Mona Y Al-Absi, Anna Eleonora Caprifico, Gianpiero Calabrese
The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency in vitro and/or in vivo are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.
{"title":"Chitosan and Its Structural Modifications for siRNA Delivery.","authors":"Mona Y Al-Absi, Anna Eleonora Caprifico, Gianpiero Calabrese","doi":"10.34172/apb.2023.030","DOIUrl":"https://doi.org/10.34172/apb.2023.030","url":null,"abstract":"<p><p>The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency <i>in vitro</i> and/or <i>in vivo</i> are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"275-282"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Javad Ghassemi-Rad, Wasundara Fernando, Bruce E Holbein, David W Hoskin
Purpose: Iron is an essential trace element for the inflammatory response to infection. In this study, we determined the effect of the recently developed iron-binding polymer DIBI on the synthesis of inflammatory mediators by RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) in response to lipopolysaccharide (LPS) stimulation. Methods: Flow cytometry was used to determine the intracellular labile iron pool, reactive oxygen species production, and cell viability. Cytokine production was measured by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Nitric oxide synthesis was determined by the Griess assay. Western blotting was used to assess signal transducer and activator of transcription (STAT) phosphorylation. Results: Macrophages cultured in the presence of DIBI exhibited a rapid and significant reduction in their intracellular labile iron pool. DIBI-treated macrophages showed reduced expression of proinflammatory cytokines interferon-β, interleukin (IL)-1β, and IL-6 in response to LPS. In contrast, exposure to DIBI did not affect LPS-induced expression of tumor necrosis factor-α (TNF-α). The inhibitory effect of DIBI on IL-6 synthesis by LPS-stimulated macrophages was lost when exogenous iron in the form of ferric citrate was added to culture, confirming the selectivity of DIBI for iron. DIBI-treated macrophages showed reduced production of reactive oxygen species and nitric oxide following LPS stimulation. DIBI-treated macrophages also showed a reduction in cytokine-induced activation of STAT 1 and 3, which potentiate LPS-induced inflammatory responses. Conclusion: DIBI-mediated iron withdrawal may be able to blunt the excessive inflammatory response by macrophages in conditions such as systemic inflammatory syndrome.
{"title":"Iron Withdrawal with DIBI, a Novel 3-Hydroxypyridin-4-One Chelator Iron-Binding Polymer, Attenuates Macrophage Inflammatory Responses.","authors":"Javad Ghassemi-Rad, Wasundara Fernando, Bruce E Holbein, David W Hoskin","doi":"10.34172/apb.2023.040","DOIUrl":"https://doi.org/10.34172/apb.2023.040","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Iron is an essential trace element for the inflammatory response to infection. In this study, we determined the effect of the recently developed iron-binding polymer DIBI on the synthesis of inflammatory mediators by RAW 264.7 macrophages and bone marrow-derived macrophages (BMDMs) in response to lipopolysaccharide (LPS) stimulation. <b><i>Methods:</i></b> Flow cytometry was used to determine the intracellular labile iron pool, reactive oxygen species production, and cell viability. Cytokine production was measured by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Nitric oxide synthesis was determined by the Griess assay. Western blotting was used to assess signal transducer and activator of transcription (STAT) phosphorylation. <b><i>Results:</i></b> Macrophages cultured in the presence of DIBI exhibited a rapid and significant reduction in their intracellular labile iron pool. DIBI-treated macrophages showed reduced expression of proinflammatory cytokines interferon-β, interleukin (IL)-1β, and IL-6 in response to LPS. In contrast, exposure to DIBI did not affect LPS-induced expression of tumor necrosis factor-α (TNF-α). The inhibitory effect of DIBI on IL-6 synthesis by LPS-stimulated macrophages was lost when exogenous iron in the form of ferric citrate was added to culture, confirming the selectivity of DIBI for iron. DIBI-treated macrophages showed reduced production of reactive oxygen species and nitric oxide following LPS stimulation. DIBI-treated macrophages also showed a reduction in cytokine-induced activation of STAT 1 and 3, which potentiate LPS-induced inflammatory responses. <b><i>Conclusion:</i></b> DIBI-mediated iron withdrawal may be able to blunt the excessive inflammatory response by macrophages in conditions such as systemic inflammatory syndrome.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"368-377"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose:Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results:In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL1-β) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.
{"title":"Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of <i>Echinacea purpurea</i> (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.","authors":"Fatemeh Mehdizadeh, Ramin Mohammadzadeh, Hossein Nazemiyeh, Mehran Mesgari-Abbasi, Mohammad Barzegar-Jalali, Morteza Eskandani, Khosro Adibkia","doi":"10.34172/apb.2023.031","DOIUrl":"https://doi.org/10.34172/apb.2023.031","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> <i>Echinacea purpurea</i> (L.) Moench is a member of the <i>Asteraceae</i> family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of <i>E. purpurea</i>. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of <i>E. purpurea</i> using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. <b><i>Methods:</i></b> The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. <b><i>Results:</i></b> <i>In vivo</i> studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-β (IL1-β) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (<i>P</i><0.05) whereas other CBC parameters remained unchanged. <b><i>Conclusion:</i></b> The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of <i>E. purpurea</i>.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"283-289"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10086115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.
{"title":"Current and Novel Emerging Medical Therapies for Peripheral Artery Disease: A Literature Review.","authors":"AmirAhmad Arabzadeh, Elnaz Faghfuri, Saiedeh Razi Soofiyani, Elaheh Dalir Abdolahinia, Samaneh Siapush, Kazem Nejati-Koshki, Bita Shahrami, Vahid Asghariazar, Yasamin Pahlavan","doi":"10.34172/apb.2023.025","DOIUrl":"https://doi.org/10.34172/apb.2023.025","url":null,"abstract":"<p><p>Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"259-268"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10086120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: New lethal coronavirus disease 2019 (COVID-19), currently, has been converted to a disastrous pandemic worldwide. As there has been found no definitive treatment for the infection in this review we focused on molecular aspects of coenzyme Q10 (CoQ10) and possible therapeutic potencies of CoQ10 against COVID-19 and similar infections. Methods: This is a narrative review in which we used some authentic resources including PubMed, ISI, Scopus, Science Direct, Cochrane, and some preprint databases, the molecular aspects of CoQ10 effects, regarding to the COVID-19 pathogenesis, have been analyzed and discussed. Results: CoQ10 is an essential cofactor in the electron transport chain of the phosphorylative oxidation system. It is a powerful lipophilic antioxidant, anti-apoptotic, immunomodulatory and anti-inflammatory supplement which has been tested for the management and prevention of a variety of diseases particularly diseases with inflammatory pathogenesis. CoQ10 is a strong anti-inflammatory agent which can reduce tumor necrosis factor-α (TNF-α), interleukin (IL)- 6, C-reactive protein (CRP), and other inflammatory cytokines. The cardio-protective role of CoQ10 in improving viral myocarditis and drug induced cardiotoxicity has been determined in different studies. CoQ10 could also improve the interference in the RAS system caused by COVID-19 through exerting anti-Angiotensin II effects and decreasing oxidative stress. CoQ10 passes easily through blood-brain barrier (BBB). As a neuroprotective agent CoQ10 can reduce oxidative stress and modulate the immunologic reactions. These properties may help to reduce CNS inflammation and prevent BBB damage and neuronal apoptosis in COVID-19 patients. Conclusion: CoQ10 supplementation may prevent the COVID-19-induced morbidities with a potential protective role against the deleterious consequences of the disease, further clinical evaluations are encouraged.
{"title":"Coenzyme Q10 and Its Therapeutic Potencies Against COVID-19 and Other Similar Infections: A Molecular Review.","authors":"Mohammad Fakhrolmobasheri, Mahnaz-Sadat Hosseini, Seyedeh-Ghazal Shahrokh, Zahra Mohammadi, Mohammad-Javad Kahlani, Seyed-Erfan Majidi, Mehrdad Zeinalian","doi":"10.34172/apb.2023.026","DOIUrl":"https://doi.org/10.34172/apb.2023.026","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> New lethal coronavirus disease 2019 (COVID-19), currently, has been converted to a disastrous pandemic worldwide. As there has been found no definitive treatment for the infection in this review we focused on molecular aspects of coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) and possible therapeutic potencies of CoQ<sub>10</sub> against COVID-19 and similar infections. <b><i>Methods:</i></b> This is a narrative review in which we used some authentic resources including PubMed, ISI, Scopus, Science Direct, Cochrane, and some preprint databases, the molecular aspects of CoQ<sub>10</sub> effects, regarding to the COVID-19 pathogenesis, have been analyzed and discussed. <b><i>Results:</i></b> CoQ<sub>10</sub> is an essential cofactor in the electron transport chain of the phosphorylative oxidation system. It is a powerful lipophilic antioxidant, anti-apoptotic, immunomodulatory and anti-inflammatory supplement which has been tested for the management and prevention of a variety of diseases particularly diseases with inflammatory pathogenesis. CoQ<sub>10</sub> is a strong anti-inflammatory agent which can reduce tumor necrosis factor-α (TNF-α), interleukin (IL)- 6, C-reactive protein (CRP), and other inflammatory cytokines. The cardio-protective role of CoQ<sub>10</sub> in improving viral myocarditis and drug induced cardiotoxicity has been determined in different studies. CoQ<sub>10</sub> could also improve the interference in the RAS system caused by COVID-19 through exerting anti-Angiotensin II effects and decreasing oxidative stress. CoQ<sub>10</sub> passes easily through blood-brain barrier (BBB). As a neuroprotective agent CoQ<sub>10</sub> can reduce oxidative stress and modulate the immunologic reactions. These properties may help to reduce CNS inflammation and prevent BBB damage and neuronal apoptosis in COVID-19 patients. <b><i>Conclusion:</i></b> CoQ<sub>10</sub> supplementation may prevent the COVID-19-induced morbidities with a potential protective role against the deleterious consequences of the disease, further clinical evaluations are encouraged.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"233-243"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9764065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Magnetic hyperthermia is a treatment method based on eddy currents, hysteresis, and relaxation mechanisms of magnetic nanoparticles (MNPs). MNPs such as Fe3 O4 have the ability to generate heat under an alternating magnetic field. Heat sensitive liposomes (Lip) convert from lipid layer to liquid layer through heat generated by MNPs and can release drugs. Methods: In this study, different groups of doxorubicin (DOX), MNPs and liposomes were evaluated. The MNPs were synthesized by co-precipitation method. The MNPs, DOX and a combination of MNPs and DOX were efficiently loaded into the liposomes using the evaporator rotary technique. Magnetic properties, microstructure, specific absorption rate (SAR), zeta potential, loading percentage of the MNPs and DOX concentration in liposomes, in vitro drug release of liposomes were studied. Finally, the necrosis percentage of cancer cells in C57BL/6J mice bearing melanoma tumors was assessed for all groups. Results: The loading percentages of MNPs and concentration of DOX in the liposomes were 18.52 and 65% respectively. The Lip-DOX-MNPs at the buffer citrate solution, showed highly SAR as the solution temperature reached 42°C in 5 minutes. The release of DOX occurred in a pH-dependent manner. The volume of tumor in the therapeutic groups containing the MNPs significantly decreased compared to the others. Numerical analysis showed that the tumor volume in mice receiving Lip-MNPs-DOX was 9.29% that of the control and a histological examination of the tumor section showed 70% necrosis. Conclusion: The Lip-DOX-MNPs could be effective agents which reduce malignant skin tumors growth and increase cancer cell necrosis.
{"title":"Liposome-Fe<sub>3</sub> O<sub>4</sub>-Doxorubicin Mediated Treatment of Melanoma Tumors.","authors":"Azalia Azlegini, Sirus Javadpour, Mohamad Ebrahim Bahrololoom","doi":"10.34172/apb.2023.034","DOIUrl":"https://doi.org/10.34172/apb.2023.034","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Magnetic hyperthermia is a treatment method based on eddy currents, hysteresis, and relaxation mechanisms of magnetic nanoparticles (MNPs). MNPs such as Fe<sub>3</sub> O<sub>4</sub> have the ability to generate heat under an alternating magnetic field. Heat sensitive liposomes (Lip) convert from lipid layer to liquid layer through heat generated by MNPs and can release drugs. <b><i>Methods:</i></b> In this study, different groups of doxorubicin (DOX), MNPs and liposomes were evaluated. The MNPs were synthesized by co-precipitation method. The MNPs, DOX and a combination of MNPs and DOX were efficiently loaded into the liposomes using the evaporator rotary technique. Magnetic properties, microstructure, specific absorption rate (SAR), zeta potential, loading percentage of the MNPs and DOX concentration in liposomes, in vitro drug release of liposomes were studied. Finally, the necrosis percentage of cancer cells in C57BL/6J mice bearing melanoma tumors was assessed for all groups. <b><i>Results:</i></b> The loading percentages of MNPs and concentration of DOX in the liposomes were 18.52 and 65% respectively. The Lip-DOX-MNPs at the buffer citrate solution, showed highly SAR as the solution temperature reached 42°C in 5 minutes. The release of DOX occurred in a pH-dependent manner. The volume of tumor in the therapeutic groups containing the MNPs significantly decreased compared to the others. Numerical analysis showed that the tumor volume in mice receiving Lip-MNPs-DOX was 9.29% that of the control and a histological examination of the tumor section showed 70% necrosis. <b><i>Conclusion:</i></b> The Lip-DOX-MNPs could be effective agents which reduce malignant skin tumors growth and increase cancer cell necrosis.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"309-316"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9709998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan
Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).
{"title":"The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran.","authors":"Elaheh Jabbari Hagh, Ali Mousavi, Seyyedeh Mina Hejazian, Mehdi Haghi, Samaneh Esfahanian, Elham Ahmadian, Sepideh Zununi Vahed, Mohammadreza Ardalan","doi":"10.34172/apb.2023.038","DOIUrl":"https://doi.org/10.34172/apb.2023.038","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. <b><i>Methods:</i></b> Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. <b><i>Results:</i></b> Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote <i>CYP3A5 *3/*</i>3 carriers (<i>P</i>=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (<i>P</i>>0.05). <b><i>Conclusion:</i></b> Homozygote <i>CYP3A5 *3/*</i>3 genotype could influence the tacrolimus metabolism rate (C/D ratio).</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 2","pages":"393-398"},"PeriodicalIF":3.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
One of the central signaling pathways with a regulatory effect on cell proliferation and survival is Akt/mTOR. In many human cancer types, for instance, lung cancer, the overexpression of Akt/mTOR has been reported. For this reason, either targeting cancer cells by synthetic or natural products affecting the Akt/mTOR pathway down-regulation is a useful strategy in cancer therapy. Direct inhibition of the signaling pathway or modulation of each related molecule could have significant feedback on the growth and proliferation of cancer cells. A variety of secondary metabolites has been identified to directly inhibit the AKT/mTOR signaling, which is important in the field of drug discovery. Naturally occurring nitrogenous and phenolic compounds can emerge as two pivotal classes of natural products possessing anticancer abilities. Herein, we have summarized the alkaloids and flavonoids for lung cancer treatment together with all the possible mechanisms of action relying on the Akt/mTOR pathway down-regulation. This review suggested that in search of new drugs, phytochemicals could be considered as promising scaffolds to be developed into efficient drugs for the treatment of cancer. In this review, the terms "Akt/mTOR", "Alkaloid", "flavonoid", and "lung cancer" were searched without any limitation in search criteria in Scopus, PubMed, Web of Science, and Google scholar engines.
Akt/mTOR是调控细胞增殖和存活的主要信号通路之一。在许多人类癌症类型中,例如肺癌,Akt/mTOR的过度表达已被报道。因此,通过影响Akt/mTOR通路下调的合成或天然产物靶向癌细胞是一种有效的癌症治疗策略。直接抑制信号通路或调节各相关分子对癌细胞的生长和增殖有显著的反馈作用。多种次生代谢物可直接抑制AKT/mTOR信号传导,这在药物研发领域具有重要意义。天然存在的氮化合物和酚类化合物可以作为具有抗癌能力的两类关键天然产物出现。在此,我们总结了生物碱和黄酮类化合物治疗肺癌的作用,以及依赖于Akt/mTOR通路下调的所有可能的作用机制。这一综述表明,在寻找新的药物的过程中,植物化学物质可以被认为是一个有前途的支架,可以开发成有效的治疗癌症的药物。在本文中,我们在Scopus、PubMed、Web of Science和Google学术搜索引擎中对“Akt/mTOR”、“Alkaloid”、“flavonoids”和“lung cancer”等关键词进行了检索,检索条件不受任何限制。
{"title":"Bioactive PI3-kinase/Akt/mTOR Inhibitors in Targeted Lung Cancer Therapy.","authors":"Somayyeh Ghareghomi, Vahideh Atabaki, Naseh Abdollahzadeh, Shahin Ahmadian, Salar Hafez Ghoran","doi":"10.34172/apb.2023.003","DOIUrl":"https://doi.org/10.34172/apb.2023.003","url":null,"abstract":"<p><p>One of the central signaling pathways with a regulatory effect on cell proliferation and survival is Akt/mTOR. In many human cancer types, for instance, lung cancer, the overexpression of Akt/mTOR has been reported. For this reason, either targeting cancer cells by synthetic or natural products affecting the Akt/mTOR pathway down-regulation is a useful strategy in cancer therapy. Direct inhibition of the signaling pathway or modulation of each related molecule could have significant feedback on the growth and proliferation of cancer cells. A variety of secondary metabolites has been identified to directly inhibit the AKT/mTOR signaling, which is important in the field of drug discovery. Naturally occurring nitrogenous and phenolic compounds can emerge as two pivotal classes of natural products possessing anticancer abilities. Herein, we have summarized the alkaloids and flavonoids for lung cancer treatment together with all the possible mechanisms of action relying on the Akt/mTOR pathway down-regulation. This review suggested that in search of new drugs, phytochemicals could be considered as promising scaffolds to be developed into efficient drugs for the treatment of cancer. In this review, the terms \"Akt/mTOR\", \"Alkaloid\", \"flavonoid\", and \"lung cancer\" were searched without any limitation in search criteria in Scopus, PubMed, Web of Science, and Google scholar engines.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 1","pages":"24-35"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leandra de Almeida Ribeiro Oliveira, Arthur Christian Garcia da Silva, Douglas Vieira Thomaz, Fabiana Brandão, Edemilson Cardoso da Conceição, Marize Campos Valadares, Maria Tereza Freitas Bara, Dâmaris Silveira
Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In this study, the mechanisms underlying the anti-inflammatory activity of P. emarginatus oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. Results: Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin 6 (IL-6) was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. Conclusion: The results support the ethnomedicinal use of P. emarginatus oleoresin as an anti-inflammatory herbal medicine, and also highlight P. emarginatus oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, cyclooxygenase-2 (COX-2), phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.
{"title":"The Potential of Vouacapanes from <i>Pterodon emarginatus</i> Vogel Against COVID-19 Cytokine Storm.","authors":"Leandra de Almeida Ribeiro Oliveira, Arthur Christian Garcia da Silva, Douglas Vieira Thomaz, Fabiana Brandão, Edemilson Cardoso da Conceição, Marize Campos Valadares, Maria Tereza Freitas Bara, Dâmaris Silveira","doi":"10.34172/apb.2023.016","DOIUrl":"https://doi.org/10.34172/apb.2023.016","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of <i>Pterodon emarginatus</i> Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven <i>in vivo, in vitro</i>, and <i>in silico</i>. Therefore, the aim of this work is to evaluate <i>P. emarginatus</i> oleoresin and isolated diterpenes by <i>in vitro</i> anti-inflammatory models. <b><i>Methods:</i></b> In this study, the mechanisms underlying the anti-inflammatory activity of <i>P. emarginatus</i> oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. <b><i>Results:</i></b> Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin 6 (IL-6) was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. <b><i>Conclusion:</i></b> The results support the ethnomedicinal use of <i>P. emarginatus</i> oleoresin as an anti-inflammatory herbal medicine, and also highlight <i>P. emarginatus</i> oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, cyclooxygenase-2 (COX-2), phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 1","pages":"150-159"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ata Mahmoodpoor, Afsaneh Farjami, Niloufar Farzan, Hamed Hamishehkar, Parina Asgharian, Sarvin Sanaie, Kamran Shadvar, Farnaz Naeimzadeh, Hadi Hamishehkar
Purpose: Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. Methods: In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. Results: Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (P<0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. Conclusion: In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.
{"title":"Taurine in Septic Critically Ill Patients: Plasma versus Blood.","authors":"Ata Mahmoodpoor, Afsaneh Farjami, Niloufar Farzan, Hamed Hamishehkar, Parina Asgharian, Sarvin Sanaie, Kamran Shadvar, Farnaz Naeimzadeh, Hadi Hamishehkar","doi":"10.34172/apb.2023.015","DOIUrl":"https://doi.org/10.34172/apb.2023.015","url":null,"abstract":"<p><p><b><i>Purpose:</i></b> Sepsis and systemic inflammatory response syndrome (SIRS) encompass various problems throughout the body, and two of its major problems are the creation of oxidative substances in the body and decrease of the body's antioxidant capacity to deal with the stress and organ damage. Optimal enteral nutrition fortified with antioxidant or immunomodulator amino acid is a hot topic concerning sepsis in the critical care setting. Taurine plays a protective role as an antioxidant in cells that is likely to have a protective role in inflammation and cytotoxicity. <b><i>Methods:</i></b> In the present study, 20 septic patients and 20 healthy volunteers were enrolled. The blood and plasma taurine levels of the patients on days 1, 3 and 7 were measured. Blood and plasma taurine level and the correlation between them, organ failure, and severity of the disease were assessed. <b><i>Results:</i></b> Taurine concentrations in the plasma of the septic patients were significantly lower than control group, and the whole blood concentrations were significantly higher than those of the control group (<i>P</i><0.001). There was not a significant correlation between the blood and plasma taurine levels in control and septic patients. In addition, there was not any correlation between the severity of the disease, organ failure, mortality, and plasma as well as the blood concentration of taurine. <b><i>Conclusion:</i></b> In septic patients, taurine concentration in plasma and blood are low and high, respectively. These concentrations are not linked to each other and not associated with the patients' outcome, and the disease severity, and organ failure.</p>","PeriodicalId":7256,"journal":{"name":"Advanced pharmaceutical bulletin","volume":"13 1","pages":"143-149"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}