Leishmaniases, neglected tropical diseases comprising diverse clinical forms and manifestations depending upon the causative Leishmania species, remain a major public health concern globally. Broadly, the diseases are classified into cutaneous (CL), mucocutaneous (MCL) and visceral (VL) forms based on tissue invasion and pathogenesis. Conventional therapeutic agents, including antimonial compounds, amphotericin B, miltefosine, pentamidine, and paromomycin, are limited by high toxicity, emerging resistance, and poor bioavailability. Leishmania amastigotes proliferate within macrophages of the reticuloendothelial system, posing a significant challenge for effective drug delivery. Recent advancements in novel drug delivery systems (NDDS) incorporating diverse nano-formulations offer promising solutions by enhancing targeting efficiency and reducing systemic side effects. This review evaluates current literature (2000-2025) regarding NDDS applications against CL (including MCL) and VL. While formulations like AmBisome are clinically established, many others remain in preclinical stages. This paper critically analyzes the transition from conventional to novel therapies, the mechanisms of intracellular delivery, and the regulatory hurdles delaying clinical translation.

Staphylococcus aureus is a leading cause of antibiotic-resistant infections worldwide. Therefore, there is a constant need to develop new growth inhibitors. Pentamidine analogs (PAs) composed of thiourea-linked amidines were evaluated for activity against methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria. S. aureus, MRSA, Staphylococcus epidermidis, Streptococcus pyogenes, Mycobacterium, and Bacillus were highly susceptible with minimal inhibitory concentration (MIC) values ranging from 1.56 to 6.25 μM, whereas Enterococcus species and Clostridioides difficile were not as susceptible with MICs of 50 to ≥100 μM. For S. aureus, MRSA and VISA strains, PAs showed ∼4-fold lower MICs when compared to pentamidine (PNT). The concentration of PAs needed to lyse 50% of red blood cells (HC50) was ∼16-32-fold higher than their corresponding MICs. For PNT, a lower HC50/MIC range of 1.25-5 was observed. Approximately 60% of MRSA was cleared from infected Caenorhabditis elegans by the PAs. PAs also provided 100% protection in a septicemia model of infected mice. Morphological changes induced by these compounds indicate disruption of cell membrane integrity, where >80% of treated bacterial cells took up propidium iodide in a permeation assay. Importantly, there was a lack of resistance observed with the PAs, compared to the fairly rapid and stable resistance occurrence for drugs commonly used to treat S. aureus infection. These results reflect the potential of such compounds as potential new tools to optimize and combat the menace of drug-resistant S. aureus.

American tegumentary leishmaniasis (ATL) remains a significant public health problem in the Americas, with the Amazon region standing out in Brazil for its high number of cases. This article aimed to present advances in the understanding of epidemiology, diagnosis, treatment and control of ATL in the state of Amazonas over the past decades. This study is a narrative review of scientific studies published in the literature between 2011 and 2025, retrieved from databases such as PubMed and SciELO, as well as public data from the Notifiable Diseases Information System (SINAN), official reports from the Ministry of Health and technical notes from the Amazonas Health Surveillance Foundation. The evolution of disease incidence is reported, highlighting the predominance of Leishmania (Viannia) guyanensis and the environmental factors associated with the increase in cases, such as deforestation and unplanned urbanization. Advances in diagnostic strategies include the expanded use of molecular techniques and the strengthening of the primary healthcare network. Regarding therapy, clinical trials with drugs such as pentamidine, miltefosine, tamoxifen and itraconazole have demonstrated their efficacy in treatment. The review also includes socio-environmental, genetic and experimental studies that have contributed to a better understanding of the disease. It emphasizes the need to establish a priority agenda that includes the use of telemedicine and the institutionalization of collaborative research for therapeutic innovation, integration between research and healthcare services and strategies adapted to the Amazonian context. Regional scientific advances can support more effective control policies and reduce the burden of ATL in this highly endemic setting.

Fibrinolysis assessment is critical for diagnosing and managing clinical blood disorders. Currently available viscoelastic testing platforms provide an overview of global coagulation and fibrinolysis profiles but lack fibrinolysis specific assessment of a preformed clot substrate. The lack of a sensitive, standardized testing platform for fibrinolysis assessment can limit risk stratification and the management of blood disorders. We describe herein the plasma annular clot lysis assay. The assay adapts the previously standardized FITC-tagged fibrin annular clot assay to plasma obtained from healthy human donors. Plasmin at concentrations ranging from 200-800 nM was used as a direct thrombolytic to assess fibrinolysis in plasma-derived annular clots. The Maximum Fibrinolysis Rate (VMFR), FLU200, T90, and MaxFLU were calculated via tracking of the clot digestion curve over time. VMFR was correlated with plasma thromboelastography (TEG) parameters to compare with the global viscoelastic testing system. Additionally, plasma annular clot digestion was monitored in the presence of pentamidine to assess drug-specific effects on fibrinolysis tracking. Plasma annular clots linearly tracked fibrinolysis with increasing plasmin concentration. VMFR across multiple tested plasmin concentrations showed a moderate to strong negative correlation (0.58-0.74) with the observed maximum amplitude from plasma TEG. In the presence of pentamidine (75 µM), the assay was sensitive to identifying differences in the VMFR across treatment groups. Plasma annular clots provide a platform for fibrinolysis evaluation using a patient's own plasma to assess therapeutic dosing clinically in addition to testing novel therapeutics preclinically to further understand mechanistic aspects of fibrinolysis.

Renal cell carcinoma (RCC) is a highly vascularized and metastatic malignancy of the kidney. The 5-year overall survival rate of RCC patients remains poor despite the development of therapeutic modalities. Therefore, identifying novel approaches to increase the sensitivity of RCC cells to drugs could help prolong patient survival. Recently, Drug repurposing, which leverages the established safety profiles and pharmacological properties of existing medications, has emerged as a promising alternative to traditional drug development. This approach can accelerate the translation of new therapies into clinical practice and is often associated with lower attrition rates in clinical trials. Recent evidence supports the therapeutic potential of various repurposed drugs against RCC. This review article summarizes and shows the effectiveness and potential of repurposed drugs including metabolic and cardiovascular modulators (metformin, simvastatin), antimicrobial and antiparasitic agents (artesunate, ivermectin, ketoconazole, chloroquine, hydroxychloroquine, niclosamide, doxycycline, pentamidine), mTOR inhibitors (temsirolimus, everolimus, rapamycin), anti-inflammatory and analgesic agents (aspirin, celecoxib), and agents with other mechanisms of action (acetazolamide, disulfiram). These agents exert their anticancer effects against RCC by modulating multiple signaling pathways, including PI3K/AKT/mTOR, AMPK, JAK2/STAT3, ERK1/2, Wnt/β-catenin, and RhoA/ROCK, as well as by inducing autophagy inhibition, ferroptosis, oxidative stress, and mitochondrial dysfunction, highlighting their utility in RCC therapy and emphasizing their clinical relevance.

Multidrug-resistant (MDR) Acinetobacter baumannii is a WHO priority pathogen that endures in hospitals and complicates care in intensive care units. Drug repositioning offers a faster path to therapies by reusing approved agents with known safety. This review compiles in vitro and in vivo evidences for repurposed candidates against MDR A. baumannii. Repurposing of anticancer drugs displayed bacterial load reduction and enhancement of polymyxin B through membrane permeabilization. Additionally, antiparasitics increased colistin efficacy by altering surface charge. Furthermore, central nervous system (CNS) agents contributed synergy with traditional antibiotics. Anti-inflammatory and other agents also showed promise: diclofenac enhanced colistin killing, desloratadine blocked growth and synergized with meropenem, and auranofin paired with pentamidine achieved bactericidal effects. Translating these signals will require attention to dosing, delivery, and safety, and rigorous clinical trials. In total, repurposing, particularly in rational combinations, could supply near-term options for severe MDR A. baumannii infections.

BACKGROUND: Cerebral toxoplasmosis is a rare but potentially fatal opportunistic infection in non-HIV immunocompromised patients, particularly after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis is often delayed due to nonspecific clinical manifestations. CASE PRESENTATION: We report a 66-year-old man with myelodysplastic syndrome that had transformed into secondary acute myeloid leukemia. Following remission induction with CPX-351, he underwent allo-HSCT and received ciclosporin A, mycophenolate mofetil, and corticosteroids for graft-versus-host disease prophylaxis. Standard cotrimoxazole prophylaxis was withheld because of hepatic intolerance and thrombocytopenia, and inhaled pentamidine was administered instead. Three months post-transplant, the patient presented with bilateral visual field deficits. Automated perimetry revealed a homonymous inferior quadrantanopia. Brain MRI demonstrated a solitary ring-enhancing lesion in the left optic radiation, and cerebrospinal fluid PCR confirmed Toxoplasma gondii. Treatment with sulfadiazine, pyrimethamine, and folinic acid was initiated, followed by long-term secondary prophylaxis. Despite residual visual impairment, the patient achieved clinical stability. CONCLUSION: This case underscores the diagnostic value of neuro-ophthalmologic examination and early neuroimaging in detecting opportunistic CNS infections. It also highlights the challenges of prophylactic decision-making in immunocompromised patients when cotrimoxazole is contraindicated. Individualized immunosuppressive and prophylactic strategies, along with multidisciplinary care, were key to successful management.