Search Results (161)

Hyperlipidemia (HL) is a major metabolic disorder and a critical risk factor for cardiovascular diseases, closely associated with oxidative stress, inflammation, and disrupted cholesterol homeostasis. Freeze-dried Poecilobdella manillensis powder (FDPMP), a traditional medicinal product, has shown therapeutic potential against hyperlipidemia; however, its underlying mechanisms remain largely unclear. In this study, HL was induced in ApoE^−/− mice by feeding a high-fat diet (HFD) for eight weeks, during which FDPMP or simvastatin (positive control) was orally administered daily. Concurrently, an in vitro foam cell model was established by exposing RAW264.7 macrophages to oxidized low-density lipoprotein (ox-LDL, 80 μg/mL) for 24 h, with FDPMP pretreatment applied 30 min prior to ox-LDL stimulation. Following intervention, serum lipid profiles, hepatic oxidative stress markers, histopathological changes, and cholesterol metabolism-related gene and protein expression were systematically evaluated. FDPMP administration significantly improved serum lipid profiles by reducing triglycerides, total cholesterol, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol levels. Additionally, FDPMP alleviated histopathological damage in the liver, kidney, and heart, enhanced antioxidant enzyme activities, and attenuated oxidative stress. Untargeted metabolomic analysis revealed that FDPMP markedly modulated key metabolic pathways, including choline metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. Mechanistically, FDPMP restored cholesterol homeostasis through dual regulation of cholesterol metabolism, characterized by upregulation of cholesterol 7α-hydroxylase (CYP7A1) to promote bile acid-mediated cholesterol excretion, alongside downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and synthase (HMGCS1) to inhibit cholesterol biosynthesis. In vitro, FDPMP effectively suppressed ox-LDL-induced foam cell formation, reduced intracellular lipid accumulation, and mitigated oxidative stress in macrophages. Collectively, these findings demonstrate that FDPMP ameliorates hyperlipidemia through coordinated regulation of cholesterol synthesis and excretion, coupled with systemic metabolic reprogramming and antioxidative effects. This study provides mechanistic insights supporting FDPMP as a promising natural therapeutic candidate for hyperlipidemia and related metabolic disorders. Full article

Anthropogenic particles (APs), including suspected microplastics, are increasingly reported in freshwater ecosystems; however, baseline data remain limited for culturally important freshwater fish in the Mississippi River Headwaters. This study assessed the occurrence and morphology of APs in Ogaa (walleye; Sander vitreus) and Asaawe (yellow perch; Perca flavescens) collected from five northern Minnesota lakes. Gastrointestinal tract, liver, and fillet tissues from 49 fish were processed using a modified hydrogen peroxide digestion protocol and examined by stereomicroscopy. Because polymer confirmation was not conducted, visually identified particles are conservatively reported as anthropogenic particles rather than confirmed microplastics. Forty-one APs were identified across all tissues, with 43% of fish containing at least one particle ($0.83\pm 1.$ particles per fish). Fibers were the predominant morphology, followed by fragments, and walleye exhibited greater AP prevalence and abundance than yellow perch. Although descriptive differences were observed among lakes and tissues, statistical analyses did not detect significant relationships among the variables examined. These findings establish baseline information on AP occurrence in culturally important freshwater fish from the Mississippi River Headwaters and provide a foundation for future investigations incorporating polymer confirmation and expanded spatial and temporal sampling. Full article

Background and objectives: A migraine is a highly prevalent and disabling neurological disorder that mainly affects women of childbearing age. Treatment options for migraine prevention are limited during pregnancy and breastfeeding. Although OnabotulinumtoxinA (OnabotA) has proven efficacy and safety in chronic migraine prophylaxis in adults, its safety in pregnancy and breastfeeding remains understudied. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, this review systematically appraised the evidence on the use of OnabotA for chronic migraines and other neurological conditions during pregnancy and breastfeeding across four electronic databases between January 2000 and December 2025. Results: In summary, of the 555 OnabotA-exposed pregnancies, 80.2% resulted in full-term births, with a 17.5% loss rate (73 spontaneous, 21 elective, three unspecified) and 1.6% reporting foetal anomalies. These findings align with general population baselines for miscarriages (12.5–18.7%) and foetal anomalies (3–5%), respectively. Among 94 cases of reported breastfeeding, no adverse infant events or developmental delays were observed at 1 year. Maternal outcomes showed favourable symptom control without adverse effects. Conclusions: Although there is limited data on the use of OnabotA in pregnancy and breastfeeding, no significant adverse effects have been identified in pregnant mothers or neonates. OnabotA should therefore be considered on a case-by-case basis for treatment of various neurological conditions, including migraines, when there are no better safe alternatives. Full article

Climate change is altering the potential distribution of many butterfly species, but climatic suitability alone may be insufficient to sustain the long-term viability of host-dependent butterflies. For papilionid butterflies, larval feeding and development depend on specific host plants; however, the extent to which host plant availability modifies projected suitable habitats under climate change remains unclear. Here, we first selected three threatened papilionids in China: Luehdorfia chinensis Leech, Teinopalpus imperialis Hope, and Troides aeacus C. & R. Felder (Lepidoptera: Papilionidae). Then we constructed two sets of ensemble distribution models: an environment-only model (Env-only) and a host-inclusive model (Env+Host), and compared the resulting projections for each species under current and future climate scenarios (the 2050s, 2070s, and 2090s under SSP1–2.6, SSP2–4.5, and SSP5–8.5). Landscape pattern metrics were further employed to assess changes in the spatial structure of suitable habitats. In the Env-only models, precipitation-related variables were identified as the primary factors constraining the potential distributions of all three species. After it was incorporated, host plant availability became the most important predictor for L. chinensis (41.54%) and T. aeacus (51.53%). In contrast, precipitation of the warmest quarter remained the dominant predictor for T. imperialis (36.00%). Compared with the Env-only models, the Env+Host models forecast smaller suitable habitats for all three species under all scenarios. T. imperialis exhibited the largest host-related contraction under SSP5–8.5 2090s (68.44%). Additionally, landscape pattern metrics indicated increased habitat fragmentation for L. chinensis and T. imperialis, but enhanced spatial continuity for T. aeacus. Overall, the three species have pronounced interspecific differences in their responses to the incorporation of host plant availability. These findings suggest that biotic factors should be incorporated into suitable habitat assessments for threatened papilionids in China. Accordingly, conservation strategies should be tailored to their host specificity, climate-driven distribution, and habitat requirements. Full article

Invasive species represent a major threat to global biodiversity, highlighting the need for continuous monitoring and research to better understand their ecology, distribution, and invasion dynamics. Among freshwater leeches (Hirudinea), Helobdella europaea is considered one of the most successful and widespread invasive taxa. This study provides an updated assessment of the distribution of H. europaea in Morocco and identifies the main environmental factors influencing its occurrence and spread across the country. Field surveys were conducted between 2014 and 2024 in northern Morocco, with particular focus on protected wetlands, including Ramsar sites, and major biogeographical barriers such as the Middle Atlas Mountains and the Sebou and Moulouya river basins. Specimens were collected using Surber samplers (20 × 25 cm, 400 μm mesh), while physicochemical water parameters and other abiotic variables were simultaneously recorded. Since its first detection in Morocco in 2014, H. europaea has significantly expanded its geographic range. The species exhibited broad ecological tolerance, occurring in a wide variety of habitats, including environmentally degraded sites, and enduring substantial variation in water conditions. Among the environmental variables examined, water velocity and salinity were identified as the primary factors constraining the species’ distribution and abundance. Nevertheless, additional studies are required to better predict the future expansion dynamics of H. europaea, particularly under ongoing hydrological alterations and climate change scenarios. Full article

Cystatins from hematophagous organisms modulate host proteases and are promising biotechnological tools. CysHv, a secreted cystatin from the Brazilian leech Haementeria vizottoi, was previously characterized as a potent inhibitor of papain and cathepsin L. In this work, it is shown that its inhibitory activity is tightly linked to conformational state. CysHv is purified as an active monomer but forms inactive dimers in a time-, temperature-, and concentration-dependent manner. A domain-swapping-like mechanism was hypothesized, and a disulfide-engineered mutant restricting local flexibility remained predominantly monomeric, supporting the role of conformational plasticity. Dimer formation correlates with loss of inhibitory activity and is accelerated at acidic pH, suggesting that pH modulates the kinetics rather than triggering dimerization. Comparative structural analysis of cystatins from hematophagous organisms revealed recurrent pairs of oppositely charged residues in β-strands flanking the inhibitory loop in secreted cystatins, but these pairs are generally absent in intracellular homologs. Although causality cannot be established and additional determinants likely contribute to dimerization, this pattern is consistent with pH-sensitive modulation of conformational behavior. Together, these findings identify CysHv as a dimer-prone cystatin for which oligomerization, potentially via a domain-swapping-like mechanism, could act as an environment-dependent regulator of inhibitory activity. Full article

M8OI is a cytotoxic methylimidazolium ionic liquid solvent through its binding to the ubiquinone binding site on complex I of the mitochondrial electron transport chain. Given the overlap in terms of toxic mechanism of action with the pesticide rotenone, the potential neurotoxic effects of M8OI were examined. In vitro, cytotoxicity and mitochondrial function were assessed in SH-SY5Y cells by measuring MTT reduction and oxygen consumption/extracellular acidification using a Seahorse analyser. SH-SY5Y cells were sensitised to M8OI toxicity by replacing medium glucose with galactose. Glucose protected the cells from M8OI toxicity, whereas galactose showed no clear dose–response protection. M8OI induced a dose-dependent reduction in oxygen consumption rate with a compensatory increase in extracellular acidification rate, consistent with inhibition of mitochondrial oxidative phosphorylation and a shift toward glycolysis. In vivo, rats were orally exposed via drinking water for 20 weeks and assessed using behavioural tests. In addition, the concentrations of M8OI and its metabolites were quantified by LC–MS in rat brain and other tissues. In rats, M8OI concentrations were ~30-fold higher in kidney than brain, and brain levels were at least 100-fold lower than the concentrations that affected SH-SY5Y cell viability in vitro. However, based on open field tests, M8OI exposure suppressed motor activity without any anxious behaviours. The cytotoxicity of M8OI in SH-SY5Y neuroblastoma cells was associated with metabolic mitochondrial dysfunction. However, the neurobehavioural changes observed in orally exposed rats occurred at significantly lower brain concentrations than would be predicted to lead to neural cell death. Nevertheless, direct comparisons between acute in vitro exposures and chronic in vivo outcomes should be interpreted cautiously. Full article

Skin injuries are common and can result from surgeries, burns, pressure sores, cuts, and diseases. Proper wound healing is crucial for maintaining homeostasis; wounds can be classified as acute or chronic. Acute wounds heal in four sequential phases: hemostasis, inflammation, proliferation, and remodeling. Chronic wounds arise when this process fails, often due to prolonged inflammation. Existing treatments for chronic wounds are limited, and antibiotic resistance complicates infection control, highlighting the urgent need for new therapies. Biomaterials, particularly gelatin, have gained attention for their biomimetic properties, biocompatibility, and ability to promote healing. Gelatin’s ECM-like structure supports tissue metabolism, and it can be enriched with bioactive compounds to enhance tissue regeneration, collagen deposition, angiogenesis, and antimicrobial activity. This study evaluates the effectiveness of a 3D gelatin-based patch in vivo, using Hirudo verbana as a model. The patch, functionalized with chitosan and bioactive apatite nanoparticles, was implanted in injured leeches, with tissue samples collected at 72 h, 1 week, and 2 weeks. Scaffold integration, cell colonization, and healing effects were assessed through morphological, immunohistochemical, and ultrastructural analyses. The findings confirm H. verbana as a robust in vivo model for regenerative medicine and demonstrate the promising potential of gelatin-based patches. Full article

Galaxolide (HHCB), a synthetic polycyclic musk widely used as a fragrance ingredient in numerous personal care and household products, has raised increasing environmental concern due to its persistence, bioaccumulation potential, and widespread occurrence in aquatic environments. In this context, the need to establish a concrete ecotoxicological risk profile, defining both the toxicity levels and the mechanisms of action, is fundamental. For this reason, in the current study, we selected the freshwater leech Hirudo verbana as a suitable in vivo model to assess the HHCB ability in inducing inflammatory response and oxidative stress. By means of morphological, immunofluorescence, and molecular analyses, HHCB was shown not only to affect the leech innate immune response by modulating angiogenesis and macrophage-like cells recruitment, but also to promote the expression of enzymes involved in the antioxidant response, such as superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT). Overall, these findings indicate that HHCB could induce significant physiological alterations, with sub-lethal concentrations able to affect immune homeostasis. Furthermore, this study supports the use of alternative invertebrate models to better understand the possible harmful effects of emerging contaminants. Full article

Background: Poor or rapid growth velocity in early childhood can have negative long-term health consequences. Early identification of children at risk of growth problems facilitates timely intervention to change growth trajectories and health parameters, but barriers exist to routine screening in primary care. Methods: Experts from general practice, primary care nursing, pediatrics, dietetics, and academic research convened to develop a practical algorithm to support routine growth screening and intervention in children aged 1 to 5 years in primary care. Results: Using a single initial measurement of weight and height in conjunction with risk factor assessment, the algorithm presented here identifies children at risk of poor or rapid growth velocity and provides guidance for intervention and follow-up frameworks. Conclusions: This tool helps to define children in the community setting who are at risk of poor or rapid growth velocity and supports primary care providers in promoting healthy growth trajectories through timely intervention and continued routine growth monitoring. Full article

Leeches (Hirudinea) are ecologically important annelids that interact with a wide range of aquatic vertebrates, yet their diversity, distribution, and epidemiological relevance remain poorly documented in North Africa. Here, we provide a comprehensive synthesis of freshwater and marine leech species reported from the Maghreb (Algeria, Tunisia, and Morocco), based on an extensive review of the available literature. In total, 21 species belonging to 13 genera and four families (Glossiphoniidae, Erpobdellidae, Hirudinidae, and Piscicolidae) are documented, with updated information on their ecology, host associations, and geographic distribution. In addition to this regional checklist, we report the first confirmed case of Batracobdella algira heavy parasitism on the Berber toad (Sclerophrys mauritanica) in Algeria. A single adult toad was found heavily infested by multiple leeches (n = 17), some of which bore spermatophores attached near the reproductive opercula, suggesting possible in situ mating behavior on the host. The high infestation observed in this single specimen may constitute an outlier, requiring further sampling to assess the effect of leeches on the anuran population in the region. By integrating faunistic data with a novel field observation, this study highlights the overlooked leech biodiversity in the Maghreb and suggests their possible ecological and epidemiological significance. Our findings emphasize the need for further investigations into leech–host interactions, pathogen carriage, and their implications for amphibian conservation and One Health in North Africa. Full article

Background: Wrist osteomyelitis caused by Scedosporium apiospermum is exceedingly rare. Its indolent course and destructive potential may result in extensive bone loss and pose substantial diagnostic and therapeutic challenges. Methods: We report a case of chronic wrist osteomyelitis caused by Scedosporium apiospermum in a 68-year-old kidney–pancreas transplant recipient. Results: Following diagnosis, systemic antifungal therapy with voriconazole was initiated, and multiple surgical debridements were performed to achieve local disease control, resulting in a large defect of the carpus and distal forearm. Hand salvage was attempted using an osteocutaneous triple-barrel fibula flap. The postoperative course was complicated by congestion of the fibula skin island, which was managed with leech therapy. Subsequent infection with a multi-resistant Aeromonas spp. and Morganella morganii led to flap necrosis, ultimately requiring transradial forearm amputation. Conclusions: Destructive Scedosporium apiospermum osteomyelitis in immunocompromised patients is a major challenge for reconstructive surgeons. Interdisciplinary management is essential as mold eradication is only achievable through a combined surgical and antimicrobial approach. In advanced destructive osteomyelitis, the choice between limb salvage and amputation should be individualized, considering patient comorbidities, reconstructive risk, and patients’ preferences. This case highlights the importance of balancing careful indication and patient counseling in complex clinical scenarios. Full article

The bioactive compounds that are produced by leeches combine traditional and modern treatment since the saliva of the animal contains proteins and peptides with anticoagulant, anti-inflammatory, antimicrobial, antioxidant, and regenerative properties. In this review, their biochemical profile, mechanisms and clinical uses are considered with a special focus on the fact that they are utilized to combine traditional practices with the modern developments in biomedical approaches. Proteomic and transcriptomic research has recently found more than 100 bioactive molecules, such as hirudin, calin, eglins, bdellins and destabilase, which are related to the blood-feeding process and therapeutic processes. These compounds control blood clotting, control inflammatory mediators, block microbes and enhance wound healing and the development of new blood vessels. In clinical practice, leech therapy is common in the reconstruction and microsurgical practice to reduce venous congestion and enhance graft success. They are also shown to be useful in wound healing, cardiovascular health, musculoskeletal conditions and regenerative medicine, as well as emerging drug delivery systems of recombinant proteins and nanocarriers. Some of the challenges involve biological variation, infection or bleeding risks and stringent regulations on purity and standardization. Biotechnology has improved through other developments such as recombinant protein production, high-throughput omics, and nanotechnology, which will help resolve these problems, making them safe and scalable for clinical use. Altogether, leech bioactives are the prime examples of the sophisticated pharmacology of nature, which have the potential of being used as therapeutic agents in the future. The recent approach and incorporation in personalized medicine and bioengineering models reflect the leech’s capacity to address complicated illness and unmet healthcare requirements to reassert its significance in preventive medicine and recent biomedicine. Full article

Background/Objectives: We aimed to determine safe and immunogenic RSVpreF vaccine dose levels for further clinical development in 2–<18 year olds. Methods: The phase 1, age-descending, open-label Picasso trial evaluated different RSVpreF dose levels in respiratory syncytial virus (RSV)-seropositive 2–<5 year olds and 5–<18 year olds who were either healthy or had chronic medical conditions with increased RSV illness risk. Participants received a single dose of RSVpreF (60 µg or 120 µg dose level). The primary objective was to describe safety and tolerability at each dose level and age group, including frequencies of reactogenicity and adverse events (AEs). The secondary objective was to describe RSV neutralizing antibody responses at each dose level and age group 1 month after vaccination. Results: Overall, 127 participants received RSVpreF 60 µg (2–<5 year olds, n = 20; 5–<18 year olds, n = 35) or 120 µg (n = 24 and n = 48, respectively); 54% were male and 69% were White. Local reactions and systemic events were reported in 17–20% and 33–45% of 2–<5 year olds, respectively, and 49–56% and 52–60% of 5–<18 year olds; most were mild or moderate in severity. AEs were reported in 13–15% of 2–<5 year olds and 8–14% of 5–<18 year olds. No AEs leading to withdrawal or vaccine-related serious AEs were reported. RSV-A and RSV-B neutralizing titer geometric mean fold rises from before to 1 month after vaccination with RSVpreF 60 and 120 µg, which were 17.7–20.6 and 42.8–39.8, respectively, in 2–<5 year olds, and 19.0–23.5 and 20.3–20.3, respectively, in 5–<18 year olds. Conclusions: RSVpreF was safe, well tolerated, and elicited immune responses in RSV-seropositive 2–<18-year-old participants, supporting further clinical development in this pediatric population, including those with chronic conditions. Full article

Serotonin (5-HT) performs a wide range of neuromodulatory actions in the nervous system, including the regulation of the neurons that release it, by activation of several types of autoreceptors that modulate their electrical activity, as well as its own release. 5-HT neurons release serotonin in different manners from different subcellular structures, including the presynaptic terminals, the somatodendritic region and the axons. The different releasing structures of the same neurons have different types of autoreceptors, which exert differential auto-regulatory effects. Here we critically review the evidence of serotonergic autoregulation, both in mammals and in invertebrates, with particular emphasis on studies of serotonergic Retzius neurons of the leech, which have been a model for detailed studies of serotonin secretion from different neuronal structures. In these neurons serotonin produces different and even opposite effects on different releasing structures, such as the presynaptic terminals and the soma, through activation of different types of autoreceptors, thus increasing the specialization of the mechanisms that regulate exocytosis from each site. The differential autoregulation of serotonin release from different structures enables a single neuron to exert a variety of different functions in the nervous system. Full article