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PLoS Pathogens May 2024The common liver fluke (Fasciola hepatica) causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a...
The common liver fluke (Fasciola hepatica) causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a shortfall in the drugs that are effective against both the adult and juvenile life stages within the mammalian host, such that new drug targets are needed. Over the last decade the stem cells of parasitic flatworms have emerged as reservoirs of putative novel targets due to their role in development and homeostasis, including at host-parasite interfaces. Here, we investigate and characterise the proliferating cells that underpin development in F. hepatica. We provide evidence that these cells are capable of self-renewal, differentiation, and are sensitive to ionising radiation- all attributes of neoblasts in other flatworms. Changes in cell proliferation were also noted during the early stages of in vitro juvenile growth/development (around four to seven days post excystment), which coincided with a marked reduction in the nuclear area of proliferating cells. Furthermore, we generated transcriptomes from worms following irradiation-based ablation of neoblasts, identifying 124 significantly downregulated transcripts, including known stem cell markers such as fgfrA and plk1. Sixty-eight of these had homologues associated with neoblast-like cells in Schistosoma mansoni. Finally, RNA interference mediated knockdown of histone h2b (a marker of proliferating cells), ablated neoblast-like cells and impaired worm development in vitro. In summary, this work demonstrates that the proliferating cells of F. hepatica are equivalent to neoblasts of other flatworm species and demonstrate that they may serve as attractive targets for novel anthelmintics.
Topics: Animals; Fasciola hepatica; Stem Cells; Fascioliasis; Cell Proliferation; Cell Differentiation
PubMed: 38805551
DOI: 10.1371/journal.ppat.1011903 -
Journal of Neuroinflammation May 2024Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders... (Review)
Review
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.
Topics: Brain Injuries, Traumatic; Humans; Animals; Meninges; Neuroinflammatory Diseases; Neuroimmunomodulation
PubMed: 38802931
DOI: 10.1186/s12974-024-03122-7 -
Scientific Reports May 2024The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and...
The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and potential therapeutic targets. However, the relationship between these two diseases remains unclear and effective medical treatments are still lacking. Through the bioinformatics analysis in this study, 116 shared differentially expressed genes (SDEGs) were identified between IBD and NASH datasets. GO and KEGG pathway analyses revealed significant involvement of SDEGs in apoptotic processes, cell death, defense response, cytokine and chemokine activity, and signaling pathways. Furthermore, weighted gene co-expression network analysis (WGCNA) identified five shared signature genes associated specifically with IBD and NASH, they were CXCL9, GIMAP2, ADAMTS5, GRAP, and PRF1. These five genes represented potential diagnostic biomarkers for distinguishing patients with diseases from healthy individuals by using two classifier algorithms and were positively related to autophagy, ferroptosis, angiogenesis, and immune checkpoint factors in the two diseases. Additionally, single-cell analysis of IBD and NASH samples highlighted the expression of regulatory genes in various immune cell subtypes, emphasizing their significance in disease pathogenesis. Our work elucidated the shared signature genes and regulatory mechanisms of IBD and NASH, which could provide new potential therapies for patients with IBD and NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Inflammatory Bowel Diseases; Computational Biology; Gene Regulatory Networks; Gene Expression Profiling; Chemokine CXCL9; Biomarkers; Transcriptome; Gene Expression Regulation
PubMed: 38802459
DOI: 10.1038/s41598-024-62310-w -
Nature Communications May 2024Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and...
Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.
Topics: Humans; Male; Virus Shedding; Antibodies, Viral; Prospective Studies; Adult; Monkeypox virus; Mpox (monkeypox); Saliva; HIV Infections; Antibodies, Neutralizing; Middle Aged; Longitudinal Studies; DNA, Viral; Oropharynx; Coinfection; Viral Load; Fomites
PubMed: 38802350
DOI: 10.1038/s41467-024-48754-8 -
Parasite Epidemiology and Control May 2024Cystic echinococcosis (CE) is a major medical and veterinary concern in the world. It is one of the significant diseases in livestock farming communities managed under...
Epidemiological study on bovine cystic echinococcosis: Abattoir survey, cyst characterization and its economic impact at Mekaneyesuse municipality abattoir, Northwest Ethiopia.
Cystic echinococcosis (CE) is a major medical and veterinary concern in the world. It is one of the significant diseases in livestock farming communities managed under extensive grazing system like Ethiopia. Domestic intermediate hosts are an important reservoir for the disease spread. A cross-sectional study was conducted to determine the occurrence and economic losses associated with CE in cattle slaughtered at Mekaneyesuse Municipality abattoir, South Gondor zone of Amhara Region, North West Ethiopia. Ante-mortem inspection, postmortem examinations of organs, hydatid cyst characterization and financial loss estimations were conducted. The study was conducted on 384 cattle. The involvement of different organs was as follows: lungs (46.09%), liver (45.22%), heart (6.09%), and kidneys (2.6%). Out of the total of 115 cysts observed, small cysts constituted 57.39%, medium-sized were 34.78%, and large cysts accounted for 7.83%. Of these 115 cysts, 53.9% were fertile which included both viable (29%) and non-viable (71%) cysts. Furthermore, 46.1% cysts were non fertile, 62.3% were sterile and 37.7% were calcified. Based on the origin of animal, the prevalence of hydatid cysts was recorded to be 31.25%, 24%, 22.05% and 14.25% in Tachgayent, Semada, Andabet and Estie district, respectively. Higher cyst occurrence was observed in animals with poor body condition (51.56%) followed by medium (13.7%) and good body condition scores (8.25%). The total annual economic loss due to the direct condemnation of organs and indirect losses were estimated to be 851,252.68 ETB ($16,061.06). This study revealed that CE is economically important disease at Mekaneyesuse, South Gondar Zone, Amhara Region, Northwest Ethiopia. A more comprehensive investigation is required on prevalence and genotyping of cysts is important also to identify and estimate the relative contribution of each species or genotype to the disease in this area. Moreover, efforts to enhance public awareness in the area should also be pursued.
PubMed: 38800636
DOI: 10.1016/j.parepi.2024.e00355 -
MedRxiv : the Preprint Server For... May 2024Chickens are an important source of animal protein, nutrition, and income in many low- and middle-income countries (LMICs). They are also a major reservoir of...
BACKGROUND
Chickens are an important source of animal protein, nutrition, and income in many low- and middle-income countries (LMICs). They are also a major reservoir of enteropathogens that contribute to the burden of illnesses among children. Food systems present a risk for transmission of enteropathogens from poultry to humans, but there is a lack of population-level data on the pattern of purchase, ownership, and consumption of live chickens and their products in LMICs to better characterize that risk.
METHODS
To assess chicken purchase, ownership, and consumption practices, we conducted a population-based survey using a structured questionnaire in Maputo, Mozambique in 2021. Multi-stage cluster sampling was used to obtain a representative sample of households in our study area. To minimize sampling bias and ensure a representative sample, we applied survey weighting using district-level population data and estimated weighted population-level values.
RESULTS
Heads of 570 households in Maputo completed our survey. Approximately half of these households purchased broiler chicken meat (weighted percentage of households: 44.8%) and eggs (46.5%) in the previous week of the survey date, while indigenous chicken meat was less popular (1,950, 1.1%). The most common source of chicken products was corner stores (i.e., small convenience shops on streets), followed by wet markets. Live chickens were raised by 15.6% of households, and chicken feces were observed on the floor or ground at the majority of these households during house visits.
DISCUSSION
Our findings suggest that poultry provides a major source of animal protein in this setting. With the predicted growth of poultry farming in LMICs in the coming decades, ensuring food safety at the primary sources of chicken products (corner stores and wet markets) in urban areas will be critical to mitigate health risks.
PubMed: 38798325
DOI: 10.1101/2024.05.14.24307337 -
SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies.Viruses Apr 2024Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized... (Review)
Review
Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns has revoked all authorized immunotherapeutics. Rapid viral evolution has also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative to understand how Omicron evolves into different subvariants and causes immune escape as this could help reevaluate the current intervention strategies mostly implemented in the clinics as emergency measures to counter the pandemic and, importantly, develop new solutions. Here, we provide a review focusing on the major events of Omicron viral evolution, including the features of spike mutation that lead to immune evasion against monoclonal antibody (mAb) therapy and vaccination, and suggest alternative durable options such as the ACE2-based experimental therapies superior to mAbs to address this unprecedented evolution of Omicron virus. In addition, this type of unique ACE2-based virus-trapping molecules can counter all zoonotic SARS coronaviruses, either from unknown animal hosts or from established wild-life reservoirs of SARS-CoV-2, and even seasonal alpha coronavirus NL63 that depends on human ACE2 for infection.
Topics: SARS-CoV-2; Humans; Immune Evasion; COVID-19; Spike Glycoprotein, Coronavirus; Angiotensin-Converting Enzyme 2; Animals; Evolution, Molecular; Antibodies, Monoclonal; Mutation; COVID-19 Vaccines; Antibodies, Viral
PubMed: 38793580
DOI: 10.3390/v16050697 -
Antioxidants (Basel, Switzerland) May 2024Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, stands out as a promising edible plant. In this study, young and old leaves...
Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, stands out as a promising edible plant. In this study, young and old leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver's drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia's potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD.
PubMed: 38790701
DOI: 10.3390/antiox13050596 -
Journal of Hazardous Materials Jul 2024Wildlife is known to serve as carriers and sources of antimicrobial resistance (AMR). Due to their unrestricted movements and behaviors, they can spread antimicrobial...
Wildlife is known to serve as carriers and sources of antimicrobial resistance (AMR). Due to their unrestricted movements and behaviors, they can spread antimicrobial resistant bacteria among livestock, humans, and the environment, thereby accelerating the dissemination of AMR. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is one of major concerns threatening human and animal health, yet transmission mechanisms at the wildlife-livestock interface are not well understood. Here, we investigated the mechanisms of ESBL-producing bacteria spreading across various hosts, including cattle, feral swine, and coyotes in the same habitat range, as well as from environmental samples over a two-year period. We report a notable prevalence and clonal dissemination of ESBL-producing E. coli in feral swine and coyotes, suggesting their persistence and adaptation within wildlife hosts. In addition, in silico studies showed that horizontal gene transfer, mediated by conjugative plasmids and insertion sequences elements, may play a key role in spreading the ESBL genes among these bacteria. Furthermore, the shared gut resistome of cattle and feral swine suggests the dissemination of antibiotic resistance genes at the wildlife-livestock interface. Taken together, our results suggest that feral swine may serve as a reservoir of ESBL-producing E. coli.
Topics: Animals; Escherichia coli; beta-Lactamases; Animals, Wild; Swine; Disease Reservoirs; Cattle; Gene Transfer, Horizontal; Livestock; Drug Resistance, Bacterial; Escherichia coli Infections
PubMed: 38788585
DOI: 10.1016/j.jhazmat.2024.134694 -
Preventive Veterinary Medicine Jul 2024Wild lagomorphs play a key epidemiological role as reservoirs of Leishmania infantum, causative agent of the largest outbreak of human leishmaniosis in Europe to date. A...
Wild lagomorphs play a key epidemiological role as reservoirs of Leishmania infantum, causative agent of the largest outbreak of human leishmaniosis in Europe to date. A large-scale survey study was conducted on wild rabbit (Oryctolagus cuniculus) and Iberian hare (Lepus granatensis) populations in Spanish Mediterranean ecosystems to evaluate the exposure of L. infantum and investigate potential risk factors associated with exposure to this zoonotic parasite. Between 2018 and 2021, a total of 631 wild lagomorphs (471 wild rabbits and 160 Iberian hares) were collected in Andalusia (southern Spain) and tested for antibodies against L. infantum using the indirect fluorescent antibody test (IFAT). Spleen samples from 563 of the wild lagomorphs sampled (441 wild rabbits and 122 Iberian hares) were also evaluated by real-time quantitative PCR (qPCR) for detection of Leishmania kDNA. Exposure to L. infantum (positive by IFAT and/or qPCR) was detected in 56.4 % (356/631; 95 %CI: 52.3-60.3) of the lagomorphs analyzed. Anti-Leishmania antibodies were found in 12.8 % (81/631; 95 %CI: 10.2-15.5) of the animals, and L. infantum kDNA was detected in 59.0 % (332/563; 95 %CI: 54.9-63.0) of the spleen samples tested. Phylogenetic analysis revealed high homology (99.9-100 %) between L. infantum sequences obtained and strains previously isolated from humans in Spain. While apparent seroprevalence was significantly higher in Iberian hares (19.4 %; 95 %CI: 13.3-25.5) compared to wild rabbits (10.6 %; 95 %CI: 7.9-13.4), no significant differences in prevalence were found between wild rabbits (61.0 %; 95 %CI: 56.5-65.6) and Iberian hares (51.6 %; 95 %CI: 42.8-60.5). At least one positive animal was found on 64.8 % (70/108) of the hunting grounds sampled, and a high-risk spatial cluster (P < 0.001) was also identified in central Andalusia. The multivariable analysis identified bioclimatic level (meso-Mediterranean climate) and the presence of goats on hunting grounds as risk factors potentially associated with L. infantum exposure in wild lagomorphs. This study shows high, widespread exposure, but heterogeneous distribution of L. infantum in wild lagomorph populations in Mediterranean ecosystems in southern Spain. The results point to the need to promote integrated surveillance programs for the detection of Leishmania spp. in wild lagomorphs in order to establish effective control measures against human leishmaniosis under a One Health approach.
Topics: Animals; Leishmania infantum; Spain; Leishmaniasis, Visceral; Animals, Wild; Hares; Rabbits; Prevalence; Epidemiological Monitoring; Ecosystem; Female; Male; Disease Reservoirs; Antibodies, Protozoan; Seroepidemiologic Studies; Lagomorpha
PubMed: 38788301
DOI: 10.1016/j.prevetmed.2024.106231