Background: Lung cancer remains a major global health burden, and conventional therapies often fail to meet clinical needs. Although non-coding RNAs are increasingly recognized as key regulators in cancer, the role of NKILA and its modulation by the miR-103/107 cluster in lung cancer growth and metastasis is not fully characterized. This study investigates the impact of the NKILA–miR-103/107 axis on lung cancer progression and metastatic behavior. Methods: To suppress miR-103 and miR-107 activity in the human lung cancer cell line A549, specific LNA-based inhibitors were introduced into the cells. Following in vitro transfection with either miR-specific LNA or a mock control, alterations in the components of the NKILA–miR-103/107 regulatory pathway were quantified using quantitative real-time PCR. The effects of miR inhibition on cellular behavior were then evaluated by measuring A549 cell growth with an MTT assay and assessing invasive capacity through a Transwell invasion test. Results: In lung cancer A549 cells, suppression of miR-103/107 using LNA inhibitors led to a marked elevation in NKILA transcript levels. Functional assays showed that miR-103/107 inhibition was associated with a significant decrease in A549 cell viability (p=0.0041) and a pronounced reduction in invasive capacity (p=0.001). Conclusion: In this in vitro study using A549 lung cancer cells, the NKILA–miR-103/107 axis was associated with lung cancer aggressiveness. miR-103/107 inhibition upregulated NKILA and was accompanied by decreased proliferation and invasion of A549 cells. These findings are preliminary and limited to a single cell line model. Further validation in additional lung cancer models and in vivo systems is required to determine the broader biological and therapeutic relevance of this regulatory interaction.
Osteoarthritis (OA) is a common degenerative joint disease characterized by pain, stiffness, progressive cartilage loss, and reduced mobility. Current treatments primarily aim to relieve symptoms rather than restore damaged cartilage, and durable regeneration of native hyaline cartilage remains a major clinical challenge. Extracellular Vesicles (EVs), particularly those derived from Mesenchymal Stem Cells (MSCs), have emerged as promising cell-free therapeutic platforms because of their ability to modulate inflammation, regulate chondrocyte activity, and influence extracellular matrix metabolism. However, EV heterogeneity, source-dependent variability, limited targeting efficiency, inconsistent cargo loading, and lack of standardized manufacturing protocols continue to restrict their clinical translation. This review summarizes recent advances in engineered EV-based strategies for OA and cartilage repair, including parental-cell preconditioning, genetic modification, surface functionalization, cargo loading, artificial EV platforms, and biomaterial-assisted delivery. Importantly, we distinguish between in vitro findings, preclinical animal studies, and early clinical evidence to provide a balanced assessment of translational readiness. We also discuss key regulatory and safety challenges, including GMP-compliant production, batch-to-batch variability, quality-control criteria, potency assays, scalability, biodistribution, and long-term safety. By integrating EV engineering with translational and regulatory perspectives, this review highlights the potential of engineered EVs as future disease-modifying tools for OA while emphasizing that their clinical efficacy and capacity to restore durable hyaline cartilage remain to be demonstrated in robust human studies.
Background:Inhibition of angiogenesis is an attractive approach in cancer therapy. Both curcumin and silver nanoparticles (AgNPs) have demonstrated anti-angiogenic properties; however, the the poor water solubility of Curcumin and the side effects of AgNPs adversely affect their activity. Methods:In this study, AgNPs coated with curcumin (Cur-AgNPs), was used to improve aqueous-phase solubility of curcumin and decrease the side effects of AgNPs. Afterwards, treatment with curcumin enhanced the anti-angiogenic activity of Cur-AgNPs. The nanoparticles were synthesized as both reducing and stabilizing agents. Evaluation of anti-angiogenesis was assessed in vitro using Human Umbilical Vein Endothelial Cells (HUVECs) and in vivo through the Chorioallantoic Membrane (CAM) assay. Data were analyzed by one-way ANOVA with Tukey's multiple comparison test. Results:Synthesized Cur-AgNPs have an average diameter of 39 nm, with spherical shapes and an absorbance peak at 450 nm in the UV-visible spectrum. Cur-AgNPs showed a negative zeta potential. EDAX and FTIR confirmed the conjugation of curcumin with AgNPs. In vitro anti-angiogenesis assays demonstrated that Cur-AgNPs reduced the viability of HUVECs, an Inhibitory Concentration (IC50) value of 13 μg/ml. DAPI and acridine orange/propidium iodide staining revealed a significant increase in apoptotic cells following treatment with Cur-AgNPs. The expression of Matrix Metalloproteinase 9 (MMP-9) and Cyclooxygenase-2 (COX-2) was also inhibited in treated cells. In vivo anti-angiogenesis assays using the CAM model showed significant decrease in the number, length and hemoglobin content of CAM blood vessels. Conclusion:Curcumin conjugated with AgNPs may represent a promising strategy to enhance the therapeutic potential of both AgNPs and curcumin. However, further investigations, particularly regarding safety and biocompatibility of Cur-AgNPs, is needed in this field.
Background: Breast cancer is the most widespread malignancy among women worldwide. Luteolin, a flavonoid, has demonstrated anti-cancer effects by triggering apoptosis in tumor cells. Exosomes are gaining much attention for cancer therapeutic approaches due to multitude of beneficial effects. This study is aimed to investigate the possible potential of exosomes derived from luteolin-treated 4T1 cells to ameliorate tumor in comparison to luteolin treatment only. Methods: In this study, 4T1 cell culture was exposed to luteolin. Following exosome extraction, they were characterized using field emission scanning electron microscopy, dynamic light scattering and western blot analysis. MTT assay was performed in order to evaluate cell viability after exposure to different concentrations of luteolin and exosomes. An in vivo breast cancer model was induced via subcutaneous injection of 4T1 cells to the BALB/C mice. After 14 days, tumor volume was measured, and expression of RhoA and ERK mRNAs were quantified by Real Time PCR. Results: The MTT assay demonstrated that exosomes from luteolin-treated 4T1 cells at a concentration of 320 μg/μl reduced cell viability by approximately 70% in a dose-dependent manner. Tumor volume in the exosome-treated group decreased by 57% relative to the tumor group, while the luteolin-treated group demonstrated a 39% reduction. Furthermore, RhoA gene expression was substantially downregulated in the exosome-treated group, and exosomes were more effective than luteolin in reducing ERK gene expression. Conclusion: Exosomes derived from luteolin-treated 4T1 cells effectively suppress breast cancer cell growth by reducing 4T1 cell viability and by decreasing tumor volume and downregulating tumor-associated genes RhoA and ERK. These results propose a novel therapeutic strategy for breast cancer, highlighting the promising potential of exosomes as an efficient drug delivery system.
Background: This project aimed to evaluate the anti-melanogenic characteristics of Nasturtium officinale (N. officinale) by assessing the impact of both aqueous and hydroalcoholic extracts on the inhibition of cellular and mushroom tyrosinase enzymes, as well as the suppression of the melanin synthesis in B16F10 melanoma cells. Methods: The aerial components of N. officinale were subjected to extraction using distilled water: ethanol (7:3) through the maceration technique. The extract’s phenolic compounds were quantified employing the Folin-Ciocalteu method. The evaluation of the safety profile of the extracts on B16F10 cells was done by the MTT assay. Subsequently, the melanin concentration in B16F10 cells, alongside the inhibitory effects on both mushroom and cellular tyrosinase, was assessed following treatment with the aforementioned extracts. Results: The aqueous and hydroalcoholic extracts exhibited no significant toxicity on B16F10 when compared to Phosphate-Buffered Saline (PBS). Additionally, there was no notable difference in the cytotoxic effects of extracts on the B16F10 cell line. Both extracts resulted in inhibition of cellular and mushroom tyrosinase, along with a decrease in melanin levels in B16F10 in a concentration-dependent manner. Ultimately, the total phenolic content in the aqueous and hydroalcoholic extracts was found to be approximately 14 and 30 mg/g of gallic acid, respectively. Conclusion: This in vitro investigation offers evidence supporting the skin brightening properties of N. officinale as an anti-melanogenic agent. Given its safety profile and absence of toxic effects on melanoma cells, it may be incorporated into the formulation of skin-brightening products following preclinical tests.
Background: Mesenchymal Stem Cells (MSCs) play a pivotal role in regenerative medicine due to their multipotency and immunomodulatory properties. However, during in vitro expansion, MSCs undergo senescence, characterized by a decline in proliferation, impairment of differentiation potential, and altered secretory profiles, which limits their therapeutic efficacy. This study aimed to identify novel molecular regulators and network-level interactions underlying MSC senescence through microarray analysis of the GSE7888 dataset, comparing early and senescent MSCs. Methods: A total of 4597 Differentially Expressed Genes (DEGs) were identified between early (passages 4-5) and senescent (passages 22-28) MSCs, with 2219 upregulated and 2379 downregulated. Key regulators such as CDKN1A (p21), CDK4, and CDK6 were implicated in cell cycle arrest and the progression of senescence. Pathway analysis highlighted the mTOR, FoxO, and p53 signaling pathways as key regulators of stress responses, metabolism, and aging. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted cellular processes, including protein transport and intracellular signaling, while protein-protein interaction networks identified high-connectivity nodes such as TP53, FOXO3, and MDM2. Senescent MSCs displayed phenotypic changes, including altered morphology and the emergence of the Senescence-Associated Secretory Phenotype (SASP), which impaired regenerative potential. Results: The findings suggest that targeting the mTOR, FoxO, and p53 pathways could delay senescence and enhance MSC therapeutic potential. Interventions such as rapamycin and FoxO3 activators show promise in reversing senescence. Conclusion: Future research should explore small molecules and gene-based therapies targeting senescence pathways to improve MSC-based regenerative strategies. These results provide a foundation for developing innovative approaches to optimize MSC applications in clinical therapies
Background: Mycobacterium simiae (M. simiae) is a non-tuberculous mycobacterium (NTM) that closely resembles Mycobacterium tuberculosis (M. tuberculosis) in clinical and biochemical characteristics, notably its niacin-positive phenotype. This similarity frequently leads to misdiagnosis and inappropriate treatment with first-line anti-tuberculosis drugs, to which M. simiae is frequently resistant. Current diagnostic methods are expensive or need complex equipment, highlighting the urgent need for a rapid, specific, and accessible molecular target to identify M. simiae accurately. Methods: In this study, a modified genome comparison method was applied to the complete reference genome of M. simiae (AP022568.1) in order to identify a putative species-specific nucleotide sequence. A conventional PCR assay was designed to amplify a 168-bp fragment within this target, designated MST601 (M. simiae Target, 601 bp). The analytical sensitivity [Limit of Detection (LOD)] was determined using serial dilutions of genomic DNA. The pilot evaluation of the assay was assessed using 10 well-characterized clinical isolates of M. simiae. Results: The MST601-PCR assay demonstrated high analytical sensitivity, with a limit of detection of ~10 fg (≈2 genome equivalents per reaction) of M. simiae genomic DNA. No cross-reactivity among the tested species was observed with any of the 10 non-target mycobacterial species tested. The assay successfully amplified the target sequence from all 10 clinical isolates. Sequencing of the amplicons revealed ≥99% identity to reference M. simiae strains in the GenBank database, validating the assay's accuracy. Conclusion: A species-specific nucleic acid target, MST601, facilitating the rapid and accurate detection of M. simiae via conventional PCR was presented. This assay provides a low-cost and accessible option for diagnostic laboratories.
Background:In recent years, the number of adults aged 20-79 years living with diabetes has increased more than threefold. Currently, the treatment of diabetes typically involves the long-term use of chemical and herbal drugs. However, prolonged use of chemical drugs may lead to side effects that can be detrimental to health. Therefore, this study aims to normalize blood glucose levels and restore kidney and heart cells. Methods:The research was conducted using diabetic mice as experimental subjects. The treatment involved exposure to an alternating Magnetic Field with Magnetic Flux Densities of 0.3 and 0.6 mT for 20 min/day over five consecutive days. The frequencies of the applied Magnetic Fields were 50, 100, 150, and 200 Hz. Results:The results showed that the greatest reduction in blood glucose levels (92.11%) was observed at a frequency of 100 Hz and an Magnetic Flux Density of 0.6 mT. Meanwhile, the highest increase in hemoglobin levels (81.11%) occurred at a frequency of 150 Hz and a Magnetic Flux Density of 0.3 mT. Other parameters that experienced non-linear changes included cholesterol levels, blood viscosity, and erythrocytes count, glomerulus and kidney cell density, and heart cell density. Conclusion:The optimal effects of magnetic field exposure do not always occur at the same frequency or Magnetic Flux Density.
Background:Inflammatory Bowel Disease (IBD) is a complex disorder for which the mechanisms and targeted therapies remain unclear. Several in vitro models, including organoids, cytokine-stimulated Caco-2 monolayers, and co-culture systems, have been developed to study IBD pathogenesis and potential treatments. Meanwhile, the Caco-2/THP-1 co-culture is a practical model representing the interaction of intestinal epithelial and immune cells. However, multiple factors, such as culture duration and exposure time to inflammatory agents, significantly affect model outcomes. Developing an optimized co-culture that better mimics intestinal inflammation can introduce a valuable method for future studies. This study aimed to optimize a Caco-2/THP-1 co-culture model, focusing on culture timing and treatment conditions. Methods:THP-1 monocytes were differentiated into macrophage-like cells (M0) with phorbol 12-myristate 13-acetate (PMA, 50 ng/ml, 48 hr). M0 cells were treated with different Lipopolysaccharide (LPS) concentrations for 6 or 24 hr to determine the optimal inflammatory dose. Inflammatory macrophages (M1) were co-cultured with differentiated or undifferentiated Caco-2 monolayers. Expression of IL-6, IL-8, and TNF-α was measured by qRT-PCR, M1 macrophage markers (CD86/HLA-DR) by flow cytometry, and nitric oxide by the Griess assay. Results:Stimulation with 100 ng/ml LPS for 6 hr increased M1 (CD86+/HLA-DR+) macrophages to 58.9% and induced maximal nitric oxide production (179.3 μM). Co-culture with these M1 cells enhanced IL-8 and modestly increased IL-6 expression in differentiated Caco-2 cells compared with other groups. Conclusion:The differentiated Caco-2/THP-1 co-culture efficiently mimics intestinal inflammation observed in IBD and provides an optimized in vitro model for further investigations.
Background: Gastric Cancer (GC) poses a substantial global health threat, ranking as the second leading cause of cancer-related mortality among gastrointestinal malignancies. This investigation explores the potential therapeutic implications of plant extracts on gastric cancer, with a specific focus on their effects on the innate immune system. Methods: A comprehensive analysis was conducted using 200 Sequence Read Runs (SRRs) thigh samples associated with gastrointestinal cancer tissue, juxtaposed with pathologically confirmed healthy tissues serving as controls. Differential Gene Expression (DGE) testing, encompassing the examination of 28,000 genes, including 95 pivotal genes associated with the innate immune system, was conducted. Findings elucidate alterations in the expression of key pattern recognition receptors, such as TLR2 and TLR4, as well as pivotal molecules within their signaling pathways. In pursuit of potential antagonists for these receptors, virtual screening on the Maestro docking platform in the Schrödinger 2022 package was conducted, evaluating 220,000 diverse tautomer’s of plant active substances. Selected candidates, exhibiting superior docking scores across four additional platforms, were subjected to further scrutiny. Results: MMT results showed that nettle extract showed significant cytotoxic effects within 12 hr compared to the control (no treatment) sample, resulting in a 34.7% reduction in AGS cancer cell viability. The flow cytometry test showed that the control group had 71%, and groups treated with nettle extract for two and 12 hr had 65.3 and 67.18% viable cells, respectively. These differences were not statistically significant, indicating that nettle extract selectively preserves healthy living cells. Conclusion: Cytotoxicity tests and cell cycle assessments confirmed the ability of nettle extract to reduce the survival of GC cells. This property makes nettle a promising candidate for drug development in this direction.
Recent advances in Artificial Intelligence (AI) have profoundly transformed the field of genome editing, particularly through integration with the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology. This review highlights how AI-driven computational models are reshaping guide RNA (gRNA) design, off-target prediction, and editing precision in CRISPR–Cas systems. A PRISMA-informed literature survey was conducted using PubMed, Scopus, EMBASE, and Google Scholar databases to identify studies exploring AI-assisted CRISPR applications in gene therapy and biomedical research. The results demonstrate that deep learning, machine learning, and reinforcement learning approaches significantly enhance prediction accuracy, algorithmic efficiency, and translational potential across genetic diseases such as β-thalassemia, muscular dystrophy, and cancer. Moreover, ethical challenges, algorithmic bias, and data security concerns remain critical barriers to clinical adoption. This review also discusses the emerging landscape of AI-assisted CRISPR research in Iran, emphasizing national progress, infrastructural constraints, and future opportunities. Overall, the convergence of AI and CRISPR technologies promises to advance precision medicine by accelerating the development of personalized, efficient, and ethically responsible genome-editing solutions.
Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have emerged as a pivotal tool in nanomedicine, offering potential in drug delivery, imaging, and targeted therapies. However, their application is challenged by issues such as cytotoxicity, uneven biodistribution, and biocompatibility. SPIONs are predominantly cleared through renal or hepatobiliary pathways, with size and charge playing critical roles in determining their fate. While smaller SPIONs optimize renal clearance, their propensity to agglomerate and activate macrophages may induce inflammatory responses. Radiolabeled SPIONs face additional challenges in molecular imaging and nuclear medicine. Emerging strategies, such as chelator-free radiolabeling and multi-component nanoparticles, aim to address these limitations by improving targeting specificity and enhancing biocompatibility. Looking forward, SPIONs hold immense potential in theranostics, particularly in integrating imaging with targeted drug delivery and therapies. Advances in synthesis and surface functionalization may enhance their safety and effectiveness. Future research should focus on optimizing SPIONs, integrating them with therapeutic agents, and improving targeting and clearance mechanisms. Collaboration among experts and the use of Artificial Intelligence (AI) modeling could accelerate their development for personalized treatment applications. This review uniquely highlights recent advances in radiolabeled SPIONs for molecular imaging and targeted therapy, addressing challenges like biocompatibility, stability, and translational applicability.
Background: This study explores repetitive Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) sequences from the archaea Acidianus sp. and Acidianus ambivalens (A. ambivalens), as well as from the bacterium Yersinia ruckeri (Y. ruckeri). These sequences are compared with human microRNA (miRNA) sequences to investigate potential genetic similarities and disease associations. Methods: CRISPR sequences were retrieved from the CRISPR/Cas++ database, and human miRNA sequences were obtained from miRBase. Sequence alignments were performed using BLASTn with an E-value threshold of 1e-5 to identify significant similarities. Genes associated with matched human miRNAs were identified through the HGNC and GeneCards databases. Further analyses included comparison with disease-associated miRNAs reported in human and mouse datasets. Results: In Y. ruckeri, alignments revealed similarities to miRNAs linked with genes such as FOXO1, PTEN, PAX7, and DOCK3, which are associated with lung cancer and muscular dystrophies. In A. ambivalens, aligned miRNAs corresponded to loci including CHM13 and GRCh38, potentially linked to periembolic adenocarcinoma and mild pre-eclampsia. For Acidianus sp., matches were observed with miRNAs associated with genes like Irak2, NOS2, STAT1, and Numb, which have been implicated in Psoriatic arthritis, Alzheimer’s disease, Hepatocellular carcinoma, and Coronary artery di sease. Conclusion: CRISPR sequences from these prokaryotes show notable similarities with human miRNAs, suggesting possible indirect links to genes involved in major diseases. These preliminary findings emphasize the need for further investigation into shared sequence motifs and their functional roles in host-pathogen interactions or evolutionary biology.
Background: Teeth are vital structures prone to issues such as caries and plaque formation, often caused by Streptococcus mutans (S. mutans). This issue can be mitigated using natural ingredients like mangosteen fruit (Garcinia mangostana L.), especially its peel, is known for its medicinal benefits. However, its extract may take time to show effects, so it is being combined with nanosilver for improved drug distribution. To observe the antibacterial and antibiofilm potential of Mangosteen Peel Extract (MPE) in nanosilver form as a preventive agent in dentistry. Methods: The extraction was succeeded by a phytochemical assay and biosynthesis of MPE into Mangosteen Peel Extract Nanosilver (MPNs). Particle Size Analysis (PSA) and Transmission Electron Microscopy (TEM) were used to study this procedure. Disc diffusion tests were used to evaluate the antibacterial properties, and the Minimum Inhibition Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were also determined. Furthermore, the antibiofilm activity against S. mutans was investigated. Results: the phytochemical contents in MPE were flavonoids, tannins, saponins, phenols, alkaloids, triterpenoids, and terpenoids. Particle size of MPNs was 126.1 nm and the Polydispersity Index (PDI) was 0.419. The highest antibacterial concentration as inhibition zone against S. mutans was 16.37±0.38 mm and 119.37±2.16% inhibitory activity, at the highest concentration (100%) p<0.05. The percentage of biofilm inhibition against S. mutans was 27.64-105.94% which was concentration dependent. Conclusion: MPNs has potential as an antibacterial and antibiofilm agent that can be used as a preventive agent in medicine.
This study investigates the synergy between Traditional Persian Medicine (TPM)'s concept of innate heat (Hararat-e-Gharizi) and modern mitochondrial thermoregulation. TPM emphasizes innate heat as essential for sustaining life, paralleling modern understandings of mitochondrial ATP production and heat generation. This integration occurs through mitochondrial biogenesis, proton leak (via uncoupling proteins), and Reactive Oxygen Species (ROS) signaling, which correspond to the TPM concept of heat sustaining vital functions. These findings may guide novel therapeutic strategies that integrate TPM principles with mitochondrial biology. A comprehensive review of historical TPM texts and modern literature was conducted, comparing innate heat with mitochondrial roles in thermoregulation and energy balance. Data from PubMed, Google Scholar, and Scopus were analyzed to explore mechanisms of heat production in both traditional and modern contexts. Findings demonstrated that TPM's innate heat correlates with mitochondrial biogenesis, heat generation via Uncoupling Proteins (UCP1), and ROS regulation. These concepts reflect TPM’s understanding of maintaining bodily warmth for health and longevity. The relationship between Hararat-e-Gharizi and mitochondrial thermogenesis offers a bridge between ancient medicinal practices and modern cellular biology. Both emphasize the role of heat in maintaining homeostasis and preventing disease, with modern science validating TPM's holistic approach. Clarifying these mechanisms provides deeper insight into therapeutic implications, highlighting thermodynamic parallels and the role of ROS signaling as a novel framework for understanding disease etiology and treatment. This study bridges Traditional Persian Medicine and modern mitochondrial thermoregulation, introducing integrative perspectives for personalized healthcare. It also highlights thermodynamic parallels and ROS signaling as a novel framework for understanding disease etiology and treatment. This study underscores the relevance of TPM’s innate heat in modern medicine, emphasizing the importance of mitochondrial efficiency in thermoregulation and overall health. Integrating these perspectives can enhance personalized therapeutic strategies for disease prevention and longevity
Background:Foot-and-Mouth Disease (FMD) remains a persistent global threat to livestock health and food security, particularly in endemic and resource-constrained regions. Conventional inactivated vaccines pose several challenges-including biosafety risks and dependence on cold-chain logistics. These limitations have prompted growing interest in plant-based recombinant vaccine platforms as innovative, scalable, and safer alternatives for FMD prevention. Methods:This study employed a qualitative meta-synthesis approach, guided by the Barroso-Sandelowski method, to systematically extract, interpret, and integrate findings from 35 peer-reviewed empirical studies published between 2000 and 2025. The selected studies focused on the development and evaluation of plant-made vaccines targeting FMD. Thematic coding and interpretive synthesis were applied to identify recurrent patterns, challenges, and opportunities across the literature. Results:The analysis yielded four dominant themes: (1) Platform Diversity: A variety of plant and algal expression hosts were used through transient or stable transformation systems, (2) Immunization Routes: Oral vaccination was noted for its logistical advantages and potential for mass immunization, though often requiring adjuvants to enhance immunogenicity, (3) Scale-Up Challenges: Key barriers included low recombinant protein yields, heterogeneity in post-translational modifications and high variability between production batches and (4) Regulatory Readiness: Despite encouraging pre-clinical data, most candidates have not progressed beyond experimental stages. Conclusion:Plant-based recombinant vaccines represent a promising frontier in the fight against FMD, offering novel avenues for safer, more accessible immunization strategies. However, their transition from bench to field remains hindered by technical limitations in expression and purification, as well as institutional and regulatory gaps.
Background:Resistance to antimalarial medications, particularly in Plasmodium falciparum (P. falciparum), has emerged as a significant challenge, highlighting the need for innovative therapeutic strategies. Green-synthesized magnesium oxide nanoparticles (MgO NPs) represent a promising approach to therapeutic interventions. This study presents one of the first detailed evaluations of green-synthesized MgO NPs derived from Achillea millefolium (A. millefolium) against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) P. falciparum strains. Methods:In this study, MgO NPs were biosynthesized using A. millefolium extracts with varying solvent ratios. The nanoparticles were characterized using UV-Vis, FTIR, FESEM, and DLS techniques. Cytotoxicity was assessed via MTT and hemolysis assays. Their antiplasmodial efficacy was evaluated in vitro against chloroquine-sensitive (3D7) and -resistant (K1) P. falciparum strains. Results:The synthesized MgO NPs displayed quasi-spherical morphology and nanoscale size. Among tested formulations, the most effective showed IC50 values of 0.17 mg/ml for the 3D7 strain and 0.76 mg/ml for the K1 strain, indicating significant antiplasmodial activity. Conclusion:Green-synthesized MgO NPs using A. millefolium demonstrated potent antiplasmodial activity at low IC50 concentrations, showing efficacy against both chloroquine-sensitive and -resistant P. falciparum strains. These findings highlight their promise as plant-based nanotherapeutics for malaria treatment.
Background: Rheumatoid Arthritis (RA) is a chronic inflammatory joint disease. Current treatments often have limited efficacy and cause side effects due to their nonspecific action, while early diagnosis is challenging. This study combined bioinformatics and experimental methods to identify key genes and pathways involved in RA, aiming to discover novel therapeutic targets and diagnostic biomarkers. Methods: RNA-seq data from immune cells of RA patients and healthy donors (GSE117769) were analyzed with DESeq to identify Differentially Expressed Genes (DEGs). Affected pathways were explored using EnrichR, and druggable genes were identified through DGIdb and a literature review. Expression of candidate genes was validated in additional RA blood and synovium microarray datasets (GSE45291, GSE82107, GSE77298) using the GEO2R tool. Finally, RT-qPCR was used to measure the expression of selected genes in Peripheral blood Mononuclear Cells (PBMCs) from newly-diagnosed and chronic RA patients and controls, with associations to clinical features and diagnostic accuracy assessed. Synovial fluid of RA patients were stained with Giemsa. Results: Combined in-silico and experimental analysis demonstrated significant upregulation of CA1, OLAH, and ADAMTS2 in the PBMCs of RA patients. However, only ADAMTS2 showed high expression in the synovial tissue of these patients. While OLAH and ADAMTS2 were predominantly overexpressed in newly-diagnosed cases, CA1 levels were consistently elevated in both early and chronic stages of RA. Conclusion: This study identified CA1, OLAH, and ADAMTS2 as being upregulated in RA, with ADAMTS2 showing promise as a therapeutic target, suggesting it may also have potential as a candidate for diagnosis and treatment.
