Malaria is one of the world's most critical parasitic diseases; it is caused by Plasmodium species and spreads through Anopheles mosquitoes. The life cycle of Plasmodium species is complex and involves several stages in humans and mosquitoes, each involving distinct molecular interactions. Recent molecular biology research has suggested that host microRNAs (miRNAs) may serve as important regulators of host-parasite interactions during malaria infection. MicroRNAs, approximately 22 nucleotides long, are non-coding RNAs that control gene expression by binding to target mRNAs and either repressing translation or causing mRNA degradation. During infection, host miRNAs are actively regulated and can directly target parasite transcripts or influence host cellular pathways essential for parasite survival and disease development. The role of human miRNAs has not yet been fully explored in malaria. This report aims to integrate evidence from the literature, molecular mechanisms, and translational insights to summarize the current knowledge in miRNA research and to guide the diagnosis and treatment of malaria using miRNAs. Here, we focus on the mechanistic and cell-type-resolved dimension of host miRNA action in malaria: the extracellular vesicle-mediated transfer of AGO2-miRNA complexes between infected erythrocytes and recipient endothelial cells, the bidirectional host-parasite miRNA traffic that allows human miRNAs to repress parasite transcripts, and the tissue-specific miRNA programs that shape organ-specific pathology. We also delineate the principal knowledge gaps related to causality versus correlation, cell-of-origin attribution, and translational barriers to miRNA therapeutics that must be resolved before miRNAs can be deployed diagnostically or therapeutically in malaria.

Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Heat shock protein family D member 1 (HSPD1 or HSP60), a multifunctional chaperone, has been implicated in promoting lung cancer progression by regulating tumor cell growth, cancer-associated fibroblast activation, and angiogenesis. Despite these roles, the molecular mechanisms underlying its oncogenic activity remain incompletely understood. In this study, we conducted a proteomic analysis and functional investigations on HSPD1-knockdown and control A549 cells. Knockdown of HSPD1 suppressed cell proliferation, disrupted cell-cycle progression, and had no significant effect on apoptosis. Additionally, HSPD1-knockdown cells exhibited reduced colony formation, wound closure, and invasion capabilities. Sequential Window Acquisition of All Theoretical fragment ions (SWATH)-targeted proteomics revealed 21 significantly altered proteins, primarily involved in ribosome-related functions and associated with overall survival in LUAD patients. Reduced levels of ribosomal proteins and translational capacity were further examined by Western blot and protein synthesis assays. A decrease in ribosome abundance was confirmed by immunofluorescence staining of ribosomal protein S3 (RPS3) and by direct visualization under transmission electron microscopy. Quantitative real-time PCR demonstrated downregulation of MTOR in HSPD1-knockdown cells. Moreover, HSPD1 knockdown sensitized cells to homoharringtonine, a chemotherapeutic drug targeting ribosomal activity. These effects on cell proliferation, ribosomal protein levels, and drug sensitivity were validated in an independent LUAD cell line, H1975. Collectively, these findings indicate that HSPD1 acts as an oncogenic driver in LUAD by modulating ribosome-related pathways and protein synthesis.

Echinococcosis is a parasitic zoonosis caused primarily by Echinococcus granulosus (cystic echinococcosis, CE) and Echinococcus multilocularis (alveolar echinococcosis, AE). While CE typically manifests with well-formed unilocular cysts, AE presents as an infiltrative, tumour-like process. Mixed or atypical presentations pose diagnostic and therapeutic challenges. We describe a 24-year-old man from Morocco residing in Poland, who presented with progressive abdominal distension, pain, and subacute gastrointestinal obstruction. CT and ultrasound revealed multiple large, septated cysts involving the liver, spleen, peritoneum, and right lung. Serological findings were inconsistent across timepoints, alternating between positivity for E. granulosus and E. multilocularis. No molecular confirmation was available at the time of clinical decision-making. Albendazole therapy led to partial regression of intra-abdominal lesions but not pulmonary ones. Radiological findings were compatible with WHO CE2/CE3b stages, yet extensive dissemination and serological fluctuation suggested AE or a mixed pattern. A retrospective research-based molecular analysis later confirmed E. granulosus sensu stricto (G1 genotype), supporting a CE diagnosis. This case emphasizes the diagnostic uncertainty in disseminated echinococcosis with serological discordance and highlights the value of comprehensive diagnostic strategies, especially in-migrant populations from endemic areas and highlights the importance of emerging molecular diagnostics.

The Sicilian Black pig is a well-adapted autochthonous breed, yet its susceptibility to respiratory disease remains poorly defined due to limited data on pathogen circulation and lesion patterns in extensive production systems. This study characterised the pathological features of Porcine Respiratory Disease Complex (PRDC) in this breed by examining lungs and tracheobronchial lymph nodes from 59 animals through pathological assessment, molecular detection of major respiratory pathogens, and evaluation of crystalline particulates using scanning electron microscopy coupled with energy-dispersive X-ray analysis to characterise infectious and environmental contributors. Gross examination revealed multifocal cranioventral bronchopneumonia in 35/59 pigs (59.32%) and diffuse interstitial pneumonia in 18/59 pigs (30.51%). Molecular testing identified Mycoplasma hyopneumoniae (M. hyopneumoniae) as the most frequent pathogen (17/47; 36.17%), followed by porcine circovirus type 2 (PCV2; 10/47; 21.28%) and Pasteurella multocida (6/47; 12.77%), with co-infections consistently involving M. hyopneumoniae. The presence of pathogen DNA was correlated with increased severity of lesions as well as the presence of fibrosis and hyperplasia of the BALT. Histological evidence of Metastrongylus spp. lungworms was identified in 7/35 pigs (20%) with bronchopneumonia. Silicate crystals consistent with pulmonary silicosis were detected in 10/59 lungs (17.0%), indicating substantial exposure to silicate-rich dust in outdoor environments. However, silicosis was not related to the presence of specific respiratory pathogens. Overall, these findings demonstrate that respiratory disease in Sicilian Black pigs is multifactorial, arising from the combined influence of bacterial, viral, parasitic, and environmental components. The concurrent detection of M. hyopneumoniae, PCV2, secondary bacterial agents, lungworm infestation, and silicate particulates supports an integrated PRDC model in this native breed. These results highlight the need for a multifaceted control strategy, including improved diagnostics, targeted management, immunoprophylaxis, helminth control, and mitigation of silicate-rich dust to reduce the impact of PRDC in extensive production systems.

Lophomoniasis is a new emerging parasitic disease caused by Lophomonas spp., a protozoan that predominantly resides in a commensal relationship within the hindgut of cockroaches. This pathogen is known to affect the lower respiratory tract in humans, resulting in clinical manifestations such as cough, sputum production, and shortness of breath. We present two case studies involving a 54-year-old- and a 38-year-old male, both with a history of cigarette smoking but no known underlying medical conditions. These individuals presented at the emergency room with respiratory symptoms and were subsequently evaluated. No significant abnormalities were shown on the lung computed tomography scan in Case 1, whereas empyema was observed in the right lung in Case 2. Analysis of bronchoalveolar lavage fluid from each patient revealed Lophomonas spp., an emerging protozoan pathogen, by microscopic examination. Based on these findings, metronidazole was administered to both patients, resulting in successful treatment of the infection. These cases highlight that Lophomonas spp. is a significant respiratory pathogen capable of causing a spectrum of disease in immunocompetent individuals, from mild bronchitis to severe pneumonia with complications. They emphasize the critical importance of including lophomoniasis in the differential diagnosis for persistent or atypical respiratory infections. Timely treatment with metronidazole was effective, resulting in clinical resolution.

Ras signalling is an important regulator of cell proliferation, survival, differentiation, and immune responses. Although Ras pathways have been extensively studied in cancer biology, increasing evidence suggests that many pathogens also manipulate Ras-associated signalling networks to support infection, persistence, and immune evasion. Viruses, bacteria, and parasites can alter Ras activity either directly or indirectly through downstream pathways such as MAPK/ERK and PI3K/AKT. However, activation of ERK or AKT does not always indicate direct Ras involvement, and this distinction remains important in infectious disease research. Recent studies show that pathogens including SARS-CoV-2, Epstein-Barr virus, hepatitis B virus, Helicobacter pylori, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Leishmania species regulate Ras-associated signalling in ways that contribute not only to pathogen survival but also to inflammation, tissue injury, and disease progression. In several infections, isoform-specific regulation of H-Ras, K-Ras, and N-Ras has also been observed, suggesting distinct roles in immune modulation and pathological outcomes. Dysregulated Ras-associated signalling has been linked to lung injury, liver fibrosis, gastric epithelial damage, granuloma formation, and systemic dissemination of infection. This review summarizes current evidence on the role of Ras signalling in infectious disease pathology, focusing on host-pathogen interactions, isoform-specific regulation, tissue damage, and therapeutic implications. Although Ras signalling represents a promising host-directed target, much of the current evidence remains indirect and requires further pathogen-specific validation.

Animal tuberculosis caused by mycobacteria of the Mycobacterium tuberculosis complex (MTBC) represents a significant challenge to both public and animal health. Although eradication programs focus predominantly on cattle, small ruminants, especially goats, may play a relevant role as reservoirs. This study aimed to characterize tuberculosis cases in small ruminants in Portugal diagnosed at the national reference laboratory for Tuberculosis (Instituto Nacional de Investigação Agrária e Veterinária) over the period from April 2012 to July 2023. In this study, samples from 79 animals suspected of TB (64 goats and 15 sheep) were analyzed by integrating histopathology; bacteriology; and, when applicable, PCR results, thereby allowing the distribution by species to be described, MTBC agents to be identified, and diagnostic agreement to be assessed. Of these samples, 29 positive cases (36.7%) were identified, all of them in goats (45.3% of goats tested), whereas no cases were confirmed in sheep. Mycobacterium caprae was the most frequently identified species (89.7%), followed by Mycobacterium bovis (10.3%). Geographic distribution was concentrated in the Alentejo (48.3%) and Norte (44.8%) regions, where 93.1% of cases occurred. Topographical analysis of lesions revealed respiratory tract involvement (lung and/or thoracic lymph nodes) in 82.7% of positive cases, with gross patterns including caseous/caseocalcified lesions (n = 11), necrosis (n = 9), and nodular granulomatous lesions (n = 10). Agreement between histopathology and bacteriology was 81.5%. Parasitic coinfections were observed in 24.1% of positive cases, complicating histopathological interpretation. The results of this study indicate goats, as opposed to sheep, as non-negligible reservoirs of TB, suggesting species-level differences that warrant targeted investigation. The predominance of respiratory lesions and the detection of extensive cavitary forms indicate potential aerogenous transmission with implications for multi-host systems. Diagnostic discordance and parasitic interference reinforce the need for combined testing methodologies. It is therefore advisable to consider the integration of goats into tuberculosis surveillance and control programs, with greater relevance in Alentejo and Norte.

Local immune cell activation and vascular remodelling are characteristic pathogenic features of pulmonary arterial hypertension (PAH). HIV and schistosome infections have been individually associated with PAH. However, whether co-infection with these pathogens has a distinct impact on the development of pulmonary vascular disease remains poorly understood, partly due to the lack of experimental animal models. In a novel non-infectious model of HIV and Schistosoma pulmonary co-exposure based on lung embolisation of S. mansoni eggs in HIV-transgenic (HIV) mice, we previously reported exacerbated endothelial remodelling and dysfunction, along with increased pulmonary arterial pressure; which were associated with a unique profile of pro-inflammatory cytokines in the lung. In the present study, we used flow cytometric analysis of isolated lung leukocytes and immunofluorescence staining to characterise the pulmonary immune cell landscape associated with individual or combined exposure to HIV and schistosome. Compared with mice exposed to HIV (untreated HIV mice) or schistosome (egg-treated wild-type mice), co-exposed (egg-treated HIV mice) animals showed significantly increased numbers of interstitial and alveolar macrophages, patrolling-type monocytes, NKT and γδ T cells, and reduced CD8[+] αβ T cells. Other lung immune cells, including inflammatory-type monocytes, eosinophils/neutrophils, dendritic cells, CD4[+] αβ T cells, NK cells and B cells were not significantly affected in the co-exposure condition. Taken together, these results show for the first time that combined pulmonary exposure to HIV and Schistosoma, as it may occur in co-infected individuals, alters the local immune cell landscape in a manner distinct from that of individual exposure. Furthermore, these findings may contribute to a better understanding of the complex inflammatory processes involved in the pathogenesis of PAH, thereby supporting the development of therapies targeting pathogenic immune cells in pulmonary vascular disease associated with HIV and Schistosoma co-morbidity.

Atopic diseases arise from an immunological imbalance where regulatory mechanisms are unable to preserve or restore homeostasis, leading to chronic inflammatory conditions affecting epithelial organs. This may involve homeostasis, deficient or insufficient regulatory T cells (Tregs) or other aberrant regulatory mechanisms. Type 2 (T2) immunity is a conserved response that evolved to combat large helminth parasites (worms), venoms, and toxins involving both innate and adaptive immune pathways. Many T2 cytokines and alarmins act to recruit and activate innate and adaptive immune cells, and they also lead to mucous production, hyperplasia, and tissue remodeling. These responses were designed to enhance expulsion of parasites, repair the barrier and elicit protective mechanical reflexes such as scratching or coughing. Today, with reduced parasitic exposure serving as an opposing influence on T2 immunity, it is hypothesized that T2 responses may be triggered by low amounts of environmental stimuli in genetically susceptible individuals, leading to unchecked T2 inflammation and atopic diseases at multiple barrier surfaces. This paper reviews the evidence linking host T2 immunity with T2 inflammatory mechanisms in atopic diseases and explores the hypothesis that these diseases may be perpetuated from a central imbalance between Th2 vs. Th1, Th3, and Tregs, influenced by tissue-dependent, local environmental-insult-driven innate cell responses, interconnected by a cycle of self-amplifying cytokine signaling.

Visceral leishmaniasis (VL) is a systemic parasitic disease that predominantly involves the reticuloendothelial system, with pulmonary involvement being distinctly uncommon, particularly in individuals who are immunocompetent. We report a case of a middle-aged female who was immunocompetent presenting with acute hypoxaemic respiratory failure, characterised by progressive dyspnoea, bilateral lung consolidation and pleural effusion, initially mimicking severe pulmonary infection or haematological malignancy. The presence of pancytopenia, hypergammaglobulinaemia and massive hepatosplenomegaly raised suspicion of an underlying systemic disorder. Definitive diagnosis was established by demonstration of Leishmania donovani amastigotes in splenic aspirate, with further confirmation of direct pulmonary involvement through identification of intracellular amastigotes within alveolar macrophages on a transbronchial lung biopsy. The patient showed significant clinical and radiological improvement following treatment with liposomal amphotericin B and miltefosine. This case highlights that VL can rarely present with primary pulmonary manifestations even in immunocompetent hosts. It underscores the importance of considering VL in the differential diagnosis of unexplained pulmonary infiltrates with systemic features in endemic regions and demonstrates that histopathological confirmation from lung tissue can be crucial in establishing pulmonary involvement in atypical presentations.