Explore the vast range of titles available.

The medicinal leech, Hirudo medicinalis , is an excellent example of the use of invertebrates in the treatment of human disease. Utilized for various medical indications since the ancient times, the medicinal leech is currently being used in a narrow range of well-defined and scientifically-grounded clinical applications. Hirudotherapy is most commonly used in the setting of venous congestion associated with soft tissue replantations and free flap-based reconstructive surgery. This is a comprehensive review of current clinical applications of hirudotherapy, featuring a comprehensive search of all major medical search engines (i.e. PubMed, Google Scholar, ScientificCommons) and other cross-referenced sources. The authors focus on indications, contraindications, practical application/handling of the leech, and therapy-related complications.

This study aimed to investigate the histological and morphological differences between healthy and deformed specimens of the medicinal leech , with particular focus on tissue integrity and cellular organization. We conducted comparative histological analysis using haematoxylin and eosin staining on tissue sections obtained from both healthy and deformed leeches. The evaluation included examination of epithelial layer integrity, muscle tissue organization, secretory cell distribution, and pigment accumulation patterns. Healthy specimens demonstrated well-preserved epithelial layers with regularly arranged circular and longitudinal muscle fibers. The secretory cells (T1, T2A, and T2B types) maintained normal distribution and activity, while melanin pigment showed limited and organized deposition in connective tissues. In contrast, deformed leeches exhibited significant structural abnormalities including disrupted epithelial layers, disorganized muscle architecture (particularly in circular muscles), and reduced T2B secretory cell populations. Notable accumulation of mononuclear immune cells, accompanied by increased melanin deposition, was observed in association with inflammatory foci. Morphological abnormalities included body segmentation defects, tissue atrophy, functional impairment of suckers, and compromised mobility. Our findings demonstrate that deformation in leads to substantial histological and morphological alterations affecting epithelial integrity, muscular organization, secretory functions, and pigmentation patterns. These changes may significantly impact the leeches' biological functionality and therapeutic potential. Further investigation using immunohistochemical techniques and molecular analyses are warranted to elucidate the underlying mechanisms of these pathological changes.

Although the European medicinal leech ( Hirudo medicinalis L. 1758) is one of the best-known members of the Hirudinea due to its use in phlebotomy, this species has been confused with the Mediterranean taxon Hirudo verbana Carena 1820. Here we describe the morphology of adult and juvenile Hirudo medicinalis and document its genetic distance to Hirudo verbana , using newly acquired mitochondrial DNA-sequence (cytochrome c oxidase subunit I, CO-I)-data from specimens collected in Germany. Our CO-I analysis shows that Hirudo medicinalis and Hirudo verbana differ by 9.4 %. Hence, the original Hirudo -population diverged ca. 10 million years ago so that today two geographically separated biospecies exist that co-occur in only a few natural habitats. We analyzed the behaviour of adult Hirudo medicinalis , but could not find differences with respect to its sister taxon Hirudo verbana . Finally, we summarize the occurrence of Hirudo medicinalis in Central Europe and conclude that this once widely distributed freshwater species largely disappeared in many countries. We suggest that the loss of natural freshwater ecosystems, with flat, warm banks, and amphibians (frogs, newts and toads) as preferred host organisms for the juveniles, are largely responsible for the decline of Hirudo medicinalis in Northern Europe.

The growing threat of infectious diseases requires novel therapeutics with different mechanisms of action. Antimicrobial peptides (AMPs), which are crucial for innate immunity, are a promising research area. The medicinal leech (Hirudo medicinalis) is a potential source of bioactive AMPs that are vital while interacting with microorganisms. This study aims to investigate the antimicrobial properties of peptides found in the H. medicinalis genome using a novel high-throughput screening method based on the expression of recombinant AMP genes in Escherichia coli. This approach enables the direct detection of AMP activity within cells, skipping the synthesis and purification steps, while allowing the simultaneous analysis of multiple peptides. The application of this method to the first identified candidate AMPs from H. medicinalis resulted in the discovery of three novel peptides: LBrHM1, NrlHM1 and NrlHM2. These peptides, which belong to the lumbricin and macin families, exhibit significant activity against E. coli. Two fragments of the new LBrHM1 homologue were synthesised and studied: a unique N-terminal fragment (residues 1–23) and a fragment (residues 27–55) coinciding with the active site of lumbricin I. Both fragments exhibited antimicrobial activity in a liquid medium against Bacillus subtilis. Notably, the N-terminal fragment lacks homologues among previously described AMPs.

Background/Objectives: Leeches constitute a pharmacologically significant animal group in traditional medicine due to their antithrombotic peptides, which include numerous members of the hirustasin gene superfamily. However, a comparative expression profile of this pharmaceutically important family across different leech species is lacking. Methods: This study conducted a comparative transcriptomic analysis of hirustasin gene superfamily expression in the hematophagous leech Hirudinaria manillensis and the non-hematophagous leech Whitmania pigra. Results: The total expression of the hirustasin gene superfamily, quantified as transcripts per million (TPM), showed no significant difference (p = 0.237) between H. manillensis (11,802.60 ± 1596.59) and W. pigra (8623.12 ± 965.96). However, both species exhibited pronounced intergenic expression heterogeneity. Five dominantly expressed genes (TPM > 1000) in H. manillensis and three in W. pigra were identified, collectively comprising 81% and 62% of the total hirustasin gene superfamily expression per species, respectively. Critically, the dominantly expressed genes exhibited no phylogenetic correspondence between species. Integrating expression profiles with phylogenetic reconstruction identified five high-potential candidate genes: poecistasin_Hman2, hirustasin_like_Hman01, hirustasin_like_Hman11, guamerin_Wpig, and bdellastasin_Wpig. Population-level analysis revealed marked population-specific expression patterns in H. manillensis, contrasting with minimal inter-population divergence in W. pigra. Nevertheless, geographically distinct populations of both species showed significant variation in the expression of their respective dominantly expressed genes. Conclusions: These findings provide a set of high-priority candidate genes and insights into their expression characteristics, serving as a starting point for subsequent functional validation and, when integrated with other screening methods, for future antithrombotic drug discovery.

Hirudo nipponia (known as Shui Zhi in Chinese) is a well-known Chinese medicine with numerous active ingredients in its body, especially in its saliva. This native Chinese blood-sucking leech has been used for therapeutic purposes since before 100 AD. Modern Chinese physicians use it for a wide range of diseases. Genomic data and molecular information about the pharmacologically active substances produced by this medicinal leech are presently unavailable despite this organism's medicinal importance. In this study, we performed transcriptome profiling of the salivary glands of medicinal leech H. nipponia using the Illumina platform. In total, 84,657,362 clean reads were assembled into 50,535 unigenes. The obtained unigenes were compared to public databases. Furthermore, a unigene sequence similarity search and comparisons with the whole transcriptome of medical leech were performed to identify potential proteins. Finally, more than 21 genes were predicted to be involved in anticoagulatory, antithrombotic, antibacterial, anti-inflammatory and antitumor processes, which might play important roles in the treatment of various diseases. This study is the first analysis of a sialotranscriptome in H. nipponia. The transcriptome profile will shed light on its genetic background and provide a useful tool to deepen our understanding of the medical value of H. nipponia.

As life expectancy continues to increase, age-related disorders are becoming more prevalent. Among these, vascular complications resulting from chronic inflammation are particularly concerning, as they impair angiogenesis and hinder tissue repair, both processes that heavily rely on a well-structured extracellular matrix (ECM). In this context, MicroMatrix® UBM Particulate, a skin substitute composed of collagen, laminin, and proteoglycans, appears to offer properties conducive to tissue regeneration. The aim of this study was to evaluate the regenerative potential of MicroMatrix® combined with the Secretome of human Dental Pulp Stem Cells (hDPSC-S), using the medicinal leech Hirudo verbana, a well-established model for studying wound healing, angiogenesis, and tissue regeneration. Adult leeches were injected with MicroMatrix® either suspended in FBS-free medium (CTRL) or supplemented with hDPSC-S. 1-week post-treatment, the animals were sacrificed and subjected to morphological and immunohistochemical analyses. Our findings revealed that MicroMatrix® successfully integrated into the leech body wall. Notably, when supplemented with hDPSC-S, there was a marked increase in cell infiltration, including telocytes and Hematopoietic Precursor Stem Cells, along with a significantly higher vessel density compared to CTRL. These results support the effectiveness of the cell-free device composed of MicroMatrix® and hDPSC-S, highlighting its potential as a promising strategy for regenerative therapies aimed at treating complex wounds with poor vascularization.

Thrombosis triggers various severe diseases, while antithrombotic drugs carry bleeding risks, making the development of novel natural anticoagulants a subject of widespread attention. Poecilobdella manillensis , a prevalent medicinal leech, exhibits remarkable anticoagulant and antithrombotic activities. However, the material basis underlying its anticoagulant effects remains insufficiently investigated. This study aims to mine anticoagulant peptides from P. manillensis by peptidomics analysis, elucidate the material basis of its anticoagulant activity, and provide candidate molecules for developing novel natural anticoagulant drugs. Proteins extracted from P. manillensis were enzymatically digested and fractionated using DEAE-52 and CN columns. The resulting peptide components were analyzed by UPLC-Q-Orbitrap HRMS, and peptide sequences were matched against proteomic databases using Proteome Discoverer. Anticoagulant peptides were predicted using the BIOPEP-UWM database and PeptideRanker server, followed by in vitro and in vivo activity validation. Results showed that the hydrolysate consisted predominantly of low-molecular-weight peptides. 1533 peptides with Mw < 3000 Da (length < 20 amino acids) were identified from the PM-A2 and PM-A3 fractions, accounting for 40.76% of the total. Four peptides selected through predictive screening demonstrated anticoagulant and antithrombotic activities in vitro. Among them, LE-11 significantly prolonged both APTT and TT ( P  < 0.0001). Furthermore, LE-11 effectively alleviated carrageenan-induced thrombosis in mice, outperforming the heparin control at the mid-concentration (20 mg/kg). In this study, the highly active anticoagulant peptide LE-11 was identified from P. manillensis through peptidomic analysis. These findings establish a solid foundation for developing anticoagulant drugs from this source and provide critical scientific support for its clinical application in treating thrombotic diseases. Graphical Abstract

Cationic antimicrobial peptides (CAMPs) are considered as next-generation antibiotics with a lower probability of developing bacterial resistance. In view of potential clinical use, studies on CAMP biocompatibility are important. This work aimed to evaluate the behavior of synthetic short CAMPs (designed using bioinformatic analysis of the medicinal leech genome and microbiome) in direct contact with blood cells and plasma. Eight CAMPs were included in the study. Hemolysis and lactate dehydrogenase assays showed that the potency to disrupt erythrocyte, neutrophil and mononuclear cell membranes descended in the order pept_1 > pept_3 ~ pept_5 > pept_2 ~ pept_4. Pept_3 caused both cell lysis and aggregation. Blood plasma and albumin inhibited the CAMP-induced hemolysis. The chemiluminescence method allowed the detection of pept_3-mediated neutrophil activation. In plasma coagulation assays, pept_3 prolonged the activated partial thromboplastin time (APTT) and prothrombin time (at 50 μM by 75% and 320%, respectively). Pept_3 was also capable of causing fibrinogen aggregation. Pept_6 prolonged APTT (at 50 μM by 115%). Pept_2 was found to combine higher bactericidal activity with lower effects on cells and coagulation. Our data emphasize the necessity of investigating CAMP interaction with plasma.

The digestive tract of medicinal leeches from commercial suppliers has been investigated previously and comprises of a relatively simple bacterial community. However, the microbiome of medicinal leeches collected directly from the natural habitat has not been examined. In this study, we characterized the bacterial community in the digestive tract (anterior crop, posterior crop, and intestine) of the European medicinal leech, Hirudo verbana, collected from the Danube river using culture-independent and culture-dependent approaches. Culture-independent approach confirmed that the digestive tract of H. verbana carries a relatively simple bacterial community with species richness in the individual samples ranging from 43 to164. The dominant bacterial taxon was Mucinivorans sp. (49.7% of total reads), followed by Aeromonas sp. (18.7% of total reads). Several low abundance taxa, new for H. verbana, such as Phreatobacter, Taibaiella, Fluviicola, Aquabacterium, Burkholderia, Hydrogenophaga, Wolinella, and unidentified Chitinophagia, were also detected. The aerobic culturing approach showed Aeromonas veronii (Proteobacteria), the known leech symbiont, as the most dominant taxon followed by several Pseudomonas and Acidovorax spp. No significant differences in the bacterial community composition were detected among different parts of the digestive tract of individual leeches. However, the overall composition of the bacterial community among individual specimen varied significantly and this is possibly due to differences in leech age, feeding status, and blood source. Our results showed that the core bacterial community of H. verbana collected from the natural habitat is similar to that reported from the digestive tract of commercially supplied leeches maintained in the laboratory.