Research in Pharmaceutical Sciences最新文献

{"title":"<i>In vitro</i> and <i>in vivo</i> evaluation of anti-inflammatory activities of ethanol extract from Lom-Am-Ma-Pruek remedy for pain relief.","authors":"Arunporn Itharat, Pun Thongmee, Krit Piwngam, Janjira Inprasit, Sunita Makchuchit, Pranporn Kuropakornpong, Neal M Davies","doi":"10.4103/RPS.RPS_26_24","DOIUrl":"10.4103/RPS.RPS_26_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Lom-Am-Ma-Pruek (LAMP) remedy has been used in Thai traditional medicine to relieve pain associated with the inflammatory process. The anti-inflammatory activity and bioactivity of LAMP in an animal model have not been previously investigated. We evaluated the <i>in-vitro</i> and <i>in-vivo</i> anti-inflammatory activity of LAMP ethanol extract.</p><p><strong>Experimental approach: </strong>The anti-inflammatory activity of LAMP and its plant ingredients were investigated on lipopolysaccharide-stimulated NO, PGE2, and TNF-α release from RAW264.7 cells. Furthermore, the stability of LAMP under biological and chemical accelerated conditions was evaluated using the Griess reaction assay and HPLC. Lastly, rat models with ethyl phenylpropionate (EPP)-induced ear edema and carrageenan-induced paw edema were utilized to assess anti-inflammatory activity.</p><p><strong>Findings/results: </strong>LAMP possessed potent inhibitory effects on NO, PGE2, and TNF-α production with IC50 values of 24.90 ± 0.86, 4.77 ± 0.03, and 35.01 ± 2.61 µg/mL, respectively. In addition, LAMP extract demonstrated stable biological activity, anti-inflammatory effects, and phytochemical content stability under stress conditions. Additionally, 0.5%, 1%, and 2% w/v LAMP significantly inhibited EPP-induced rat ear edema over time equivalent to 5% w/v phenylbutazone. LAMP at 180, 375, and 750 mg/kg also considerably reduced carrageenan-induced rat paw edema 2 h after carrageenan administration compared to phenylbutazone at 250 mg/kg.</p><p><strong>Conclusion and implications: </strong>LAMP has anti-inflammatory activity by inhibiting PGE2 formation. These findings are consistent with the efficacy and traditional use of the LAMP remedy in treating inflammatory diseases.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"683-697"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256594","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}

{"title":"Synthesis, docking, pharmacokinetic prediction, and acetylcholinesterase inhibitory evaluation of <i>N</i>-(2-(piperidine-1-yl)ethyl)benzamide derivatives as potential anti-Alzheimer agents.","authors":"Ahmad Mohammadi-Farani, Farzaneh Moradi, Amin Hosseini, Alireza Aliabadi","doi":"10.4103/RPS.RPS_257_23","DOIUrl":"10.4103/RPS.RPS_257_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Alzheimer's disease is the most common form of dementia and the sixth most common cause of death in the US according to the Alzheimer's Association. As regards, to date, no effective treatments are available because of the multifactorial nature of the disease, therefore, a large body of recent research has been allocated to the design and development of multi-target-directed ligands that can become effective drug candidates.</p><p><strong>Experimental approach: </strong>A novel series of benzamide derivatives (5a-5l) containing piperidine core were synthesized in the current work. After identification of the chemical structures of the members of this series using 1H NMR, IR, and MS spectra, their anti-acetylcholinesterase activity was assessed by the Ellman᾽s test. Docking studies were also performed to investigate the binding mode and determine the interacting amino acids with the corresponding ligands. Finally, the pharmacokinetic (ADME parameters) of the most potent derivative (5d) was predicted and compared with donepezil.</p><p><strong>Findings/results: </strong>Compound 5d possessing the fluorine atom substitution at position ortho was the most active compound in these series (IC₅₀ = 13 ± 2.1 nM). This compound demonstrated superior activity than the reference drug donepezil (IC₅₀ = 0.6 ± 0.05 µM). Molecular docking showed a significant hydrogen bonding of the carbonyl group of compounds 5d with tyrosine 121 into the active site of acetylcholinesterase. Fortunately, this compound showed better promising ADME properties than donepezil.</p><p><strong>Conclusion and implication: </strong>The benzamide derivatives introduced in this paper could be proposed as potential anti-acetylcholinesterase.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"698-711"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256631","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}

{"title":"Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model.","authors":"Ermi Girsang, Chrismis N Ginting, I Nyoman Ehrich Lister, Wahyu Widowati, Afif Yati, Hanna Sari Widya Kusuma, Rizal Azis","doi":"10.4103/RPS.RPS_177_22","DOIUrl":"10.4103/RPS.RPS_177_22","url":null,"abstract":"<p><strong>Background and purpose: </strong>Chlorogenic acid (CA) is a natural chemical that promises antiaging activity against photoaging skin damage. This research examined CA activities in mitigating skin photoaging.</p><p><strong>Experimental approach: </strong>UV-exposed human skin fibroblast cells were subjected to CA at 6.25, 12.5, and 25 μg/mL. The protein levels of cell secretion, such as cyclooxygenase (COX)-2, nitric oxide (NO), and interleukin (IL)-6 were measured using ELISA and colorimetry methods. Meanwhile, the mRNA expressions of glutathione peroxidase (GPX)-1, tissue inhibitor metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-1, caspase (CASP)-3, CASP-8, and fibroblast growth factor (FGF)-2 were quantified using the qRT-PCR method.</p><p><strong>Findings/results: </strong>CA treatment reduced inflammatory and aging biomarkers. CA at 6.25 μg/mL lowered NO, COX-2, and IL-6 levels to 89.44 μmol/L, 8.10 ng/mL, and 62.75 pg/mL, respectively. CA at 25 μg/mL resulted in the most significant down-regulation of MMP-1, CASP-3, and CASP-8 genes' expression (3.27, 1.25, and 3.59, respectively). Furthermore, treatment with CA at 25 µg/mL demonstrated the most notable activity in up-regulating antioxidant markers, specifically GPX-1, and extracellular matrix (ECM) integrity markers, including TIMP-1 and FGF-2 genes' expression.</p><p><strong>Conclusion and implications: </strong>CA imposes its anti-aging activity by decreasing inflammatory and aging biomarkers, and increasing cellular antioxidant and ECM integrity.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"746-753"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256601","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}

{"title":"Enhancement effect of urea toward electroporation-mediated plasmid transfection efficiency in the HEK-293 cell line.","authors":"Mahshid Mowla, Gilar Gorji-Bahri, Hamid Reza Moghimi, Atieh Hashemi","doi":"10.4103/RPS.RPS_185_23","DOIUrl":"10.4103/RPS.RPS_185_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Intracellular delivery is crucial in biological and medical studies. Although many molecular tools have been created for cell-based gene therapies, it remains challenging to introduce external molecules into cells. As one of the most popular non-viral transfection methods, electroporation induces transient pores in the cell membrane by applying an external electric field. Unsatisfactory transfection efficiency and low cell viability are the major drawbacks of electroporation. To overcome these issues, the current study investigated the effect of urea on electroporation-mediated transfection efficiency.</p><p><strong>Experimental approach: </strong>Three voltages of electroporation, including 100, 120, and 140 V, and 3 concentrations of urea buffer, including 0.25%, 0.5%, and 1% W/V, were considered as variables in this study. The HEK-293 cell line was used for transfection, and green fluorescent protein (GFP) expression was evaluated using flow cytometry and fluorescence microscopy.</p><p><strong>Findings/results: </strong>The results showed that the combination of electroporation and urea increased electroporation efficacy, but the effect depended on voltage and urea concentration. When different concentrations of urea were added to HEK-293 cells at a voltage of 100 V, the number of cells transfected by pEGFP-N1 increased (from 12.3 ± 0.2% in untreated cells to 17.35 ± 0.55%, 23.3 ± 0.3%, and 14 ± 0.1% at urea concentrations of 0.25%, 0.5%, and 1% W/V, respectively). The electroporation buffer containing 0.5% W/V urea showed the highest EGFP expression (23.3 ± 0.3%) and high cell viability (over 90%).</p><p><strong>Conclusion and implications: </strong>This research offers a new perspective for improving gene transfection efficiency once electroporation is utilized.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"766-773"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256605","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}

{"title":"Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin analogs on ErbB4 tyrosine phosphorylation.","authors":"La Ode Aman, Netty Ino Ischak, Teti Sutriyati Tuloli, Arfan Arfan, Aiyi Asnawi","doi":"10.4103/RPS.RPS_191_23","DOIUrl":"10.4103/RPS.RPS_191_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Lapatinib (FMM) and 5-fluorouracil (5-FU) are anticancer drugs employed in a combination approach. FMM inhibits tyrosine phosphorylation of ErbB4 while 5-FU inhibits cell proliferation. This research aimed to investigate the potential of two compounds, namely (1E,4E)-1,5-bis (4-hydroxyphenyl) penta-1,4-dien-3-one (AC01) and (1E,4E)-1,5-bis (3,4-dihydroxy phenyl) penta-1,4-dien-3-one (AC02), both as individual inhibitors and combination partners with FMM, targeting ErbB4 inhibition. AC01 and AC02 were combined with FMM, which targets ErbB4. The combination of 5-FU with FMM served as a reference in this study.</p><p><strong>Experimental approach: </strong>The research utilized computational simulation methods such as single and multiple ligands simultaneously docking and dynamics. Data analysis was performed using AutoDockTools and gmx_MMPBSA.</p><p><strong>Findings/results: </strong>Single docking results indicated that 5-FU exhibited the lowest binding affinity, while FMM demonstrated the highest. Simultaneous docking of AC01 and AC02 paired with FMM revealed their binding positions overlapping with the FMM-5-FU workspace. The FMM-AC01 and FMM-AC02 complexes exhibited slightly weaker binding affinities compared to FMM-5-FU. In combination with FMM, AC01 and AC02 occupied the ErbB4 activation loop, whereas 5-FU was outside the activation loop. Furthermore, in their interaction with ErbB4, AC02 exhibited slightly stronger binding than AC01, as confirmed by the average binding free energy calculations from molecular dynamics simulations.</p><p><strong>Conclusion and implications: </strong>In conclusion, computational simulations indicated that both AC01 and AC02 have the potential to act as anticancer candidates, demonstrating ErbB4 inhibitory potential both as individual agents and in synergy with FMM.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"754-765"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256628","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}

{"title":"Phytochemicals from <i>Pyrrosia longifolia</i> (Burm. f.) C.V. Morton with antibacterial activity.","authors":"Hilwan Yuda Teruna, Rohimatul Khodijah, Neni Frimayanti, Rudi Hendra","doi":"10.4103/RPS.RPS_151_23","DOIUrl":"10.4103/RPS.RPS_151_23","url":null,"abstract":"<p><strong>Background and purpose: </strong><i>Pyrrosia longifolia</i> is one of the medicinal plants in Indonesia. However, it has received little attention regarding pharmacological properties and phytochemicals. This study aimed to isolate bioactive compounds and evaluate their antibacterial activities.</p><p><strong>Experimental approach: </strong>The secondary metabolites were isolated using a bioassay-guided approach. The aerial part was macerated in methanol and the crude methanol was partitioned with organic solvents to obtain n-hexane, dichloromethane, ethyl acetate, and water extracts. The ethyl acetate extract was purified using chromatography procedures, yielding six chemicals, and their structures were determined using spectroscopy. The antibacterial activity of the compounds was evaluated.</p><p><strong>Findings/results: </strong>Six secondary phytochemical metabolites were identified including naringin (1), catechin (2), quercetin (3), rutin (4), kaempferol (5), and mangiferin (6). The absolute configurations of compounds 1 and 2 were ascertained using electronic circular dichroism as 2S for naringin and 2R, 3S for catechin. The compounds exhibited antibacterial activity against several pathogenic bacteria, with MIC and MBC values ranging from 7.8 to 250 μg/mL. Computational investigations of these compounds revealed a substantial affinity for bacterial receptors' active and allosteric regions. Furthermore, rutin exhibited the capacity to reduce the activity of β-ketoacyl-acyl carrier protein synthase III, enhancing its antibacterial effectiveness.</p><p><strong>Conclusion and implications: </strong>The <i>in-vitro</i> assessment revealed that the six identified compounds possess a wide range of antibacterial activity, which was corroborated by <i>in-silico</i> analyses. However, further investigation is required to back up the conclusion of this study.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"712-728"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256630","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}

{"title":"Ultra-small phospholipid nanoparticles in the treatment of combined hyperlipidemia: a randomized placebo-controlled clinical trial.","authors":"Alexander Archakov, Valery Kukharchuk, Andrey Lisitsa, Elena Ponomarenko, Yulia Romashova, Tatiana Pleshakova, Elena Yarovaya, Vladimir Kutsenko, Maria Guseva, Valery Beregovykh, Olga Ipatova, Marina Zubareva, Elena Tikhonova, Sergei Ivanov, Farid Bedretdinov, Sergey Markin","doi":"10.4103/RPS.RPS_274_23","DOIUrl":"10.4103/RPS.RPS_274_23","url":null,"abstract":"<p><strong>Background and purpose: </strong>Combined hyperlipidemia is associated with an increased risk of cardiovascular events. This clinical trial investigated phospholipovit (essential phospholipids, Institute of Biomedical Chemistry, Moscow, Russia), an ultra-small phospholipid nanoparticle (micelles), targeted to phospholipids of HDL in lowering non-HDL-cholesterol (non-HDL-C) and triglycerides (TG) levels in patients with combined hyperlipidemia and moderate cardiovascular risk.</p><p><strong>Experimental approach: </strong>A randomized, double-blinded, placebo-controlled phase II trial was conducted on 100 patients. Phospholipovit or placebo was randomly administered orally (500 mg) 2 times a day for 12 weeks. The primary endpoint was the percent change of non-HDL-C from baseline to 12 weeks of exposure.</p><p><strong>Findings/results: </strong>Treatment with phospholipovit resulted in a mean non-HDL-C reduction of 13.2% versus 4.3% compared with placebo. The absolute decrease in non-HDL-C was -23.2 (-48.7 - 7.0) mg/dL versus -7.3 (-17.0 - 12.0) mg/dL, significantly. The therapeutic target of non-HDL-C less than 130 mg/dL (3.4 mmol) was achieved in 15 of 39 patients (38.5%) in the phospholipovit group versus 2 of 41 patients (4.9%) in the placebo group OR 11.8 (2.4 - 116). Significant reduction in TG, apolipoprotein B, total cholesterol, and very low-density lipoprotein cholesterol levels was also observed. There were no changes in the liver and kidney functions, vital signs, or electrocardiography. There were no serious adverse events.</p><p><strong>Conclusion and implications: </strong>Phospholipovit significantly reduced non-HDL-C, TG, and atherogenic lipoproteins in patients with combined hyperlipidemia and moderate cardiovascular risk. It can be used as an add-on therapy to statins.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"656-668"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256564","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}

{"title":"Exploring the inhibitory potential of xanthohumol on MEK1/2: a molecular docking and dynamics simulation investigation.","authors":"Zohreh Gholizadeh Siahmazgi, Shiva Irani, Ali Ghiaseddin, Fereshteh Soutodeh, Zahra Gohari, Jaber Afifeh, Amirreza Pashapouryeganeh, Hilda Samimi, Mahmood Naderi, Parviz Fallah, Vahid Haghpanah","doi":"10.4103/RPS.RPS_38_24","DOIUrl":"10.4103/RPS.RPS_38_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Xanthohumol (Xn), a small molecule found in <i>Humulus lupulus</i>, has shown promise as an anti-cancer compound. This in silico study was performed to understand the mechanism of action of Xn as a natural compound on MEK1/2 by simulation.</p><p><strong>Experimental approach: </strong>After ligand and protein preparation, the best binding energy was determined using Autodock 4.2. Additionally, molecular dynamics simulations of the MEK1/2-Xn and BRaf-MEK1/2-Xn complexes were conducted using GROMACS 2022.1 software and compared to the complexes of MEK1/2-trametinib (Tra) and BRaf-MEK1/2-Tra.</p><p><strong>Findings/results: </strong>The docking results revealed that the best binding energies for MEK1-Xn (-10.70 Kcal/mol), MEK2-Xn (-9.41 Kcal/mol), BRaf-MEK1-Xn (-10.91 Kcal/mol), and BRaf-MEK2-Xn (-8.54 Kcal/mol) were very close to those of the Tra complexes with their targets, MEK1 and MEK2. Furthermore, Xn was found to interact with serine 222 at the active site of these two kinases. The results of the molecular dynamics simulations also indicated that Xn induced changes in the secondary structure of the studied proteins. The root mean square of proteins and the mean radius of gyration showed significant fluctuations.</p><p><strong>Conclusion and implications: </strong>The findings of the study suggested that Xn, as a novel bioactive compound, potentially inhibits the MEK1/2 function in cancer cells.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"669-682"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256611","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}

{"title":"Immunoinformatic approach to the design of a novel multi-epitope vaccine against <i>Leishmania major</i> fused to human IgG-Fc.","authors":"Mahmood Fadaie, Zabihollah Shahmoradi, Hossein Khanahmad","doi":"10.4103/RPS.RPS_145_24","DOIUrl":"10.4103/RPS.RPS_145_24","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these <i>Leishmania major</i> proteins.</p><p><strong>Experimental approach: </strong>The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses.</p><p><strong>Findings/results: </strong>The results demonstrated the vaccine's antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes.</p><p><strong>Conclusion and implications: </strong>These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"729-745"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256618","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}

{"title":"MicroRNA-219 in the central nervous system: a potential theranostic approach.","authors":"Nahal Shamaeizadeh, Mina Mirian","doi":"10.4103/RPS.RPS_163_23","DOIUrl":"10.4103/RPS.RPS_163_23","url":null,"abstract":"<p><p>Despite the recent therapeutic advances in neurological disorders, curative therapy remains a serious challenge in many cases. Even though recent years have witnessed the development of gene therapy from among the different therapeutic approaches affecting pathophysiological mechanisms, intriguing aspects exist regarding the effectiveness, safety, and mechanism of action of gene therapies. Micro ribonucleic acid (microRNA-miRNA), as a fundamental gene regulator, regulates messenger ribonucleic acid (mRNA) by directly binding through the 3'-untranslated region (3'-UTR). MicroRNA-219 is a specific brain-enriched miRNA associated with neurodevelopmental disorders that play crucial roles in the differentiation of oligodendrocyte progenitorcells, promotion of oligodendrocyte maturation, remyelination, and cognitive functions to the extent that it can be considered a potential therapeutic option for demyelination in multiple sclerosis and spinal cord injury and reverse chronic inflammation pains. Additionally, miR-219 regulates the circadian clock, influencing the duration of the circadian clock period. This regulation can impact mood stability and is associated with phase fluctuations in bipolar patients. Furthermore, miR-219 also plays a role in modulating tau toxicity, which is relevant to the pathophysiology of Alzheimer's disease and schizophrenia. Finally, it reportedly has protective effects against seizures and Parkinson's disease, as well as neoplasms, by inhibiting proliferation, suppressing invasion, and inducing cell death in tumor cells. Exploring the miR-219 molecular pathways and their therapeutic effects on central nervous system disorders and the mechanisms involved, the present review study aims to illustrate how this information may change the future of gene therapy.</p>","PeriodicalId":21075,"journal":{"name":"Research in Pharmaceutical Sciences","volume":"19 6","pages":"634-655"},"PeriodicalIF":2.1,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256627","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}