therapy compared to traditional indicators. AI and ML offer a new approach to biomarker discovery, leveraging large amounts of data to identify patterns and optimize existing biomarkers. Additionally, the article touches on the emergence of digital biomarkers, which use technology to assess an individual’s physiological and behavioural states, and the importance of properly processing omics and multi-omics data for efficient handling by computer systems. However, the article acknowledges the challenges posed by AI/ML in the identification of biomarkers, including potential biases in the data and the need for diversity in data representation. To address these challenges, the article suggests the importance of regulation and diversity in the development of AI/ML algorithms.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67743392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e23068
Gabriela Suthovski, Alcione Santa Catarina, Diana Paula Perin, R. Mainardes, Karina Ramirez Starikoff, A. Gallina, Maiara Garcia Blagitz Azevedo, F. Dalmolin, Luciana Velasques Cervo, D. M. Benvegnú
Bovine infectious mastitis is largely resistant to antibacterial treatment, mainly due to mechanisms of bacterial resistance in the biofilms formed by Staphylococcus aureus. Melaleuca (MEO) and citronella essential oils (CEO) are promising agents for reducing or eliminating biofilms. Free melaleuca oil presented a medium Minimum Inhibitory Concentration (MIC) of 0.625% and a Minimum Bactericidal Concentration (MBC) of 1.250%, while free citronella oil showed medium MIC and MBC of 0.313%. Thus, free CEO and MEO demonstrate bacteriostatic and bactericidal potential. We generated polymeric nanocapsules containing MEO or CEO and evaluated their efficacy at reducing biofilms formed by S. aureus . Glass and polypropylene spheres were used as test surfaces. To compare the responses of free and encapsulated oils, strains were submitted to 10 different procedures, using free and nanoencapsulated essential oils (EOs) in vitro . We observed no biofilm reduction by MEO, free or nanoencapsulated. However, CEO nanocapsules reduced biofilm formation on glass (p = 0.03) and showed a tendency to diminish biofilms on polypropylene (p = 0.051). Despite nanoencapsulated CEO reducing biofilms in vitro , the formulation could be improved to modify the CEO component polarity and, including MEO, to obtain more interactions with surfaces and the biofilm matrix.
{"title":"Effect of polycaprolactone nanocapsules loaded with essential oils on biofilm formation by Staphylococcus aureus strains isolated from bovine mastitis cases","authors":"Gabriela Suthovski, Alcione Santa Catarina, Diana Paula Perin, R. Mainardes, Karina Ramirez Starikoff, A. Gallina, Maiara Garcia Blagitz Azevedo, F. Dalmolin, Luciana Velasques Cervo, D. M. Benvegnú","doi":"10.1590/s2175-97902023e23068","DOIUrl":"https://doi.org/10.1590/s2175-97902023e23068","url":null,"abstract":"Bovine infectious mastitis is largely resistant to antibacterial treatment, mainly due to mechanisms of bacterial resistance in the biofilms formed by Staphylococcus aureus. Melaleuca (MEO) and citronella essential oils (CEO) are promising agents for reducing or eliminating biofilms. Free melaleuca oil presented a medium Minimum Inhibitory Concentration (MIC) of 0.625% and a Minimum Bactericidal Concentration (MBC) of 1.250%, while free citronella oil showed medium MIC and MBC of 0.313%. Thus, free CEO and MEO demonstrate bacteriostatic and bactericidal potential. We generated polymeric nanocapsules containing MEO or CEO and evaluated their efficacy at reducing biofilms formed by S. aureus . Glass and polypropylene spheres were used as test surfaces. To compare the responses of free and encapsulated oils, strains were submitted to 10 different procedures, using free and nanoencapsulated essential oils (EOs) in vitro . We observed no biofilm reduction by MEO, free or nanoencapsulated. However, CEO nanocapsules reduced biofilm formation on glass (p = 0.03) and showed a tendency to diminish biofilms on polypropylene (p = 0.051). Despite nanoencapsulated CEO reducing biofilms in vitro , the formulation could be improved to modify the CEO component polarity and, including MEO, to obtain more interactions with surfaces and the biofilm matrix.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67743188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e22476
Ji Wu, Yong Li, Xinju Li, Tao Wu
The aim of the present study was to investigate the effect of swertiamarin (STM) in attenuating paraquat (PQ)-induced human lung alveolar epithelial-like cell (A549) apoptosis and the underlying mechanisms. A549 cells were pretreated with different concentrations of STM for 2 hr and then cultured with or without PQ (700 μM) for 24 hr. Cell survival was determined using the CCK8 assay. Morphological changes, MDA content, inflammatory factors, fibrogenesis parameters, apoptosis rates, redox status and mitochondrial membrane potential (MMP) were evaluated. The expression of several genes involved in the modulation of redox status was measured by Western blotting. Cell viability and MMP were decreased, but the apoptosis rate and DCFH oxidation were elevated by PQ exposure. STM pretreatment notably increased cell viability and MMP and reduced the apoptosis rate and DCFH oxidation. Furthermore, TLR4-NOX4 signaling was significantly inhibited by STM. The downregulation of NOX4 by siRNA exerted the same protective effects as STM. This study provides the first evidence that STM attenuates PQ-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function.
{"title":"Swertiamarin attenuates paraquat-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function","authors":"Ji Wu, Yong Li, Xinju Li, Tao Wu","doi":"10.1590/s2175-97902023e22476","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22476","url":null,"abstract":"The aim of the present study was to investigate the effect of swertiamarin (STM) in attenuating paraquat (PQ)-induced human lung alveolar epithelial-like cell (A549) apoptosis and the underlying mechanisms. A549 cells were pretreated with different concentrations of STM for 2 hr and then cultured with or without PQ (700 μM) for 24 hr. Cell survival was determined using the CCK8 assay. Morphological changes, MDA content, inflammatory factors, fibrogenesis parameters, apoptosis rates, redox status and mitochondrial membrane potential (MMP) were evaluated. The expression of several genes involved in the modulation of redox status was measured by Western blotting. Cell viability and MMP were decreased, but the apoptosis rate and DCFH oxidation were elevated by PQ exposure. STM pretreatment notably increased cell viability and MMP and reduced the apoptosis rate and DCFH oxidation. Furthermore, TLR4-NOX4 signaling was significantly inhibited by STM. The downregulation of NOX4 by siRNA exerted the same protective effects as STM. This study provides the first evidence that STM attenuates PQ-induced pulmonary epithelial-like cell apoptosis via NOX4-mediated regulation of redox and mitochondrial function.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67741942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e22394
Qijia Xu, Kai Wang, Yaoyao Xu, Yinhe Gao, Ge Wang, Sheng Liu, Feng Zhao
This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma.
{"title":"Research on Anti-inflammatory Targets and Mechanisms of alkaloids in Picrasma quassioides Benn Through Network Pharmacology","authors":"Qijia Xu, Kai Wang, Yaoyao Xu, Yinhe Gao, Ge Wang, Sheng Liu, Feng Zhao","doi":"10.1590/s2175-97902023e22394","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22394","url":null,"abstract":"This study aimed to investigate the molecular mechanism of Picrasma quassioides Benn against inflammation by means of network pharmacology. The paper will provide a reference for multi-target and multi-channel treatment of inflammation with traditional Chinese medicine. Through screening and analysis, 11 active ingredients and 109 anti-inflammation prediction targets were obtained and constructed a compound-target network. The targets such as VEGFA, TLR4 and STAT3 may play a crucial role. Network enrichment analysis showed that the 109 potential targets constitute a number of pathways or inflammatory reactions closely related to inflammation, including NF-κB signaling pathway and MAPK signaling pathway. The docking results indicated that the binding energy of Picrasidine Y and the inflammatory factors VEGFA is the highest. This study predicted the role of multiple active compounds in the alkaloids of Picrasma in the inflammatory response, and provided a theoretical basis for the anti-inflammatory mechanism of Picrasma.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e22802
J. R. Gonçalves, Giordano Avancini Sole, A. Cavaco
This study aimed to characterize and compare medicines formularies (MFs) used in Long-Term Care (LTC) facilities in Portugal, and to identify the prevalence of Potentially Inappropriate Medicines (PIMs). A systematic contact with LTC facilities was undertaken in December 2021. MFs were systematized according to the Anatomical Therapeutical Chemical classification system (ATC), followed by descriptive content analysis. A structured comparison between MFs developed by public organizations and private LTC facilities was performed. After duplicate removal and exclusion of medicines not for systemic use, two explicit criteria - the Algorithm of medication review in frail older people and the EU(7)-PIM list - were employed for PIMs identification. Five MFs were obtained and assessed. The three MFs developed by private institutions covered 23% of the national LTC facilities and approximately 34% of the national total of beds. Heterogeneity was particularly high for the Alimentary tract and metabolism , Blood and blood-forming organs , Musculoskeletal system , and Respiratory system ATC groups. A PIM prevalence of 29,4% was identified. Medicines distribution between the MFs suggests the need to develop national guidelines towards harmonizing medicines usage in LTC. The prevalence of PIMs found highlights the importance of a particular optimized use of this health technology in aged sub-populations.
{"title":"Long-Term Care medicines formularies: any reasons for pharmacists’ concern?","authors":"J. R. Gonçalves, Giordano Avancini Sole, A. Cavaco","doi":"10.1590/s2175-97902023e22802","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22802","url":null,"abstract":"This study aimed to characterize and compare medicines formularies (MFs) used in Long-Term Care (LTC) facilities in Portugal, and to identify the prevalence of Potentially Inappropriate Medicines (PIMs). A systematic contact with LTC facilities was undertaken in December 2021. MFs were systematized according to the Anatomical Therapeutical Chemical classification system (ATC), followed by descriptive content analysis. A structured comparison between MFs developed by public organizations and private LTC facilities was performed. After duplicate removal and exclusion of medicines not for systemic use, two explicit criteria - the Algorithm of medication review in frail older people and the EU(7)-PIM list - were employed for PIMs identification. Five MFs were obtained and assessed. The three MFs developed by private institutions covered 23% of the national LTC facilities and approximately 34% of the national total of beds. Heterogeneity was particularly high for the Alimentary tract and metabolism , Blood and blood-forming organs , Musculoskeletal system , and Respiratory system ATC groups. A PIM prevalence of 29,4% was identified. Medicines distribution between the MFs suggests the need to develop national guidelines towards harmonizing medicines usage in LTC. The prevalence of PIMs found highlights the importance of a particular optimized use of this health technology in aged sub-populations.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67743300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
. Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague–Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings.
{"title":"Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid","authors":"Dazhi Wang, Meihua Jiang, Xiaowen Wang, Chen Wang, Xiaoyu Ou, Lei Shang","doi":"10.1590/s2175-97902023e22690","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22690","url":null,"abstract":". Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague–Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e23017
N. Kahramansoy, M. Çelebier
Infusion solutions must be stable from the production stage until the infusion stage. Some infusion fluids contain degradation products, known as advanced glycation end products (AGEs); however, it is unknown whether AGEs exist in parenteral nutrition solutions. We aimed to investigate this question and test the effect of infusion conditions on AGE formation in parenteral nutrition solution. Nine parenteral nutrition solutions were supplied by the pharmacy with which we collaborated. To simulate the infusion conditions, the solutions were held in a patient room with standard lighting and temperature for 24 hours. Samples were taken at the beginning (group A) and the end (24th hour, group B) of the infusion period. The degradation products were 3-deoxyglucosone, pentosidine, N-carboxymethyl lysine, and 4-hydroxynonenal, which we investigated by high-performance liquid chromatography-mass spectrometry (LC-MS) and Q-TOF LC/MS methods. Two of four degradation products, 4-hydroxynonenal and N-carboxymethyl lysine, were detected in all samples, and Group B had higher levels of both compounds compared to Group A, who showed that the quantities of these compounds increased in room conditions over time. The increase was significant for 4-hydroxynonenal (p=0.03), but not for N-carboxymethyl lysine (p=0.23). Moreover, we detected in the parenteral nutrition solutions a compound that could have been 4-hydroxy-2-butynal or furanone.
{"title":"Existence of advanced glycation / lipoxidation end-products in parenteral nutrition solutions and effects of infusion conditions on their levels","authors":"N. Kahramansoy, M. Çelebier","doi":"10.1590/s2175-97902023e23017","DOIUrl":"https://doi.org/10.1590/s2175-97902023e23017","url":null,"abstract":"Infusion solutions must be stable from the production stage until the infusion stage. Some infusion fluids contain degradation products, known as advanced glycation end products (AGEs); however, it is unknown whether AGEs exist in parenteral nutrition solutions. We aimed to investigate this question and test the effect of infusion conditions on AGE formation in parenteral nutrition solution. Nine parenteral nutrition solutions were supplied by the pharmacy with which we collaborated. To simulate the infusion conditions, the solutions were held in a patient room with standard lighting and temperature for 24 hours. Samples were taken at the beginning (group A) and the end (24th hour, group B) of the infusion period. The degradation products were 3-deoxyglucosone, pentosidine, N-carboxymethyl lysine, and 4-hydroxynonenal, which we investigated by high-performance liquid chromatography-mass spectrometry (LC-MS) and Q-TOF LC/MS methods. Two of four degradation products, 4-hydroxynonenal and N-carboxymethyl lysine, were detected in all samples, and Group B had higher levels of both compounds compared to Group A, who showed that the quantities of these compounds increased in room conditions over time. The increase was significant for 4-hydroxynonenal (p=0.03), but not for N-carboxymethyl lysine (p=0.23). Moreover, we detected in the parenteral nutrition solutions a compound that could have been 4-hydroxy-2-butynal or furanone.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e18705
P. Gong
Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.
{"title":"Egr-1 Enhances Drug Resistance of Breast Cancer Cells by MDR1 Dependence","authors":"P. Gong","doi":"10.1590/s2175-97902023e18705","DOIUrl":"https://doi.org/10.1590/s2175-97902023e18705","url":null,"abstract":"Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67736794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e23011
I. Vieira, Ana Clara Lima Nunes Silva, N. Castro, Cristal S C Pinto, Z. Freitas, E. Ricci-Júnior, E. P. Santos, A. L. Camara, M. C. P. Costa, Carlos Adam Conte-Junior
Oil-in-water photoprotective nanoemulsions (NEs) were developed using Babassu (BBS) lipophilic extract, nonionic surfactants, and low concentrations of organic sunscreens by ultrasonic processing. BBS extract was chosen due to its suitable physicochemical properties (acidity index, peroxide index, refraction index, and relative density) and predominance of saturated fatty acids, identified by gas chromatography-mass spectrometry (GC-MS), which promote biological activities and high oxidative stability. NEs were characterized by mean droplet size, morphology, polydispersity index (PdI), pH, and organoleptic properties, and the physical stability of the NEs was evaluated for 120 days at room temperature. The sun protection factor (SPF) was determined, and the photostability and in vitro cytotoxicity assays were performed for NEs. All NEs remained stable for 120 days, with a droplet size <150 nm and a monomodal distribution profile. The pH values were compatible with the skin’s pH. NE3 showed a spherical morphology, with a mean droplet size of 125.15 ± 0.16 nm and PdI of 0.145 ± 0.032. NE3 containing BBS extract and sunscreens presented an SPF of 35.5 ± 3.0, was photostable after 6 h of radiation and was non-cytotoxic to fibroblast cells. Thus, NE3 could be considered a promising formulation for developing synergic plant-extract sunscreen photoprotective products for the market.
{"title":"Development and characterization of photoprotective nanoemulsions containing Babassu (Orbignya phalerata Mart.) lipophilic extract","authors":"I. Vieira, Ana Clara Lima Nunes Silva, N. Castro, Cristal S C Pinto, Z. Freitas, E. Ricci-Júnior, E. P. Santos, A. L. Camara, M. C. P. Costa, Carlos Adam Conte-Junior","doi":"10.1590/s2175-97902023e23011","DOIUrl":"https://doi.org/10.1590/s2175-97902023e23011","url":null,"abstract":"Oil-in-water photoprotective nanoemulsions (NEs) were developed using Babassu (BBS) lipophilic extract, nonionic surfactants, and low concentrations of organic sunscreens by ultrasonic processing. BBS extract was chosen due to its suitable physicochemical properties (acidity index, peroxide index, refraction index, and relative density) and predominance of saturated fatty acids, identified by gas chromatography-mass spectrometry (GC-MS), which promote biological activities and high oxidative stability. NEs were characterized by mean droplet size, morphology, polydispersity index (PdI), pH, and organoleptic properties, and the physical stability of the NEs was evaluated for 120 days at room temperature. The sun protection factor (SPF) was determined, and the photostability and in vitro cytotoxicity assays were performed for NEs. All NEs remained stable for 120 days, with a droplet size <150 nm and a monomodal distribution profile. The pH values were compatible with the skin’s pH. NE3 showed a spherical morphology, with a mean droplet size of 125.15 ± 0.16 nm and PdI of 0.145 ± 0.032. NE3 containing BBS extract and sunscreens presented an SPF of 35.5 ± 3.0, was photostable after 6 h of radiation and was non-cytotoxic to fibroblast cells. Thus, NE3 could be considered a promising formulation for developing synergic plant-extract sunscreen photoprotective products for the market.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67743420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-28DOI: 10.1590/s2175-97902023e23063
M. Barreto, J. L. Carvalho, M. Melo, A. Michel, M. G. Ferreira, Ruthnéa Aparecida Lázaro Muzzi, A. Goes, M. M. Melo
Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox + CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells.
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