Iranian Journal of Pharmaceutical Research最新文献

{"title":"C-Phycocyanin and Phycocyanobilin as a Novel Adjuvant in Hepatitis B Vaccine.","authors":"Nargess Abdali, Reza Tabaripour, Solaleh Javadi, Mehrab Nasirikenari, Mehdi Birjandi, Vahid Siavashi, Mohammad Reza Naghavi, Zahra Hasani, Ali Ahmari, Hossein Hanifi","doi":"10.5812/ijpr-147060","DOIUrl":"https://doi.org/10.5812/ijpr-147060","url":null,"abstract":"<p><strong>Background: </strong>Vaccine adjuvants are components that enhance immune responses to an antigen. Given the importance of adjuvants, research on novel adjuvants with higher efficacy and fewer adverse effects remains crucial. <i>Spirulina</i> (<i>Arthrospira</i> sp.), an aqueous, photosynthetic, filamentous, spiral, multicellular microalga also classified as a cyanobacterium, is well known for its high protein content, vitamins, essential fatty acids, and amino acids. C-phycocyanin (C-PC) is one of the most significant proteins in <i>Spirulina</i>.</p><p><strong>Objectives: </strong>This study aimed to investigate the adjuvant capabilities of three <i>Spirulina</i>-derived substances-<i>Spirulina</i> extract, C-phycocyanin (C-PC), and phycocyanobilin (PCB)-in conjunction with the Hepatitis B surface antigen (HBsAg).</p><p><strong>Methods: </strong>Vaccine groups received the vaccine and adjuvants three times at two-week intervals, administered either orally or by injection in encapsulated or naked forms. To use the injectable form while preventing antigenic effects from the C-PC protein portion, the PCB portion was isolated and used as an injectable adjuvant.</p><p><strong>Results: </strong>The highest levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) stimulation were observed in the naked PCB form with the vaccine. In both oral and injectable forms of PCB and C-PC, results indicated an increased expression of Hepatitis B surface antibodies (HBsAb) in response to the antigen. The absence of a significant difference between C-PC and <i>Spirulina</i> extract in oral form suggested that the adjuvant effect of this microalga was primarily due to the C-PC compound. Additionally, the injectable form of PCB led to the highest HBsAb expression level. This enhancement of the humoral immune response indicated that these compounds have potential as adjuvants in both oral and injectable forms.</p><p><strong>Conclusions: </strong>These findings suggest the potential for improved Hepatitis B vaccine efficacy with this novel adjuvant, paving the way for further evaluation with other vaccines.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147060"},"PeriodicalIF":1.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The COVID-19 Pandemic and the Resilience of the Pharmaceutical Supply Chain: Lessons from Past Experiences and Strategies for the Future.","authors":"Mohamad Ali Aivazi, Hamid Reza Rasekh, Mohammad Peikanpour, Farzad Peiravian, Sajjad Esmaeili, Leila Zarei","doi":"10.5812/ijpr-152723","DOIUrl":"https://doi.org/10.5812/ijpr-152723","url":null,"abstract":"<p><strong>Background: </strong>The pharmaceutical supply chain (PSC) faced numerous challenges, particularly during the COVID-19 crisis. Due to the supply chain (SC) 's vulnerabilities, it requires enhanced capabilities to address these challenges. In Iran, specific economic and political issues have intensified the vulnerabilities of the PSC.</p><p><strong>Objectives: </strong>This study investigates the issues caused by the COVID-19 crisis in the PSC, identifies and characterizes these issues, and recommends appropriate courses of action to address future SC disruptions.</p><p><strong>Methods: </strong>This study is a qualitative-quantitative analysis conducted in Iran during the COVID-19 crisis. Qualitative thematic analysis was performed from July 2022 until May 2023. Semi-structured, in-depth, face-to-face interviews with 23 Iranian PSC specialists were conducted until saturation was reached. The qualitative phase was analyzed using MAXQDA 2021. The quantitative phase included a survey of 547 individuals working in pharmaceutical manufacturing in Iran, with the questionnaires analyzed using SPSS 26.</p><p><strong>Results: </strong>In the qualitative phase, the research identified two main themes: (1) vulnerabilities and (2) capabilities, along with 15 subthemes providing solutions to enhance the resilience of the PSC. In the quantitative phase, findings from 64 questionnaires highlighted major vulnerabilities and capabilities necessary to create a resilient SC. The median score for vulnerabilities was 5.12, while the median score for capabilities was 5.39.</p><p><strong>Conclusions: </strong>According to the questionnaire results, the quantitative findings indicate that capabilities received a higher score, suggesting that this sector of the PSC demonstrated better resilience against the pandemic. This study, with its contextual focus, mixed-method approach, comprehensive analysis of vulnerabilities and capabilities, and sector-specific insights, offers a novel contribution to the understanding of SC resilience within Iranian pharmaceutical manufacturing. It also has the potential to promote further research in other sectors of the PSC.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e152723"},"PeriodicalIF":1.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin-Etoposide Synergy: Unveiling the Molecular Mechanisms of Enhanced Apoptosis and Chemoresistance Attenuation in Breast Cancer.","authors":"Bahar Jaberian Asl, Reza Afarin, Mahdi Hatami, Amineh Dehghani Madiseh, Mohammadreza Roshanazadeh, Mojtaba Rashidi","doi":"10.5812/ijpr-150978","DOIUrl":"https://doi.org/10.5812/ijpr-150978","url":null,"abstract":"<p><strong>Background: </strong>Combining natural compounds with chemotherapeutic agents has emerged as a promising approach for cancer treatment. Curcumin (Cur), a natural polyphenol, is known for its anti-cancer properties, including the ability to induce apoptosis and arrest cell cycle progression.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effects of Cur and etoposide (ETO), both individually and in combination, on the induction of apoptosis in breast cancer (BC) cell lines.</p><p><strong>Methods: </strong>The impact of Cur and ETO on cell proliferation was assessed using MTT viability assays. Apoptosis induction by these drugs was evaluated through Annexin V flow cytometry and caspase-3 and caspase-9 activity assays. Quantitative real-time PCR was employed to measure Bax and Bcl-2 gene expression levels. Western blotting was conducted to determine protein levels of p53, p21, Bax, and Bcl-2.</p><p><strong>Results: </strong>A non-significant dose of ETO was selected based on MTT assay results and combined with 75 µM of Cur. Curcumin enhanced ETO's pro-apoptotic effect by increasing caspase activities. The combination of Cur and ETO significantly reduced Bcl-2 gene expression while upregulating Bax expression. Furthermore, treatment with this combination elevated the protein levels of p53, p21, and Bax, compared to ETO or Cur alone, while significantly decreasing Bcl-2 protein levels.</p><p><strong>Conclusions: </strong>Cur has the potential to amplify ETO-induced apoptosis in BC cells. This combination may offer a promising therapeutic approach for BC.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150978"},"PeriodicalIF":1.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review.","authors":"Mobina Tajdari, Amirreza Peyrovinasab, Maryam Bayanati, Mohammad Ismail Mahboubi Rabbani, Amir Hossein Abdolghaffari, Afshin Zarghi","doi":"10.5812/ijpr-151312","DOIUrl":"https://doi.org/10.5812/ijpr-151312","url":null,"abstract":"<p><p>Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the COX-2/PGE2 axis. Therefore, suppressing COX activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. This review explores the mechanisms of TNF-α-induced COX-2/PGE2 expression, a significant pathophysiological feature of cancer development. Furthermore, we summarize chemical compounds with dual COX-2/TNF-α inhibitory actions, providing an overview of their structure-activity relationship. These insights may contribute to the development of new generations of dual-acting COX-2/TNF-α inhibitors with enhanced efficacy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e151312"},"PeriodicalIF":1.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Clindamycin in Preventing Abortion and Vertical Transmission of <i>Toxoplasma gondii</i> (PRU Strain) Infection in Pregnant BALB/c Mice.","authors":"Mitra Sadeghi, Seyed Abdollah Hosseini, Shahabeddin Sarvi, Pedram Ebrahimnejad, Hossein Asgarian Omran, Zohreh Zare, Shirzad Gholami, Alireza Khalilian, Mostafa Tork, Ahmad Daryani, Sargis A Aghayan","doi":"10.5812/ijpr-150424","DOIUrl":"https://doi.org/10.5812/ijpr-150424","url":null,"abstract":"<p><strong>Background: </strong><i>Toxoplasma gondii</i> transmission can occur during pregnancy if the mother contracts the infection for the first time. Treatment strategies include the use of antimicrobial medications and providing supportive care. Spiramycin is commonly used to treat toxoplasmosis in pregnant women and to hinder the disease's transmission. However, its ability to treat the fetus is questionable due to its limited capacity to cross the placental barrier. Additionally, economic constraints and sanctions may impede access to this medication.</p><p><strong>Objectives: </strong>Consequently, in search of an effective treatment, for the first time in Iran, the effectiveness of clindamycin in preventing abortion and vertical transmission of the PRU strain of <i>T. gondii</i> infection in pregnant mice was evaluated.</p><p><strong>Methods: </strong>On the twelfth day of gestation, pregnant mice were exposed to <i>T. gondii</i> and subsequently received treatment with either clindamycin or spiramycin. This resulted in the establishment of four distinct groups: A normal control group, an infected group without treatment, an infected group treated with clindamycin, and another infected group treated with spiramycin. Following these interventions, a series of parasitological evaluations (including microscopic examination and real-time PCR), histopathological evaluations, and immunological assessments were conducted.</p><p><strong>Results: </strong>The findings showed a significant reduction in the number of cysts in the eye and brain (ranging from 77.32% to 90.72%) among the groups treated with clindamycin and spiramycin compared to the control group. Furthermore, treatment with clindamycin, like treatment with spiramycin, was able to suppress inflammatory changes, prevent cell death, and reduce vascular cuffs in the brain, as well as decrease bleeding, placental thrombosis, and the accumulation of inflammatory cells in the placenta. Clindamycin was also effective in diminishing retinal folds, tiny retinal bleeds, and cell vacuolation in eye tissues. Immunologically, treatment in both the spiramycin and clindamycin groups resulted in a decrease in the level of the cytokine TNF-α, indicating an increase in the cellular immune response. In addition, increased levels of IL-10 in the treated infected groups could contribute to the reduction of TNF-α production.</p><p><strong>Conclusions: </strong>Typically, spiramycin is the first choice for treating congenital toxoplasmosis, but clindamycin can be a useful substitute or additional treatment when resistance to primary medications occurs, when there is intolerance, or when access to the main drugs is restricted.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150424"},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendrosomal Curcumin Showed Cytotoxic Effects on Breast Cancer Cell Line by Inducing Mitochondrial Apoptosis Pathway and Cell Division Arrest.","authors":"Houriye Abbasi, Fatemeh Hosseinkhani, Bahareh Imani Fouladi, Siroos Tarighi, Majid Sadeghizadeh, Maryam Montazeri","doi":"10.5812/ijpr-151714","DOIUrl":"https://doi.org/10.5812/ijpr-151714","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the <i>p53 gene</i> have been linked to the initiation and progression of breast cancer, as well as resistance to chemotherapy. Therefore, the development of novel treatment approaches is essential to combat this disease.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effects of dendrosomal curcumin (DNC) on the breast cancer cell line MDA-MB231.</p><p><strong>Methods: </strong>MDA-MB231 cells were treated with 20 μM DNC, and the apoptosis rate and cell proliferation cycles were assessed using flow cytometry. Additionally, after RNA extraction and cDNA synthesis, the expression levels of <i>Lnc-DANCR</i>, <i>EZH2</i>, <i>Noxa</i>, <i>bcl-2</i>, <i>bax</i>, <i>PUMA</i>, <i>p21</i>, and <i>p53 gene</i>s were analyzed using RT-PCR. Protein expression levels of <i>P53</i>, <i>P21</i>, <i>Bcl-2</i>, and <i>Bax</i> were evaluated through western blotting.</p><p><strong>Results: </strong>Dendrosomal curcumin induced apoptosis in MDA-MB231 cells and caused cell cycle arrest at the SubG1 phase. Dendrosomal curcumin treatment downregulated <i>Lnc-DANCR</i>, <i>EZH2</i>, <i>bcl-2</i>, and <i>p53 gene</i> expression, while upregulating <i>bax</i>, <i>Noxa</i>, <i>PUMA</i>, and <i>p21</i> gene expression in a time-dependent manner. <i>Bax</i> and <i>P21</i> protein levels were significantly upregulated following DNC treatment, whereas <i>Bcl-2</i> and <i>P53</i> protein levels were downregulated in DNC-treated breast cancer cells.</p><p><strong>Conclusions: </strong>In summary, dendrosomal nanocurcumin demonstrated potent anti-tumor effects against breast cancer cells, suggesting its potential as a therapeutic agent in breast cancer treatment.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e151714"},"PeriodicalIF":1.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of Aminoguanidine, Semicarbazide and Thiosemicarbazide Treatment for Methylglyoxal-Induced Neurological Toxicity in Experimental Models.","authors":"Noushin Nikray, Nikoo Abharian, Shahin Jafari Ashtiani, Farzad Kobarfard, Mehrdad Faizi","doi":"10.5812/ijpr-153322","DOIUrl":"https://doi.org/10.5812/ijpr-153322","url":null,"abstract":"<p><strong>Background: </strong>Advanced glycation end products (AGEs) are complex compounds that play a critical role in neurological disorders, including the pathogenesis of Alzheimer's disease. Methylglyoxal (MG) is recognized as the primary precursor of AGEs. Methylglyoxal is produced endogenously and also introduced through dietary exposures.</p><p><strong>Objectives: </strong>This study aimed to investigate and compare the effects of aminoguanidine (AG), semicarbazide (SC), and thiosemicarbazide (TSC) on MG-induced neurological toxicity in rats.</p><p><strong>Methods: </strong>Male Wistar rats were exposed orally to MG, MG + AG, MG + SC, and MG + TSC for 70 days. Neurobehavioral, biochemical, and histopathological changes were evaluated.</p><p><strong>Results: </strong>The findings indicated that oral administration of MG for 70 days resulted in memory impairment and increased anxiety in neurobehavioral tests. Additionally, MG elevated protein carbonylation in brain tissues. Semicarbazide was found to prevent MG-induced memory problems, while both SC and AG reduced carbonyl content in brain tissues. Aminoguanidine and TSC were effective in alleviating anxiety induced by MG exposure. Histopathological analysis revealed that MG caused cell damage and neuronal necrosis in the hippocampus, particularly in the cornu ammonis 1 and 3 (CA1 and CA3) and AG, SC, and TSC improved neuronal survival specifically in the CA1 and DG areas.</p><p><strong>Conclusions: </strong>The data suggest that SC, AG, and TSC may offer neuroprotective effects against MG-induced neurobehavioral toxicity. Further studies are required to explore the mechanisms of action of these compounds.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e153322"},"PeriodicalIF":1.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Interaction of Chloroquine with <i>Artemisia kopetdaghensis</i> Semipolar Extract Against <i>Plasmodium berghei</i>: Histopathological and Immunological Studies in a Mouse Model.","authors":"Roya Amirian, Mustafa Ghanadian, Hamed Fouladseresht, Azar Baradaran, Seyed Mohammad Abtahi, Bahareh Basirpour, Maryam Fattahian, Seyed Mahmoud Mousavi, Parastoo Hassani-Abharian, Hajar Shabandoust, Seyedamirmehdi Hejazi Dehaghani, Seyed Hossein Hejazi","doi":"10.5812/ijpr-147234","DOIUrl":"https://doi.org/10.5812/ijpr-147234","url":null,"abstract":"<p><strong>Background: </strong>Malaria parasites have gradually developed resistance to commonly used antimalarial drugs. For decades, chloroquine was the most widely used drug to eradicate malaria. However, with the spread of chloroquine resistance, many countries have adopted combination therapies that utilize two drugs acting synergistically instead of monotherapy. In this study, the synergistic effect of chloroquine and the semipolar extract of <i>Artemisia kopetdaghensis</i>. Semipolar extract (SPE) was investigated in vivo through pathological and parasitological studies on mouse model.</p><p><strong>Methods: </strong>Sixty female Balb/c mice infected with the <i>Plasmodium berghei</i> (<i>P. berghei</i>) parasite were treated with different concentrations of the semipolar extract of <i>Artemisia kopetdaghensis</i> (SPE) according to the protocol. The mean percentage of parasitemia, the mean survival time of the mice, the serum levels of IFN-γ, IL-4, IL-17, and TGF-β, and the effects of the SPE on the kidney, spleen, and liver tissues were investigated and compared across different treatment groups. The data were analyzed using Bonferroni, ANOVA, and Tukey tests.</p><p><strong>Results: </strong>The semipolar extract of <i>Artemisia kopetdaghensis</i> (SPE) demonstrated better therapeutic effects in both synergistic and monotherapy conditions compared to chloroquine alone. The combination of chloroquine and SPE resulted in the lowest parasitemia rate, the highest percentage of parasite inhibition, and the longest average survival time. Pathological studies showed no signs of acute toxicity in the organs.</p><p><strong>Conclusions: </strong>This study demonstrated that using chloroquine in combination with <i>Artemisia kopetdaghensis</i> semipolar extract has synergistic effects in reducing parasitemia, enhancing the inhibitory effect on parasite growth and reproduction, and balancing the host immune system.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147234"},"PeriodicalIF":1.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"24-Dehydrocholesterol Reductase Facilitates Cisplatin Resistance of Non-small Cell Lung Cancer via Repressing Reactive Oxygen Species/Ferroptosis Pathway.","authors":"Ce Qin, Jun Yuan, Rui Zhang, Li Liu, Yue-Song Ban","doi":"10.5812/ijpr-150017","DOIUrl":"https://doi.org/10.5812/ijpr-150017","url":null,"abstract":"<p><strong>Background: </strong>Non-small-cell lung cancer (NSCLC) remains a deadly malignancy worldwide. Resistance to cisplatin (DDP) is a significant obstacle that limits the therapeutic efficacy in NSCLC patients.</p><p><strong>Objectives: </strong>This study investigated the role and mechanism of 24-dehydrocholesterol reductase (DHCR24) in DDP resistance in NSCLC cells.</p><p><strong>Methods: </strong>24-dehydrocholesterol reductase levels, ferroptosis-related molecules, and proteins involved in the PI3K/AKT/GSK3β pathway were measured. The growth capacity of the cells was evaluated, and ferroptosis was assessed by measuring MDA, GSH, Fe²⁺, and ROS levels. The impact of DHCR24 on NSCLC DDP resistance was analyzed using a tumor xenograft assay in vivo. Ki-67 and DHCR24 expression in tumors were evaluated through immunohistochemical staining.</p><p><strong>Results: </strong>24-dehydrocholesterol reductase expression was elevated in DDP-resistant cells, indicating a poorer prognosis for NSCLC patients. Down-regulation of DHCR24 inhibited the growth of DDP-resistant cells and induced ferroptosis. Inhibition of DHCR24 led to the inactivation of the PI3K/AKT/GSK3β pathway and subsequent induction of ferroptosis. Inhibition of ferroptosis or activation of the PI3K/AKT/GSK3β pathway counteracted the increased DDP sensitivity induced by DHCR24 knockdown in NSCLC cells. Additionally, DHCR24 deficiency improved NSCLC DDP resistance in vivo.</p><p><strong>Conclusions: </strong>24-dehydrocholesterol reductase contributes to DDP resistance in NSCLC cells by suppressing ferroptosis through the activation of the PI3K/AKT/GSK3β pathway.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150017"},"PeriodicalIF":1.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Weight Indices and Blood Levels of Immunosuppressive Drugs in Renal Transplant Recipients.","authors":"Shirinsadat Badri, Bozorgmehr Dadkhah-Tehrani, Abdolamir Atapour, Shahrzad Shahidi, Mojgan Mortazavi, Tahereh Gholipourshahraki","doi":"10.5812/ijpr-146619","DOIUrl":"https://doi.org/10.5812/ijpr-146619","url":null,"abstract":"<p><strong>Background: </strong>Calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors are essential for maintaining transplanted organs. However, determining the appropriate dosage and predicting blood concentrations of these drugs based solely on net body weight may be inadequate. Previous studies have presented contradictory results regarding the impact of obesity on drug concentrations and transplant success.</p><p><strong>Objectives: </strong>This study aims to evaluate various weight indices to identify the most reliable indicator of weight that correlates with the blood levels of drugs used in organ transplantation.</p><p><strong>Methods: </strong>This retrospective descriptive study included patients from nephrology clinics affiliated with Isfahan University of Medical Sciences who were taking calcineurin and/or mTOR inhibitor drugs. Data extracted from medical records included demographic and clinical information, such as height, weight, and various weight indices (total/ideal/adjusted body weight, lean body mass (LBM), Body Mass Index, and predicted normal weight), as well as blood levels of immunosuppressive drugs at each patient's visit. The dosages of each drug (mg/kg) were analyzed to determine which weight indices best correlated with the obtained blood concentrations, using the Generalized Estimating Equation (GEE) model with logistic regression, an independent correlation matrix, and a binary distribution for data analysis.</p><p><strong>Results: </strong>The study analyzed the medical records of 71 patients. Trough (C0) concentrations of drugs were evaluated in relation to each weight index, and odds ratios (OR) were calculated for statistical comparison. All weight indices increased the likelihood of achieving appropriate concentrations for cyclosporine, tacrolimus, and sirolimus. Drug dosing based on LBM (OR: 1.028), ideal body weight (OR: 1.075), and total body weight (OR: 1.041) showed the strongest correlations with achieving proper blood levels for cyclosporine, tacrolimus, and sirolimus, respectively.</p><p><strong>Conclusions: </strong>Integrating various weight indices for calculating individualized doses (mg/kg) of each immunosuppressive drug increases the likelihood of achieving appropriate blood concentrations. However, the optimal weight index varies for each drug. Further studies, particularly those incorporating therapeutic drug monitoring (TDM) plans in transplant centers, are warranted to validate and generalize these findings, providing a potential avenue for improving immunosuppressive therapy and enhancing transplant outcomes.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e146619"},"PeriodicalIF":1.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}