Research in Molecular Medicine

en Nanocarriers: A New Paradigm for the Treatment of Cutaneous Leishmaniasis review review Cutaneous leishmaniasis (CL) remains a neglected tropical disease with significant psychosocial and economic impacts, primarily affecting resource-limited regions. Current chemotherapies, including pentavalent antimonials, amphotericin B, and miltefosine, are plagued by systemic toxicity, poor bioavailability, emerging drug resistance, and inadequate targeting of intracellular Leishmania amastigotes within macrophages. Nanomedicine has emerged as a new strategy to overcome these limitations by repurposing existing drugs through advanced delivery systems. This review comprehensively examined the application of various nanocarrier platforms, including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, and metallic nanoparticles for the treatment of CL. These systems function by leveraging passive targeting via the enhanced permeability and retention (EPR) effect at lesion sites and active targeting through innate macrophage phagocytosis. Key advantages include enhanced drug solubility, prolonged circulation, improved bioavailability, reduced systemic toxicity, and increased intracellular drug accumulation. The clinical success of liposomal amphotericin (AmBisome®) exemplifies the potential of nanomedicine, offering high efficacy with minimal nephrotoxicity. Topical applications of SLNs/NLCs show promise for non-invasive treatment, while polymeric and metallic nanoparticles enable controlled release and multimodal therapy. Despite these advancements, challenges related to scalability, regulatory approval, long-term stability, and affordability in endemic regions remain. Future directions include the development of ligand-functionalized “smart” nanoparticles, combination therapies, and plant-based nanoformulations. Nanomedicine represents a paradigm shift in CL treatment, bridging the gap between drug efficacy and clinical applicability through precision targeting and enhanced therapeutic outcomes. Cutaneous leishmaniasis, nanomedicine, drug delivery, targeted therapy 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1428-1&slc_lang=en&sid=1 Reza Ghasemikhah ghasemikhah@yahoo.com 100319475328460013680 100319475328460013680 No Department of Parasitology and Mycology, School of Medicine Arak University of Medical Sciences, Arak, Iran. Majidreza Adelani Dradelanimajidreza@gmail.com 100319475328460013681 100319475328460013681 No Department of Internal Ward, Pulmonary and Critical Care Division, Mazandaran University of Medical Sciences, Sari, Iran. Ali Ehsan Shahbazi Shahbazy1354@yahoo.com 100319475328460013682 100319475328460013682 No Department of Parasitology, Saveh University of Medical Sciences, Saveh, Iran. Eissa Soleymani soleymanieissa@gmail.com 100319475328460013683 100319475328460013683 No Toxoplasmosis Research Center, Communicable Diseases Institute, Mazandaran University of Medical. Seyedmousa Motavallihaghi mousamotevalli@gmail.com 100319475328460013684 100319475328460013684 Yes 6. Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

en Atypical Cutaneous Leishmaniasis with Negative Direct Smear: Two Case Reports Confirmed by Molecular Diagnosis Special Issue: “Leishmaniasis” Special Issue: “Leishmaniasis” گزارش مورد case report <div style="text-align: justify;">Background: Cutaneous leishmaniasis (CL) is a chronic parasitic disease caused by protozoa of the genus Leishmania, primarily transmitted to humans by bites of infected female sandflies. Case presentation: A 5-year-old girl from Damghan presented with a chronic lesion on her hand that was initially misdiagnosed as a fungal infection; however, a kDNA-based PCR assay confirmed CL despite negative direct smears. A 43-year-old man from the same region had a painful ulcerative leg lesion misdiagnosed as fungal; kDNA-based PCR confirmed Leishmania major infection, and he improved following treatment with glucantime. These cases illustrate the diagnostic challenges posed by atypical presentations and underscore the importance of molecular diagnostics for accurate detection in endemic areas. Conclusion: Atypical CL presents diverse clinical features, especially in children, which complicate diagnosis. Increased awareness and further research are crucial to improving outcomes and refining management strategies.</div> Atypical presentations, cutaneous leishmaniasis, Case report, Molecular test 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-183-2&slc_lang=en&sid=1 Hajar Ziaei Hezarjaribi ziaei2000@yahoo.com 100319475328460013693 100319475328460013693 No Toxoplasmosis Research Center, Communicable Diseases Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Mahdi Fakhar mahdifakhar53@gmail.com 100319475328460013694 100319475328460013694 Yes Gastroenterology and Hepatology Diseases Research Center, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran. Amir Mohammad Fallahi Lima amirlimaaa9@gmail.com 100319475328460013695 100319475328460013695 No Mazandaran University of Medical Sciences, Sari, Iran. Rabeeh Tabaripour r.tabaripour69@gmail.com 100319475328460013696 100319475328460013696 No Toxoplasmosis Research Center, Communicable Diseases Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Hedieh Hatamipour Hedi.hatami@gmail.com 100319475328460013697 100319475328460013697 No Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran. Fatemeh Mesgarian Mesgariana@yahoo.com 100319475328460013698 100319475328460013698 No Gonabad Health Centre, Golestan University of Medical Sciences, Gonabad, Iran.

en Innate Immune Responses to Leishmania in Dogs and Cats: Mechanisms of Evasion and Host Defense Special Issue: “Leishmaniasis” Special Issue: “Leishmaniasis” review review <div style="text-align: justify;">Background: Leishmaniasis is an infection transmitted by arthropod vectors and is caused by protozoan parasites of the genus Leishmania. Primarily, dogs function as reservoirs. Emerging evidence points to cats as secondary hosts. This study aimed to review innate immune responses and parasite evasion mechanisms in canine and feline leishmaniasis. Methods: This narrative review synthesized peer-reviewed studies on innate immune responses to Leishmania infection in dogs and cats, identified through searches of major biomedical databases (including PubMed, Scopus, and Web of Science) from 1990 to 2025. Eligible articles reported immunological data on innate cells, cytokine profiles, or parasite evasion; non-English publications, case reports, and studies without immune outcomes were excluded. Key findings were qualitatively integrated to compare species-specific responses and associated clinical outcomes. Results: Dogs with progressive disease show mixed Th1-Th2 responses, with IL-10 and TGF-β promoting parasite persistence. Cats more often exhibit dominant Th1 responses, with elevated IL-12 and IFN-γ correlating with greater suppression of parasite growth and subclinical infection. Leishmania evades immunity by inhibiting phagolysosome maturation, modulating Toll-like receptor signaling, and suppressing reactive oxygen and nitrogen species. Cats display lower antibody production than dogs, contributing to their resistance; however, co-infections with retroviruses increase feline susceptibility. -12/IFN-γ-inducing vaccines and therapies targeting IL-10/TGF-β pathways show potential. Conclusion: Distinct innate immune responses shape disease outcomes in dogs and cats, necessitating tailored diagnostic and therapeutic approaches and inclusion of feline leishmaniasis in One Health surveillance.  </div> Cats, Dogs, Leishmania, Macrophages, Parasite Immunology, Toll-Like Receptors, Zoonoses 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1408-1&slc_lang=en&sid=1 Sajede Asghari Sajedehasghari7444@gmail.com 100319475328460013688 100319475328460013688 No Department of Clinical Sciences, Bab.C., Islamic Azad University, Babol, Iran. Mostafa Kami m.kami@mazums.ac.ir 100319475328460013689 100319475328460013689 Yes The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran Najva Zivdari zivdari.na@fv.lu.ac.ir 100319475328460013690 100319475328460013690 No Undergraduate DVM, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran Masoud Abedi masoudabedi80400@vet.uk.ac.ir 100319475328460013691 100319475328460013691 No Undergraduate DVM, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran Fatemeh Sabeti st_f.sabeti@urmia.ac.ir 100319475328460013692 100319475328460013692 No Undergraduate DVM, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

en A Review of Recent Advances in Leishmania Nanovaccines with Emphasis on Liposomal Nanovaccines انگل شناسي Parasitology review review <div style="text-align: justify;">Background: Leishmaniasis remains a significant global health challenge, with no approved human vaccine available. Recent advances in nanotechnology have opened new avenues for vaccine development, offering improved antigen delivery, enhanced immunogenicity, and targeted immune responses. Methods: This review provides a comprehensive overview of recent progress in Leishmania nanovaccines, with a particular focus on liposomal formulations. Results: We discuss the immunological basis for vaccine design, the limitations of conventional vaccines, and the advantages of nano-carrier systems. Liposomal nanovaccines are highlighted for their versatility, biocompatibility, and ability to co-deliver antigens and adjuvants, leading to potent Th1-biased immune responses. We also examined other promising nano-platforms, including polymeric nanoparticles, solid lipid nanoparticles, emulsions, and virus-like particles. Despite promising preclinical results, challenges remain in scalability, stability, and clinical translation. Conclusion: This review underscores the potential of nanovaccines to overcome existing barriers and accelerate the development of effective vaccines against leishmaniasis.</div> Leishmania, nanovaccines, liposomes, vaccine delivery, adjuvants, immunotherapy 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-733-5&slc_lang=en&sid=1 Ahmad Mehravaran 100319475328460013699 100319475328460013699 No 1. Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran. Javad Akhtari javad.akhtari@gmail.com 100319475328460013700 100319475328460013700 No Toxoplasmosis Research Center, Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran Navid Kalkali 100319475328460013701 100319475328460013701 Yes Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.

en In Vitro Antileishmanial Activity of Calotropis procera Extract on Leishmania major Special Issue: “Leishmaniasis” Special Issue: “Leishmaniasis” پژوهشي Research Background: Pentavalent antimonial agents remain the primary therapeutic option for leishmaniasis; however, accumulating evidence highlights significant adverse effects, toxicity concerns, and emerging drug resistance associated with these compounds. Accordingly, the exploration of alternative therapeutic agents, particularly from natural sources, has gained increasing attention. The present study aimed to investigate the in vitro antileishmanial activity of Calotropis procera extract against both promastigote and amastigote forms of Leishmania major. Methods: Methanolic extract of C. procera flowers was obtained through the maceration technique. The antiproliferative activity of the extract on promastigotes was quantified using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and growth inhibition. Results:<a name="_Hlk229420678"> MTT assay findings demonstrated that C. procera extract markedly inhibited the proliferation of L. major promastigotes. The calculated IC50 value for the extract alone was 387.91 μg/mL, whereas the combination of C. procera extract with meglumine antimoniate exhibited enhanced inhibitory activity, yielding an IC50 value of 211.26 μg/mL.</a> Conclusion: The observed inhibitory effects suggest that C. procera possesses promising antileishmanial properties and may represent a potential natural candidate for the development of alternative therapeutic strategies against leishmaniasis.   Amastigote, Promastigote, Calotropis procera, Leishmania major, Extract 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1466-1&slc_lang=en&sid=1 Hadi Mirahmadi hmirahmadi59@gmail.com 100319475328460013685 100319475328460013685 Yes Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran. Ahmad Mehravaran ahmadmehravaran55@gmail.com 100319475328460013686 100319475328460013686 No Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran Abbas Safdari Adimi abbas.saf1347@gmail.com 100319475328460013687 100319475328460013687 No Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran

en Aptamer-Based Biosensors: Emerging Tools for Next-Generation Diagnosis of Strategic Parasitic Diseases Special Issue: “Leishmaniasis” Special Issue: “Leishmaniasis” review review <div style="text-align: justify;">Parasitic diseases impose a profound global health and economic burden, particularly in resource-limited settings where rapid and accurate diagnostic infrastructure is lacking. Traditional diagnostic methods often fall short in sensitivity, specificity, and point-of-care adaptability. Aptamers—single-stranded DNA or RNA oligonucleotides selected in vitro via systematic evolution of ligands by exponential enrichment (SELEX)—have emerged as highly stable, cost-effective, and versatile biorecognition elements capable of binding diverse targets with high affinity and specificity. This review explored the mechanisms of aptamer-based biosensors (aptasensors) and their emerging applications in diagnosing strategic parasitic infections, including malaria, leishmaniasis, Chagas disease, Human African Trypanosomiasis, and giardiasis. Despite challenges, such as nuclease degradation and SELEX-related biases, aptamer-based biosensors demonstrate significant potential as reliable, sensitive, and specific tools for next-generation diagnosis and monitoring of parasitic diseases. </div> Aptamer, Biosensors, Emerging tools, Parasitic diseases 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-183-1&slc_lang=en&sid=1 Rezvan Yazdian Robati yazdianr921@gmail.com 100319475328460013676 100319475328460013676 No Pharmaceutical Sciences Research Center, Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran. Rabeeh Tabaripour r.tabaripour69@gmail.com 100319475328460013677 100319475328460013677 No Toxoplasmosis Research Center, Communicable Diseases Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Mahdi Fakhar mahdifakhar53@gmail.com 100319475328460013678 100319475328460013678 Yes Toxoplasmosis Research Center, Communicable Diseases Institute, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Hajar Ziaei Hezarjaribi ziaei2000@yahoo.com 100319475328460013679 100319475328460013679 No Pharmaceutical Sciences Research Center, Institute of Herbal Medicines and Metabolic Disorders, Mazandaran University of Medical Sciences, Sari, Iran.