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Gut Microbes 2024Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay...
Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundworm , and altered the host tissue transcriptome at the site of infection with the large intestinal whipworm , with a notable enhancement of type-1 inflammatory and interferon-driven gene pathways. In the absence of infection, PAC intake promoted the expansion of within the gut microbiota, increased fecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-γ-valerolactones in the cecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected with , suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the cecum dwelling ), and infection may abrogate the beneficial effects of health-promoting phytochemicals.
Topics: Animals; Gastrointestinal Microbiome; Mice; Polyphenols; Trichuris; Trichuriasis; Nematospiroides dubius; Proanthocyanidins; Mice, Inbred C57BL; Strongylida Infections; Female; Bacteria; Feces
PubMed: 38944838
DOI: 10.1080/19490976.2024.2370917 -
Nature Communications Jun 2024Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4 T cell...
Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4 T cell subsets remain unresolved. Here, we examine antigen-experienced CD4 T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic T cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with T/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4 T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4 T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.
Topics: Animals; Malaria; CD4-Positive T-Lymphocytes; Mice; Reinfection; Th1 Cells; Mice, Inbred C57BL; Spleen; Receptors, Antigen, T-Cell; Mice, Transgenic; Female; Immunologic Memory
PubMed: 38944658
DOI: 10.1038/s41467-024-49879-6 -
Vaccine Jun 2024Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who...
Suspected allergic reactions after mRNA COVID-19 vaccination withheld multiple individuals from getting fully vaccinated during the pandemic. We vaccinated adults who had experienced possible allergic symptoms after their first intramuscular dose of a COVID-19 mRNA vaccine with a 1/5th fractional intradermal test dose of the mRNA-1273 (Moderna) COVID-19 vaccine. No anaphylactic reactions were observed after intradermal vaccination (n = 56). Serum anti-S1 IgG concentrations were measured using a bead-based multiplex assay four weeks after vaccinations. Antibody concentrations were compared with a previously collected nationwide cohort that had received two intramuscular doses of mRNA-1273. Antibody responses in all subjects tested (n = 47) were comparable to standard of care intramuscular dosing. Fractional intradermal dosing of mRNA COVID-19 vaccines may provide a pragmatic solution that is safe, time efficient compared to skin prick testing, dose sparing and immunogenic in individuals with suspected vaccine allergy.
PubMed: 38944578
DOI: 10.1016/j.vaccine.2024.06.060 -
Acta Tropica Jun 2024Colpodella species are close relatives of Apicomplexan protozoa. Although most species of this genus are free-living organisms that feed on other protists and algae,...
Colpodella species are close relatives of Apicomplexan protozoa. Although most species of this genus are free-living organisms that feed on other protists and algae, reports indicate their occurence in ticks and human patients, including an individual with a history of tick bite manifesting neurological symptoms. During an investigation of tick-borne pathogens (TBPs) in blood samples of cattle, goats, and in ticks collected on them, Colpodella sp. DNA was detected in a Rhipicephalus bursa tick collected from cattle, while of Theileria sergenti/buffeli/orientalis, Babesia bigemina, Sarcocystis cruzi, Babesia spp., and Rickettsia spp. were molecularly detected in cattle, goats, and ticks in southern Italy. Data herein reported highlight the unprecedented presence of Colpodella sp. in ticks in Italy, raising concern due to the potential pathogenic role of this less known protozoan. This finding advocates for performing routine epidemiological surveys to monitor potential emerging vector-borne pathogens.
PubMed: 38944407
DOI: 10.1016/j.actatropica.2024.107306 -
Molekuliarnaia Biologiia 2024CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification...
CRISPR/Cas systems are perspective molecular tools for targeted manipulation with genetic materials, such as gene editing, regulation of gene transcription, modification of epigenome etc. While CRISPR/Cas systems proved to be highly effective for correcting genetic disorders and treating infectious diseases and cancers in experimental settings, clinical translation of these results is hampered by the lack of efficient CRISPR/Cas delivery vehicles. Modern synthetic nanovehicles based on organic and inorganic polymers have many disadvantages, including toxicity issues, the lack of targeted delivery, and complex and expensive production pipelines. In turn, exosomes are secreted biological nanoparticles that exhibit high biocompatibility, physico-chemical stability, and the ability to cross biological barriers. Early clinical trials found no toxicity associated with exosome injections. In the recent years, exosomes have been considered as perspective delivery vehicles for CRISPR/Cas systems in vivo. The aim of this study was to analyze the efficacy of CRISPR/Cas stochastic packaging into exosomes for several human cell lines. Here, we show that Cas9 protein is effectively localized into the compartment of intracellular exosome biogenesis, but stochastic packaging of Cas9 into exosomes turns to be very low (~1%). As such, stochastic packaging of Cas9 protein is very ineffective and cannot be used for gene editing purposes. Developing novel tools and technologies for loading CRISPR/Cas systems into exosomes is needed.
Topics: Exosomes; Humans; CRISPR-Cas Systems; Gene Editing; CRISPR-Associated Protein 9
PubMed: 38943588
DOI: No ID Found -
Iranian Journal of Immunology : IJI Jun 2024Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease...
Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for β-thalassemia major in children. However, it often induces graft-versus-host-disease (GVHD), which is associated with complications. In the present study, we used cyclophosphamide (Cy) to treat a thalassemia patient post-HSCT to reduce the adverse effects of GVHD. We monitored the numbers and phenotype of granulocytes. In this case study, an 11-year-old female patient, diagnosed with β-thalassemia major (Pesaro class II), was treated with Cy before and after HSCT with mobilized CD34+ cells. Both the relative and absolute granulocyte counts, as well as CD33+CD11b+ cell counts, increased significantly after HSCT until day 56. However, they suddenly began to decrease after day 56, accompanied by severe diarrhea, skin rash, and a decrease in bilirubin levels compared to day -12. Furthermore, compared to day -12, IL-22 levels increased until day 56, and then decreased, while IDO levels continued to rise after day 56. Our data suggest the potential use of IL-22 and IDO as biomarkers for GVHD assessment. It also indicates that Cy promotes HSCT reconstitution by increasing CD33+CD11b+ cells, which may play a crucial role in reducing GVHD risks. However, further studies are needed to elucidate the mechanism behind GVHD recurrence.
PubMed: 38943529
DOI: 10.22034/iji.2024.101584.2752 -
Journal of Animal Science Jun 2024Rations containing different rates of the mixed fodder beet tops-wheat straw silage (BS), instead of corn silage (CS), were given to 30 mid-lactation Holstein cows (all...
Rations containing different rates of the mixed fodder beet tops-wheat straw silage (BS), instead of corn silage (CS), were given to 30 mid-lactation Holstein cows (all in parity 2) to measure the effects on feed consumption, milk production efficiency, milk chemistry, urinary purine-derivatives (PD), blood chemistry, antioxidant levels, and in vitro methane (CH4) emission. The BS was prepared by mixing the fodder beet tops with wheat straw at a ratio of 9:1 based on fresh weight. The experimental design was completely randomized (one 28-d period with 21-d adaptation) using 30 cows (10 animals/treatment) and 3 treatments. The treatments were 1) a diet containing CS only (25 g/100 g DM) (CSD), 2) a diet containing 50% CS (12.5 g/100 g DM) and 50% BS (12.5 g/100 g DM) (CBSD), and 3) diet containing BS only (25 g/100 g DM) (BSD). Each animal (as an experimental unit) was housed individually in the tie stall and had ad libitum access to its diet. Dietary replacing 50% of CS with BS showed no significant differences in milk production, fat-corrected milk, fat and protein yields, feed efficiency, and apparent digestibility, however, these variables were less (P < 0.05) in the cows fed with BSD. Cows fed on BSD had less intakes of DM, organic matter, crude protein, and neutral detergent fiber but greater oxalic acid intake and blood urea-N, as compared to the other cows. Milk percentages of fat, protein, lactose, urea N, blood serum glucose, triglyceride, cholesterol, total protein, albumin, globulin, Ca, and P, as well as in vitro ruminal pH, were not affected by the diets. Saturated fatty acids concentration was less and monounsaturated FA and polyunsaturated FA (PUFA) was greater in the milk of cows receiving CBSD, compared to the other groups. The inclusion of both BS rates in the diet decreased the in vitro gas production, protozoa number, and CH4 emission in comparison to the control. Cows fed BSD had decreased levels of urinary allantoin, PD excreted or absorbed, and estimated microbial-N synthesis than the control and CBSD-fed groups. The milk and blood total antioxidant capacity (TAC) of the animals fed CBSD was the maximum among the cows. Overall, under the current experimental conditions, replacing 50% of dietary CS with BS did not affect milk production, but increased milk PUFA, as well as blood and milk TAC, and decreased in vitro CH4 emission, so it's feeding to lactating Holstein cows is recommended.
PubMed: 38943457
DOI: 10.1093/jas/skae179 -
Journal of Fish Diseases Jun 2024Alternatives to conventional chemical treatments for parasitic diseases in fish are needed. Microalgal-sourced fatty acid ethyl esters (FAEEs) have shown an...
Alternatives to conventional chemical treatments for parasitic diseases in fish are needed. Microalgal-sourced fatty acid ethyl esters (FAEEs) have shown an antiparasitic effect against Gyrodactylus turnbulli infection in guppies. Here, we tested a range of commercial FAEEs of various carbon chain lengths and unsaturation levels against two fish parasites. Guppies and barramundi infected with G. turnbulli and Trichodina sp., respectively, were used. The most effective FAEE, after excluding those toxic to fish, was ethyl laurate (12:0). For both parasites, the LD50 was 18.75 μM within 250 min of incubation. Ethyl eicosapentaenoate (20:5n3) was the next most effective FAEE against G. turnbulli, and dihomo-γ-linolenic acid ethyl ester (20:3n6) and ethyl α-linolenate (18:3n3) were the next most effective against Trichodina sp. In addition, FAEEs prepared from the microalga Phaeodactylum tricornutum residue, after fucoxanthin extraction, were examined against Trichodina sp. infection in barramundi for the first time. LD85 and LD100 was achieved at 2.5 and 5 μL mL of the FAEE preparation, respectively. In vivo, immersion of infected barramundi in 1.25 μL mL of this preparation for 24 h reduced infection prevalence from 100% to 53% and was non-toxic to fish.
PubMed: 38943443
DOI: 10.1111/jfd.13991 -
Successful treatment of fulminant and recurrent lymphocytic myocarditis with calcineurin inhibitors.ESC Heart Failure Jun 2024Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM...
Lymphocytic myocarditis (LM) is primarily triggered by various factors including viral infections and subsequent immune responses. While rare, some patients with LM experience recurrence with a life-threatening fulminant form. Although combining steroids and immunosuppressants, such as azathioprine and mycophenolate mofetil, has demonstrated favourable outcomes in patients with LM, their efficacy is limited to the chronic phase. Indeed, various immunosuppressants have been used for LM with fulminant manifestation; however, their evidence remains lacking. In our case series, two patients with LM experienced fulminant relapses during steroid tapering, and another presented persistent cardiac enzymes elevation despite steroid therapies. Consequently, we initiated calcineurin inhibitors alongside steroids, resulting in well-controlled clinical courses without further recurrence of LM and significant adverse effects. Our cases suggest calcineurin inhibitors as therapeutic options for managing steroid-resistant LM with fulminant relapse.
PubMed: 38943229
DOI: 10.1002/ehf2.14896 -
Parasites & Vectors Jun 2024African swine fever (ASF) is a highly contagious and severe haemorrhagic disease of Suidae, with mortalities that approach 100 percent. Several studies suggested the...
BACKGROUND
African swine fever (ASF) is a highly contagious and severe haemorrhagic disease of Suidae, with mortalities that approach 100 percent. Several studies suggested the potential implication of non-biting dipterans in the spread of ASFV in pig farms due to the identification of the ASFV DNA. However, to our knowledge, no study has evaluated the viral DNA load in non-biting dipterans collected in outbreak farms and no risk factors have been analysed. In this context, our study aimed to analyse the risk factors associated with the presence of non-biting dipterans collected from ASF outbreaks in relation to the presence and load of viral DNA.
METHODS
Backyard farms (BF), type A farms (TAF), and commercial farms (CF), were targeted for sampling in 2020. In 2021, no BF were sampled. Each farm was sampled only once. The identification of the collected flies to family, genus, or species level was performed based on morphological characteristics using specific keys and descriptions. Pools were made prior to DNA extraction. All extracted DNA was tested for the presence of the ASFV using a real-time PCR protocol. For this study, we considered every sample with a CT value of 40 as positive. The statistical analysis was performed using Epi Info 7 software (CDC, USA).
RESULTS
All collected non-biting flies belonged to five families: Calliphoridae, Sarcophagidae, Fanniidae, Drosophilidae, and Muscidae. Of the 361 pools, 201 were positive for the presence of ASFV DNA. The obtained CT values of the positive samples ranged from 21.54 to 39.63, with a median value of 33.59 and a mean value of 33.56. Significantly lower CT values (corresponding to higher viral DNA load) were obtained in Sarcophagidae, with a mean value of 32.56; a significantly higher number of positive pools were noticed in August, mean value = 33.12.
CONCLUSIONS
Our study brings compelling evidence of the presence of the most common synanthropic flies near domestic pig farms carrying ASFV DNA, highlighting the importance of strengthening the biosecurity measures and protocols for prevention of the insect life cycle and distribution.
Topics: Animals; African Swine Fever Virus; African Swine Fever; Swine; Disease Outbreaks; Farms; DNA, Viral; Romania; Diptera; Insect Vectors
PubMed: 38943218
DOI: 10.1186/s13071-024-06346-x