A. Gawędzka, J. Drąg, M. Knapik-Czajka, Małgorzata Belczyk, Angelika Szafran, Iga Szlachta
Statins are one of the most commonly used lipid-lowering drugs reducing the risk of mortality due to cardiovascular diseases. They are well tolerated and have relatively few side effects which mainly affect skeletal muscle. The impact of statins on skeletal muscle functions depends on the composition of the muscle fibers type. One of the mechanisms of statin-induced myopathy is imbalance between muscle protein synthesis and breakdown.Transcription factor FoxO3a is a key factor regulating muscle protein breakdown. The activity of FoxO3a is regulated namely by phosphorylation via PI3K/Akt pathway. Active, phosphorylated Akt catalyzes the phosphorylation and thus inactivation of FoxO3a. The purpose of our study was to evaluate the effect of atorvastatin on FoxO3a and Akt in different skeletal muscles in rats with diet-induced hypercholesterolemia. Atorvastatin (20 mg/kg b.w./day) or the vehicle was administered orally 21 days. FoxO3a, Akt and their phosphorylated protein levels were assayed by Western blot in gastrocnemius and soleus muscle. Additionally, muscle total protein level and serum CK activity were measured. In the gastrocnemius muscle atorvastatin decreased total FoxO3a and P-FoxO3a levels with no changes in Akt and P-Akt level. In contrast, in soleus muscle atorvastatin did not change the level of P-FoxO3a. However, total FoxO3a and the P-Akt level decreased. Serum CK activity did not change in both muscle under atorvastatin treatment. In conclusion, the results of our study indicate that atorvastatin affects FoxO3a and Akt in a muscle type-dependent manner.
{"title":"Skeletal Muscle Type-Dependent Effect of Atorvastatin on FoxO3a and Akt in Hypercholesterolemic Rats","authors":"A. Gawędzka, J. Drąg, M. Knapik-Czajka, Małgorzata Belczyk, Angelika Szafran, Iga Szlachta","doi":"10.32383/appdr/174241","DOIUrl":"https://doi.org/10.32383/appdr/174241","url":null,"abstract":"Statins are one of the most commonly used lipid-lowering drugs reducing the risk of mortality due to cardiovascular diseases. They are well tolerated and have relatively few side effects which mainly affect skeletal muscle. The impact of statins on skeletal muscle functions depends on the composition of the muscle fibers type. One of the mechanisms of statin-induced myopathy is imbalance between muscle protein synthesis and breakdown.Transcription factor FoxO3a is a key factor regulating muscle protein breakdown. The activity of FoxO3a is regulated namely by phosphorylation via PI3K/Akt pathway. Active, phosphorylated Akt catalyzes the phosphorylation and thus inactivation of FoxO3a. The purpose of our study was to evaluate the effect of atorvastatin on FoxO3a and Akt in different skeletal muscles in rats with diet-induced hypercholesterolemia. Atorvastatin (20 mg/kg b.w./day) or the vehicle was administered orally 21 days. FoxO3a, Akt and their phosphorylated protein levels were assayed by Western blot in gastrocnemius and soleus muscle. Additionally, muscle total protein level and serum CK activity were measured. In the gastrocnemius muscle atorvastatin decreased total FoxO3a and P-FoxO3a levels with no changes in Akt and P-Akt level. In contrast, in soleus muscle atorvastatin did not change the level of P-FoxO3a. However, total FoxO3a and the P-Akt level decreased. Serum CK activity did not change in both muscle under atorvastatin treatment. In conclusion, the results of our study indicate that atorvastatin affects FoxO3a and Akt in a muscle type-dependent manner.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139231721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z. Mitkova, M. Doneva, M. Dimitrova, Petya Nikolova, K. Tachkov, G. Petrova
Evaluation of rational drug utilization (RDU) through WHO indicators is used to provide information about the level of development of national policy and to identify the necessity of further regulatory, patients or healthcare professionals -centered measures. The current study aims to investigatethe patients’ perspective about medicines utilization by implementing the WHO’s "followup" indicators in the Bulgarian practice. A prospective, cross -sectional, online inquiry study was conducted among Bulgarian population. The population above 18 years of age is 5.8 million of people and 400 people sample was considered sufficient with 95% CI. The study methodology is based on a modified version of the WHO "followup" indicators. The total number of answers was 467. The majority of patients aged over 56 years responded that they did not receive enough information about the side effects and interactions of the prescribed medicines and the most often they used the leaflet as a source of information. Most of the patients responded they always check the expiry date (61%), while 23 % of patients check it sometimes. In the group of patients over 65 years, 24% responded that they never check the expiry date. The results of our study suggest that rational medicines utilization is a broader concept depending on patients' knowledge and pharmacists and patients relation. It suggests that there is a need to educate both parties, mainly to increase health literacy and promote general aspects of rational medicines utilization.
{"title":"Analysis Of Patients' Opinion Of Prescribed Medicines: A Questionnaire - Based Pilot Study In Bulgaria","authors":"Z. Mitkova, M. Doneva, M. Dimitrova, Petya Nikolova, K. Tachkov, G. Petrova","doi":"10.32383/appdr/173228","DOIUrl":"https://doi.org/10.32383/appdr/173228","url":null,"abstract":"Evaluation of rational drug utilization (RDU) through WHO indicators is used to provide information about the level of development of national policy and to identify the necessity of further regulatory, patients or healthcare professionals -centered measures. The current study aims to investigatethe patients’ perspective about medicines utilization by implementing the WHO’s \"followup\" indicators in the Bulgarian practice. A prospective, cross -sectional, online inquiry study was conducted among Bulgarian population. The population above 18 years of age is 5.8 million of people and 400 people sample was considered sufficient with 95% CI. The study methodology is based on a modified version of the WHO \"followup\" indicators. The total number of answers was 467. The majority of patients aged over 56 years responded that they did not receive enough information about the side effects and interactions of the prescribed medicines and the most often they used the leaflet as a source of information. Most of the patients responded they always check the expiry date (61%), while 23 % of patients check it sometimes. In the group of patients over 65 years, 24% responded that they never check the expiry date. The results of our study suggest that rational medicines utilization is a broader concept depending on patients' knowledge and pharmacists and patients relation. It suggests that there is a need to educate both parties, mainly to increase health literacy and promote general aspects of rational medicines utilization.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139228648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bahar Isik, I. Ates, B. Suleyman, R. Mammadov, S. Bulut, M. Gulaboglu, Adalet Ozcicek, H. Suleyman
The increase in cyclooxygenase-2 (COX-2) activity and the decrease in COX-1 activity were associated with increased intracellular calcium. Lacidipine, a calcium channel blocker, can protect gastric tissue from aspirin-induced damage while potentiating the analgesic and anti-inflammatory properties of aspirin. This study, it was aimed to investigate the anti-inflammatory, analgesic, and gastric tissue effects of using lacidipine and aspirin combination, and separately. (LA). Twenty-four rats were randomly divided into CG (carrageenan control), LCG (carrageenan+lacidipine), ACG (carrageenan+aspirin), and LACG (carrageenan+LA) groups. Lacidipine 4 mg/kg, aspirin 100 mg/kg were given orally to the animals on an empty stomach. ,Carrageenan was injected into the foot paws of rats to induce inflammation and pain. Paw volumes were measured at 0, 1, and 4 hours after carrageenan administration, and paw pain thresholds were measured at 1 and 4 hours. After euthanasia (thiopental sodium, 50 mg/kg), paw and gastric tissues were excised and biochemically analyzed. Gastric tissues were also examined macroscopically. In the paw tissues of animals receiving lacidipine, malondialdehyde (MDA) was lower than in the CG and AG, while total glutathione (tGSH) was higher (p<0.05). Lacidipine inhibited COX-2, but not COX-1 isoenzyme. LA, lacidipine, and aspirin inhibited inflammation and hyperalgesia at 1 and 4 hours, respectively. Lacidipine prevented aspirin-induced COX-1 inhibition and gastric ulcer formation. Lacidipine combined with aspirin may be beneficial in initiating its anti-inflammatory activity early, achieving a potent analgesic effect, and preventing aspirin-induced gastric injury.
{"title":"Anti-inflammatory, Analgesic, and Gastric Tissue Effects of Lacidipine, Aspirin, and Their Combination","authors":"Bahar Isik, I. Ates, B. Suleyman, R. Mammadov, S. Bulut, M. Gulaboglu, Adalet Ozcicek, H. Suleyman","doi":"10.32383/appdr/172400","DOIUrl":"https://doi.org/10.32383/appdr/172400","url":null,"abstract":"The increase in cyclooxygenase-2 (COX-2) activity and the decrease in COX-1 activity were associated with increased intracellular calcium. Lacidipine, a calcium channel blocker, can protect gastric tissue from aspirin-induced damage while potentiating the analgesic and anti-inflammatory properties of aspirin. This study, it was aimed to investigate the anti-inflammatory, analgesic, and gastric tissue effects of using lacidipine and aspirin combination, and separately. (LA). Twenty-four rats were randomly divided into CG (carrageenan control), LCG (carrageenan+lacidipine), ACG (carrageenan+aspirin), and LACG (carrageenan+LA) groups. Lacidipine 4 mg/kg, aspirin 100 mg/kg were given orally to the animals on an empty stomach. ,Carrageenan was injected into the foot paws of rats to induce inflammation and pain. Paw volumes were measured at 0, 1, and 4 hours after carrageenan administration, and paw pain thresholds were measured at 1 and 4 hours. After euthanasia (thiopental sodium, 50 mg/kg), paw and gastric tissues were excised and biochemically analyzed. Gastric tissues were also examined macroscopically. In the paw tissues of animals receiving lacidipine, malondialdehyde (MDA) was lower than in the CG and AG, while total glutathione (tGSH) was higher (p<0.05). Lacidipine inhibited COX-2, but not COX-1 isoenzyme. LA, lacidipine, and aspirin inhibited inflammation and hyperalgesia at 1 and 4 hours, respectively. Lacidipine prevented aspirin-induced COX-1 inhibition and gastric ulcer formation. Lacidipine combined with aspirin may be beneficial in initiating its anti-inflammatory activity early, achieving a potent analgesic effect, and preventing aspirin-induced gastric injury.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139232609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou
The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.
{"title":"Novel CDK4/6 lnhibitor, WXJ-8 -Exerts Anti-effects Through Cell Cycle in Breast Cancer","authors":"Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou","doi":"10.32383/appdr/173986","DOIUrl":"https://doi.org/10.32383/appdr/173986","url":null,"abstract":"The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139249774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Gawron, D. Piotrowska, G. Andrei, D. Schols, R. Snoeck, I. Głowacka
A new series of N-(diethylphosphonoalkyl)-1,8-naphthalimides were synthesized via direct reaction of 1,8-naphthalic anhydride or its 3-nitro- and 4-bromo- derivatives with selected ɷ-aminoalkylphosphonates and evaluated against a broad-spectrum of viruses as well as for their cytostatic properties toward selected cell lines. N-(diethylphosphonomethyl)-3-nitro-1,8-naphthalimide 15a exhibited inhibitory activity toward coxsackie virus B4 in Vero cells (EC50 = 9.45 μM), whereas 3-nitro-1,8-naphthalimides 15b and 15d containing short 2-carbon linker showed moderate activity against herpes simplex virus-2 (G) and herpes simplex virus-1 TK– KOS ACVr. Furthermore, compounds 15a, 15b and 15d showed antiviral potency against human coronavirus. Several naphthalimides exhibited cytostatic activity toward tested cancerous cell lines as well as normal retina cells. Transformation of selected diethyl phosphonates 13, 14 and 15 into ammonium phosphonates 21, 22 and 23 improved the solubility, however, did not result in the enhancement of antiviral and cytostatic potency of the compounds.
{"title":"Synthesis, Antiviral and Cytostatic Activity of New Series of Naphthalimide Derivatives","authors":"Katarzyna Gawron, D. Piotrowska, G. Andrei, D. Schols, R. Snoeck, I. Głowacka","doi":"10.32383/appdr/171434","DOIUrl":"https://doi.org/10.32383/appdr/171434","url":null,"abstract":"A new series of N-(diethylphosphonoalkyl)-1,8-naphthalimides were synthesized via direct reaction of 1,8-naphthalic anhydride or its 3-nitro- and 4-bromo- derivatives with selected ɷ-aminoalkylphosphonates and evaluated against a broad-spectrum of viruses as well as for their cytostatic properties toward selected cell lines. N-(diethylphosphonomethyl)-3-nitro-1,8-naphthalimide 15a exhibited inhibitory activity toward coxsackie virus B4 in Vero cells (EC50 = 9.45 μM), whereas 3-nitro-1,8-naphthalimides 15b and 15d containing short 2-carbon linker showed moderate activity against herpes simplex virus-2 (G) and herpes simplex virus-1 TK– KOS ACVr. Furthermore, compounds 15a, 15b and 15d showed antiviral potency against human coronavirus. Several naphthalimides exhibited cytostatic activity toward tested cancerous cell lines as well as normal retina cells. Transformation of selected diethyl phosphonates 13, 14 and 15 into ammonium phosphonates 21, 22 and 23 improved the solubility, however, did not result in the enhancement of antiviral and cytostatic potency of the compounds.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"32 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Kus, Maria Sygit, Maciuszek-Bartkowska Barbara, P. Ratajczak, A. Paczkowska, Dorota Kopciuch, T. Zaprutko
Medical databases are crucial tools in medicine and pharmacy, aiding studies on the impact of medical products on health and informing treatment decisions. However, prescribers must blend database insights with clinical expertise for accurate choices. Clinical experience doesn't always align with drug Summaries of Product Characteristics (SPCs). While SPC guidelines ensure safety, they might not optimize efficacy. For instance, treating Polycystic Ovary Syndrome (PCOS) often benefits from off-label therapies that are clinically and cost-effective. The study aimed to identify potential PCOS treatments beyond approved uses in Poland and globally. The methodology involved reviewing databases used by medical professionals. Out of 29, 11 databases were chosen based on off-label drug availability and relevance to PCOS. Results show that medical databases aid medical professionals in finding off-label PCOS treatments. These databases also assess a drug's potential efficacy and risks. However, their usefulness has limits, lacking comprehensive data on usage, mechanisms, and safety. When using literary databases, keyword selection significantly influences search results.
{"title":"Polycystic Ovary Syndrome (PCOS) - The Application of Selected off-label drugs found in medical databases","authors":"K. Kus, Maria Sygit, Maciuszek-Bartkowska Barbara, P. Ratajczak, A. Paczkowska, Dorota Kopciuch, T. Zaprutko","doi":"10.32383/appdr/172065","DOIUrl":"https://doi.org/10.32383/appdr/172065","url":null,"abstract":"Medical databases are crucial tools in medicine and pharmacy, aiding studies on the impact of medical products on health and informing treatment decisions. However, prescribers must blend database insights with clinical expertise for accurate choices. Clinical experience doesn't always align with drug Summaries of Product Characteristics (SPCs). While SPC guidelines ensure safety, they might not optimize efficacy. For instance, treating Polycystic Ovary Syndrome (PCOS) often benefits from off-label therapies that are clinically and cost-effective. The study aimed to identify potential PCOS treatments beyond approved uses in Poland and globally. The methodology involved reviewing databases used by medical professionals. Out of 29, 11 databases were chosen based on off-label drug availability and relevance to PCOS. Results show that medical databases aid medical professionals in finding off-label PCOS treatments. These databases also assess a drug's potential efficacy and risks. However, their usefulness has limits, lacking comprehensive data on usage, mechanisms, and safety. When using literary databases, keyword selection significantly influences search results.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"23 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to prepare a novel multifunctional magnetic nanoparticle (MNP) with a drug-loadable encapsulation and a matrix metalloproteinase (MMP) substrate-modified TAT peptide whose transmembrane ability can be activated in an MMP-rich environment, and to evaluate the uptake of this nanoparticle by cells, as well as its cytotoxicity. Nanoparticles were synthesized and modified with TAT or MMPs-TAT peptides. PC-3 cells and RWPE-1 cells were cultured with these nanoparticles at different concentrations, with or without MMP-2 pretreatment, and their uptake rate and toxicity were determined using flow cytometry and fluorescence microscopy. The nanoparticles were characterized with TEM (transmission electron microscopy) and DLS (dynamic light scattering). The diameter of these nanoparticles ranged from 194.5 ± 69.4 nm to 353.1 ± 103.9 nm, which were in the ideal range for application. The cellular uptake of MMPs-TAT-MNPs appeared similar to MNPs, but significantly increased in the presence of MMP-2 pretreatment. MMPs-TAT-MNPs had no significant cytotoxicity at the concentration of ≤25 μg/ml. MMPs-TAT-MNPs with MMP-2 substrate modified TAT peptide is successfully prepared, possess a low cytotoxicity loadable cargo and can be activated in an MMP-2 rich niche.
{"title":"Synthesis and Verification of a Novel Attainable Tumor Targeting Magnetic Nanoparticle","authors":"Yingxiu Chen, Jiasheng Yan","doi":"10.32383/appdr/173984","DOIUrl":"https://doi.org/10.32383/appdr/173984","url":null,"abstract":"This study aimed to prepare a novel multifunctional magnetic nanoparticle (MNP) with a drug-loadable encapsulation and a matrix metalloproteinase (MMP) substrate-modified TAT peptide whose transmembrane ability can be activated in an MMP-rich environment, and to evaluate the uptake of this nanoparticle by cells, as well as its cytotoxicity. Nanoparticles were synthesized and modified with TAT or MMPs-TAT peptides. PC-3 cells and RWPE-1 cells were cultured with these nanoparticles at different concentrations, with or without MMP-2 pretreatment, and their uptake rate and toxicity were determined using flow cytometry and fluorescence microscopy. The nanoparticles were characterized with TEM (transmission electron microscopy) and DLS (dynamic light scattering). The diameter of these nanoparticles ranged from 194.5 ± 69.4 nm to 353.1 ± 103.9 nm, which were in the ideal range for application. The cellular uptake of MMPs-TAT-MNPs appeared similar to MNPs, but significantly increased in the presence of MMP-2 pretreatment. MMPs-TAT-MNPs had no significant cytotoxicity at the concentration of ≤25 μg/ml. MMPs-TAT-MNPs with MMP-2 substrate modified TAT peptide is successfully prepared, possess a low cytotoxicity loadable cargo and can be activated in an MMP-2 rich niche.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"31 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka
This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.
{"title":"Stability of API as a Key Parameter for New Formulations Development - A Case Study of Rosuvastatin Calcium","authors":"Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka","doi":"10.32383/appdr/174028","DOIUrl":"https://doi.org/10.32383/appdr/174028","url":null,"abstract":"This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"23 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139251078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Hur, Sanghee Kim, Bo-ra Yoon, Guijae Yoo, In-Hae Choi, Ho-Young Park, Sang Yoon Choi
Obesity is caused by excessive adipogenesis and leads to metabolic diseases such as diabetes, hypertension, and degenerative arthritis. Therefore, there is an ever-increasing need to identify new anti-obesity compounds. In this study, the anti-obesity effects of (E)-3-(4-(tert-butyl)phenyl)-N-isobutyl-2-methylacrylamide (BPIMA) were evaluated using pre-adipocytes and a high-fat-fed C57BL/6J mouse model. As the results, BPIMA effectively inhibited adipocyte differentiation (64.3% at 40 μM) without exhibiting any cytotoxicity. Additionally, BPIMA decreased the protein levels of PPARγ, FAS, C/EBP, and SREBP in 3T3-L1 cells in a concentration-dependent manner. In C57BL/6J mice, a significant decrease in body weight, adipose tissue, and fatty liver was observed in the BPIMA-treated high-fat group compared to that observed in the vehicle-treated high-fat group; the serum levels of total cholesterol and glucose also significantly decreased in the BPIMA-treated high-fat group. Moreover, the weight and fat level of liver and serum AST, ALT activity in the BPIMA-treated high-fat group were similar to low fat diet-control group. These findings show that BPIMA may be a potential anti-obesity compound.
{"title":"(E)-3-(4-(tert-Butyl)Phenyl)-N-Isobutyl-2-Methylacrylamide Suppresses Adipogenesis in High-Fat-Fed Mice","authors":"J. Hur, Sanghee Kim, Bo-ra Yoon, Guijae Yoo, In-Hae Choi, Ho-Young Park, Sang Yoon Choi","doi":"10.32383/appdr/171509","DOIUrl":"https://doi.org/10.32383/appdr/171509","url":null,"abstract":"Obesity is caused by excessive adipogenesis and leads to metabolic diseases such as diabetes, hypertension, and degenerative arthritis. Therefore, there is an ever-increasing need to identify new anti-obesity compounds. In this study, the anti-obesity effects of (E)-3-(4-(tert-butyl)phenyl)-N-isobutyl-2-methylacrylamide (BPIMA) were evaluated using pre-adipocytes and a high-fat-fed C57BL/6J mouse model. As the results, BPIMA effectively inhibited adipocyte differentiation (64.3% at 40 μM) without exhibiting any cytotoxicity. Additionally, BPIMA decreased the protein levels of PPARγ, FAS, C/EBP, and SREBP in 3T3-L1 cells in a concentration-dependent manner. In C57BL/6J mice, a significant decrease in body weight, adipose tissue, and fatty liver was observed in the BPIMA-treated high-fat group compared to that observed in the vehicle-treated high-fat group; the serum levels of total cholesterol and glucose also significantly decreased in the BPIMA-treated high-fat group. Moreover, the weight and fat level of liver and serum AST, ALT activity in the BPIMA-treated high-fat group were similar to low fat diet-control group. These findings show that BPIMA may be a potential anti-obesity compound.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"108 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tong Chen, Pan-Pan Wei, Mengyue Deng, Yuzhen Ding, Die Xia, Zijun Yan
Oxidative stress is associated with the development of many diseases, such as chronic inflammation, cardiovascular disease and cancer. Antioxidants can scavenge free radicals in the body, reduce the production of reactive oxygen species (ROS) and effectively prevent oxidative stress. Polysaccharide is a antioxidants that widely found in natural resources, which is a kind of high molecular polymer with antioxidant activity. It can prevent oxidative stress and play a role in disease prevention through various mechanisms. In this paper, the different types of polysaccharides were summarized, such as plant polysaccharides, algal polysaccharides, microbial polysaccharides and animal polysaccharides, and their antioxidant mechanism and application in the treatment of disease were also discussed. we hope this review can offer some theoretical basis and inspiration for the antioxidant activity study and application of polysaccharides from natural resources.
{"title":"Antioxidant Activity of Polysaccharides From Natural Sources","authors":"Tong Chen, Pan-Pan Wei, Mengyue Deng, Yuzhen Ding, Die Xia, Zijun Yan","doi":"10.32383/appdr/173189","DOIUrl":"https://doi.org/10.32383/appdr/173189","url":null,"abstract":"Oxidative stress is associated with the development of many diseases, such as chronic inflammation, cardiovascular disease and cancer. Antioxidants can scavenge free radicals in the body, reduce the production of reactive oxygen species (ROS) and effectively prevent oxidative stress. Polysaccharide is a antioxidants that widely found in natural resources, which is a kind of high molecular polymer with antioxidant activity. It can prevent oxidative stress and play a role in disease prevention through various mechanisms. In this paper, the different types of polysaccharides were summarized, such as plant polysaccharides, algal polysaccharides, microbial polysaccharides and animal polysaccharides, and their antioxidant mechanism and application in the treatment of disease were also discussed. we hope this review can offer some theoretical basis and inspiration for the antioxidant activity study and application of polysaccharides from natural resources.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":"57 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139250907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：