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Trichinella spiralis ( T. spiralis ) has been reported to induce inflammation, which can cause immune system dysregulation. Myeloid differentiation primary response gene 88 (MyD88) is implicated in inflammation signalling pathways. TJ-M2010-5 is a novel MyD88 inhibitor with remarkable protective effects against several diseases. However, the precise mechanism of TJ-M2010-5’s involvement in spleen impairment and inflammation in the early infection of T. spiralis has yet to be fully elucidated. This study analysed histological, inflammation, and macrophage polarisation of the early T. spiralis -infected mice treated with TJ-M2010-5. MyD88 promoter methylation results showed that the methylation levels in the 5 d group were lower compared to the control group ( P  < 0.05). Furthermore, the methylation led to an imbalance in anti-inflammatory regulation in the infected mice. After TJ-M2010-5 treatment, spleen impairment was reduced. Sequencing analysis showed that TJ-M2010-5 significantly up-regulated 9 and down-regulated 10 miRNAs compared with the 5 d group. A dual-luciferase reporter assay further revealed that miR-136-5p is involved in the TJ-M2010-5 treatment by targeting AKT3. In RAW264.7 cells, TJ-M2010-5 pre-treatment significantly reversed the M1 polarisation and inhibited nitric oxide (NO) production. LC–MS/MS results showed TJ-M2010-5 was hepatosplenic-targeted. In conclusion, the study demonstrates that TJ-M2010-5 could effectively alleviate spleen impairment and reduce inflammation in mice infected with T. spiralis in its early stages by blocking the activation of PI3K/miR-136-5p/AKT3.

One of the most significant lactic acid bacteria genera is Lactobacillus , which is known to generate compounds such as bacteriocins that can stop the growth of harmful bacteria. The current study investigated the protective and therapeutic effects of two novel probiotic strains, Lactobacillus brevis PQ214320, and Bacillus subtilis PQ198038, on parasitological, histopathological, and immunological responses in mice infected with Trichinella spiralis . A total of 120 mice were divided into six groups, including a positive control group (C) which was infected with Trichinella infection and not treated, mice treated orally with albendazole (ALB) at a dose of 5 mg/kg bw for 3 days after infection, and mice treated with probiotics (10 9 Colony-Forming Unit (CFU)/mL/animal, in 100 µL of Ringer’s solution) either pre- and post-infection with L. brevis PQ214320 (LP) or B. subtilis PQ198038 (BSP), or only post-infection with L. brevis PQ214320 (L) and B. subtilis PQ198038 (BS). Infection was induced by oral inoculation of 400 T. spiralis larvae. Parasite burden and, histopathological, and immune responses were assessed at 5 and 19 days post-infection. The results showed that the LP group had significantly reduced adult worm and muscle larval counts compared with the positive control group. In contrast, BSP reduced the parasite burden, but to a lesser extent. The immune response was characterized by elevated levels of IL 12 and IFN-γ in the LP group at 5 days -post-infection (dpi), indicating a strong Th1 response, which declined but remained significantly higher than in the control infected group at 19 dpi. Serum IgG responses were higher in the LP group at 19 dpi, suggesting that a more robust adaptive immune response was triggered by L. brevis . Pre- and post-treatment with B. subtilis PQ198038 and L. brevis PQ214320 significantly improved the histopathological abnormalities and collagen deposition in the small intestinal and diaphragm muscular tissues caused Trichinella infection and restored claudin 1 content in the same tissues. These findings suggest that L. brevis PQ214320 offers a stronger protective effect against T. spiralis infection, potentially through enhanced immune modulation and parasite reduction, whereas B. subtilis PQ198038 provides beneficial but less potent responses. This study highlights the potential of novel probiotics strains as adjunct protective agents and therapies against T. spiralis infection.

Helminth infections remain a significant global health and economic burden, and the growing emergence of resistance to frontline anthelmintic drugs such as albendazole and ivermectin underscores the urgent need for novel therapeutic strategies. Flavonoids, a diverse group of plant-derived polyphenolic compounds, have gained attention for their broad-spectrum biological activities, including potential antiparasitic properties. This study aimed to investigate the anthelmintic potential of orange-derived flavonoids using two complementary models: the free-living nematode Caenorhabditis elegans (wild-type, albendazole-resistant, and ivermectin-resistant strains) and the muscle-stage larvae of Trichinella spiralis as a representative parasitic nematode. Among the five flavonoids tested, quercetin exhibited the strongest anthelmintic activity across all C. elegans strains and against T. spiralis , while demonstrating minimal cytotoxicity in human cell lines, indicating a favorable safety profile. To investigate its potential mode of action, electron microscopy was employed to assess morphological changes, while a mass spectrometry-based metabolomics approach was used to examine molecular mechanisms in T. spiralis treated with quercetin. The results showed that quercetin did not induce detectable morphological alterations but significantly disrupted multiple key metabolic pathways, particularly those associated with energy production, lipid metabolism, and mitochondrial function, indicating a systemic metabolic disturbance. These findings offer new insights into the metabolic effects of orange-derived flavonoids and underscore quercetin as a promising lead candidate for anthelmintic development.

The present work aimed at studying the efficacy of mebendazole (MBZ) compared to artemisinin (ART) for the treatment of trichinellosis at various phases of infection. Seventy Swiss albino mice were orally infected by 300 Trichinella spiralis (T. spiralis) larvae. Mice were divided into infected untreated control group and infected groups treated with 50 mg kg−1 MBZ and 300 mg kg−1 ART for three and five consecutive days, respectively, at the enteral phase [2–4 days post infection (PI)], invasive phase (10–12 days PI) and encapsulated phase (28–30 days PI). All mice were sacrificed 35–42 days PI. MBZ and ART revealed a significant decrease in mean larval counts and increase of larval per cent reduction (LR %) when treatment was initiated during the enteral phase compared to the other phases. MBZ showed significantly higher LR % (99.7, 83.95 and 89.65%) than ART (80.58, 67.0 and 79.2%) when administered at the three infection phases. Histopathological study showed a decrease in the number of encysted larvae, their surrounding cellular infiltrates and increased regenerative muscles in all treated mice. In conclusion, ART possesses a substantial anthelmintic activity against T. spiralis infection in mice both at the enteral and encapsulated phases, yet, significantly lower than MBZ.

Trichinella spiralis is an important foodborne parasitic nematode that represents an enormous threat to the food safety of pork meat. The development of a preventive vaccine is valuable for the prevention and control of Trichinella infection in domestic pigs to ensure pork safety. Elastase is a trypsin-like serine protease that hydrolyzes the host’s diverse tissue components and participates in parasite penetration, and it might be a novel vaccine target molecule. The aim of this study was to assess the protective immunity produced by vaccination with a novel Trichinella spiralis elastase-1 (TsE) in a mouse model. The results demonstrate that subcutaneous vaccination of mice with rTsE elicited a systemic humoral response (high levels of serum IgG and subclass IgG1/IgG2a and IgA) and significant local enteral mucosal sIgA responses. Anti-rTsE IgG recognized the native TsE at the cuticle, stichosome of intestinal infective larvae and adult worm (AW), and intrauterine embryos of female AW. The rTsE vaccination also produced a systemic and local mixed Th1/Th2 response, as demonstrated by clear elevation levels of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4, IL-10) after spleen, mesenteric lymph node and Peyer’s patch cells from immunized mice were stimulated with rTsE. The immunized mice exhibited a 52.19% reduction in enteral AW and a 64.06% reduction in muscle larvae after challenge infection. The immune response triggered by rTsE vaccination protected enteral mucosa from larval intrusion, suppressed larval development and reduced female fecundity. The results indicate that TsE may represent a novel target molecule for anti- T. spiralis vaccines.

Trichinellosis is a meat-borne zoonosis of ubiquitous distribution. The severity is variable, and fatalities may occur. Immune-mediated inflammation plays an important role in the pathogenesis of the disease. Thus, safe and effective compounds with anti-inflammatory properties are needed. Our study was designed to evaluate the effects of fluvoxamine as an adjuvant to albendazole during the intestinal and migratory phases of trichinellosis. Therefore, Trichinella spiralis -infected mice were treated with either fluvoxamine, albendazole, or a combination of both drugs. Notably, the parasite burden was reduced in the intestines and muscles of fluvoxamine-treated mice compared to the infected control, denoting a detrimental effect of the drug against Trichinella spiralis . Moreover, in comparison with the infected control, there was a marked improvement in intestinal and muscle inflammation with the treatment, evidenced by the reduction in COX-2 and TNF-α and the decrement of inflammatory infiltrates in tissues. The expression of iNOS was also reduced in the muscles. Treatment with fluvoxamine alleviated the oxidative stress in the intestines and muscles with a reduction in malondialdehyde and H 2 O 2 and an increase in reduced glutathione levels. Finally, fluvoxamine moderated the immune response, as evidenced by the downregulation of the levels of IL-4 and IFN-γ and the increase of those of IL-10 in tissues. Characteristically, all these beneficial effects were maximal in mice receiving the combined treatment. In conclusion, fluvoxamine administration during the early phase of trichinellosis exhibited immunomodulatory and anti-inflammatory activities that potentiated the efficacy of albendazole. Therefore, fluvoxamine could be considered a useful adjuvant treatment in trichinellosis.

Twelve propolis samples from different parts of Libya were investigated for their phytochemical constituents. Ethanol extracts of the samples and some purified compounds were tested against Trypanosoma brucei, Plasmodium falciparum and against two helminth species, Trichinella spiralis and Caenorhabditis elegans, showing various degrees of activity. Fourteen compounds were isolated from the propolis samples, including a novel compound Taxifolin-3-acetyl-4′-methyl ether (4), a flavanonol derivative. The crude extracts showed moderate activity against T. spiralis and C. elegans, while the purified compounds had low activity against P. falciparum. Anti-trypanosomal activity (EC50 = 0.7 µg/mL) was exhibited by a fraction containing a cardol identified as bilobol (10) and this fraction had no effect on Human Foreskin Fibroblasts (HFF), even at 2.0 mg/mL, thus demonstrating excellent selectivity. A metabolomics study was used to explore the mechanism of action of the fraction and it revealed significant disturbances in trypanosomal phospholipid metabolism, especially the formation of choline phospholipids. We conclude that a potent and highly selective new trypanocide may be present in the fraction.

Background-Objective Trichinella spiralis drug development and control need an objective high throughput system to assess first stage larvae (L1) viability. YOLOv5 is an image recognition tool easily trained to count muscular first stage larvae (L1) and recognize morphological differences. Here we developed a semi-automated system based on YOLOv5 to capture photographs of 96 well microplates and use them for L1 count and morphological damage evaluation after experimental drug treatments. Material and methods Morphological properties were used to distinguish L1 from debris after pepsin muscle digestion and distinguish healthy (serpentine) or damaged (coiled) L1s after 72 h untreated or treated with albendazole or mebendazole cultures. An AxiDraw robotic arm with a smartphone was used to scan 96 well microplates and store photographs. Images of L1 were manually annotated, and augmented based on exposure, bounding, blur, noise, and mosaicism. Results A total of 1309 photographs were obtained that after L1 labeling and data augmentation gave 27478 images. The final dataset of 12571 healthy and 14907 affected L1s was used for training, testing, and validating in a ratio of 70/20/10 respectively. A correlation of 92% was found in a blinded comparison with bare-eye assessment by experienced technicians. Conclusion YOLOv5 is capable of accurately counting and distinguishing between healthy and affected L1s, thus improving the performance of the assessment of meat inspection and potential new drugs. Graphical Abstract

Background Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis , with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation. Methods The effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF). Results Sensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups. Conclusion Sensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response. Graphical Abstract

Trichinellosis, a resurgent zoonotic infestation, threatens public health due to recorded human outbreaks in various nations. The emergence of treatment resistance necessitates the exploration of efficient natural alternatives. Staphyloxanthin (STX), a membrane-associated secondary metabolite carotenoid pigment, underscores pro-oxidative traits, positioning it as a novel therapeutic candidate. Nanostructures demonstrated encouraging promise in overcoming low oral bioavailability, which could undermine the efficacy. Hence, the therapeutic outcome of STX-loaded niosomes was scrutinized both in vitro and in vivo. In this study, the prepared niosomal nanovesicles exhibited a spherical form in the nanoscale spectrum. Our in vitro findings demonstrated that STX markedly diminished larval viability, associated with excessive cuticular deformities, numerous notches, and membrane blebbing. The preclinical evaluation revealed that the oral delivery of STX-niosomes showed a superiority of therapeutic efficacy in mice compared to the reference drug. This was reflected by the eradicated adult worms, enhanced histopathological attributes, and reduced larval count. It is noteworthy that the biological findings revealed a significant reduction in the inflammatory expression of TNF-α surrounding trichina capsules. The relationship between STX and the parasite was elucidated, with the promising antiparasitic efficacy being further corroborated through in silico homology modelling and molecular docking approaches. The 3D-modelled target protein structures exhibited excellent quality factors and favourable Ramachandran plot statistics. Intriguingly, in silico docking results obviously revealed the potential affinity of STX to bind and block target protein receptors. In conclusion, our results suggested that STX pigment may serve as a promising pioneering alternative in the anthelmintic fight against trichinellosis.