Search Results (186)

This study aimed to determine the presence of relevant infectious and parasitic agents (IPAs) in managed honeybees from Central Italy and the Republic of Kosovo and Albania to assess the overall health status of local apiaries by determining the contamination levels and co-occurrence. Therefore, pathogens and parasites such as Paenibacillus larvae, Melissococcus plutonius, Vairimorpha apis, V. ceranae, the acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus variants DWV-A and DWV-B, and the parasitoid flies Megaselia scalaris and Senotainia tricuspis were detected by quantitative polymerase chain reaction (qPCR) and reverse transcriptase qPCR (RT-qPCR) in clinically healthy adult honeybees collected from 187 apiaries in the Abruzzo and Molise regions of Central Italy, 206 apiaries in the Republic of Kosovo in 2022 and 2023 and 18 apiaries in Albania in 2022. The percentages of positive samples and contamination for V. ceranae, P. larvae and DWV-B were significantly higher in the Republic of Kosovo and Albania, while the percentages of samples positive for M. plutonius, CBPV, DWV-A, and the parasitoid flies were higher in Central Italy. Additionally, P. larvae and some viruses showed significantly different occurrence rates between the two years in Italy and the Republic of Kosovo. The co-occurrence of IPAs also differed between the two geographic areas. Their varying distribution could depend on epidemiological dynamics, climatic factors, and management practices specific to each country, whose relative impact should be defined to guide targeted interventions to reduce honeybee mortality. Full article

This study evaluated hepatic pathological and phenotypic alterations, along with the inflammatory response, following sequential dengue virus (DENV) infection in Callithrix penicillata, a relevant model for human endemic scenarios. Twenty-six animals were initially infected subcutaneously with DENV-3. Thirteen were euthanized between 1 and 7 days post-infection (dpi) to assess the acute phase, and up to 60 dpi for the convalescent phase. The remaining animals received a secondary DENV-2 infection two months later. Liver samples underwent histopathological and immunohistochemical analysis. Viral antigens were identified in hepatocytes, Kupffer cells, and Councilman bodies. Observed liver changes included apoptosis, lytic necrosis, midzonal inflammation, Kupffer cell hyperplasia and hypertrophy, sinusoidal dilation, and hemosiderin deposition. Both primary and secondary infections increased activated macrophages, NK cells, S-100 protein, and B lymphocytes. Primary infection was associated with elevated CD4⁺ T cells, IFN-γ, TGF-β, IL-10, and Fas expression, whereas secondary infection induced higher IFN-γ, TNF-α, IL-8, Fas, and VCAM levels. These findings mirror hepatic alterations in severe human dengue cases and underscore the role of direct viral effects and immune dysregulation in liver injury. The results support C. penicillata as a suitable non-human primate model for studying DENV pathogenesis. Full article

Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein of the transferrin family that plays a central role in host defense, particularly in protection against infection and tissue injury. Abundantly present in colostrum, secretory fluids, and neutrophil granules, Lf exerts broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. These effects are mediated by iron sequestration, disruption of microbial membranes, inhibition of microbial adhesion, and interference with host–pathogen interactions. Beyond its antimicrobial functions, Lf regulates pro- and anti-inflammatory mediators and mitigates excessive inflammation. Additionally, Lf alleviates oxidative stress by scavenging reactive oxygen species and enhancing antioxidant enzyme activity. This review summarizes the current understanding of Lf’s biological functions, with a particular focus on its roles in microbial infections, immune modulation, oxidative stress regulation, and inflammation. These insights underscore the therapeutic promise of Lf as a natural, multifunctional agent for managing infectious and inflammatory diseases and lay the groundwork for its clinical application in immune-related disorders. Full article

Background: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) globally, linked to severe complications such as pelvic inflammatory disease and infertility. In the Brazilian Amazon, socioeconomic vulnerability and the absence of screening policies exacerbate risks, particularly among female sex workers (FSWs). Objective: This study aimed to determine the seroprevalence of anti-C. trachomatis IgG antibodies among FSWs in five municipalities of Pará State, Brazilian Amazon, and identify epidemiological factors associated with infection. Methods: A retrospective cross-sectional study (2005–2007) included 348 FSWs recruited via convenience sampling. Sociodemographic and behavioral data were collected through questionnaires, and blood samples were analyzed by ELISA for anti-C. trachomatis IgG. Statistical analyses included Fisher’s exact tests, odds ratios (ORs), and 95% confidence intervals (CIs), using SPSS 21.0. Results: Overall seroprevalence was 93.9% (327/348; 95% CI: 83.1–90%). Significant associations included a household income of 1–3 minimum wages (98.4%; p = 0.0002), sexual partners from the same region (98.8%; p = 0.0421), and age >42 years (96.3%). Most reported inconsistent condom use (43.7%), multiple monthly partners (54.6%), and illicit drug use (53.4%). Discussion: The extremely high seroprevalence reflects chronic C. trachomatis exposure, driven by socioeconomic deprivation and limited healthcare access. Comparisons with global data underscore the urgent need for screening policies, absent in Brazil for FSWs, and highlight the vulnerability of this population. Conclusions: The findings reveal an alarming burden of C. trachomatis exposure among Amazonian FSWs. Integrated strategies, including routine screening, sexual health education, and inclusion of FSWs in priority health programs, are critical to reduce transmission and associated complications. Full article

Serious enteric disease caused by seven species of Eimeira continues to cause significant economic damage to the poultry industry. E. acervulina is one of the most widespread strains in farms and has a significant impact on chicken weight loss. Currently, the use of anticoccidial agents to suppress the occurrence of coccidiosis in farms is considerably restricted due to public health and environmental pollution issues. It is important to understand the protective immunity of the host against Eimeria infections with regard to natural products that could be used as alternatives to anticoccidial agents. Berberine chloride is known for its various biological functions, including its anti-parasite activity. However, its impact on intestinal morphology and immune-related activity in broilers infected with Eimeria still remains unclear. The aim of this study is to evaluate the anticoccidial effects of a berberine-based diet in broilers infected with E. acervulina and to monitor the host immune phenomenon using transcriptomic analysis. Administration of berberine to chickens infected with E. acervulina significantly reduced fecal oocyst production and intestinal lesion scores, and increased duodenal villus height, indicating anticoccidial activity and positive effects on intestinal morphology. Transcriptomic analysis of chickens infected with E. acervulina generally observed the down-regulation of metabolism-related genes and the up-regulation of cell integrity-related genes at day 4 post-infection. At day 6 post-infection, an increase in immune-related genes and cellular-homeostasis-related genes was generally observed. Berberine-treated and E. acervulina-infected chickens showed cytokine-cytokine receptor interaction in the second term in a Kyoto Encyclopedia of Genes and Genomes pathway analysis at day 4 post-infection, but not in chickens infected with E. acervulina alone, suggesting host immune changes induced by berberine. These results suggest that berberine, which exhibits anticoccidial effects, may have therapeutic and/or prophylactic potential in protecting the host from infectious and economic-loss-causing diseases, such as Eimeria infection. Full article

Malaria is a parasitic infectious disease that is endemic in many tropical countries. Even though several effective antimalarial agents have been implemented, treatment failure still occurs, and malaria continues to cause neurological complications and death, particularly in severe or drug-resistant cases. Hence, novel therapeutic agents with distinct mechanisms of action, as well as alternative chemical compounds that can overcome resistance, are still needed to improve malaria therapy. This study aimed to investigate the antimalarial activities of Brucea javanica, a tropical plant extracts against Plasmodium falciparum, the major species associated with severe malaria. In this study, malaria parasites were treated with plant extracts using single and co-incubation methods, along with artesunate and chloroquine, and their inhibitory effect on parasite development was determined by microscopy. The results show that all tested doses of the extracts that effectively inhibited malaria parasites did not cause hemolysis of red blood cells (RBCs). The root extract (RE) and fruit extract (FE) inhibited parasite growth at IC₅₀ values of 0.41 ± 1.14 µg/mL and 0.26 ± 1.15 µg/mL, respectively. These plant extracts significantly interrupted malaria development at the ring stage, as presented by a reduction in the conversion rate to trophozoites and schizonts. The defective parasites treated with plant extracts were characterized by nuclear clumping, leading to pyknotic cell death. Moreover, RE and FW extracts elicited an additive effect with artesunate and chloroquine, significantly reducing IC₉₀ levels for the inhibition of parasite development. In conclusion, B. javanica extracts inhibited the asexual blood-stage development of malaria parasites. They distinctively show the additive effects of ATS and CRQ, elucidating their potential for further studies on novel formulas of antimalarial drug regimens. Full article

Trypanosoma cruzi is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of T. cruzi, with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5′-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in T. cruzi may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease. Full article

The increasing number of owned and stray dogs in large cities is becoming a pressing issue due to rising population densities, urban conditions, and poor control over animal reproduction. This situation poses serious epidemiological risks, as dogs can act as reservoirs and transmitters of infectious and parasitic diseases dangerous to humans. This study aimed to investigate the prevalence and carriage of infectious and parasitic diseases in stray dogs in the city of Uralsk as a factor of epidemiological risk. In 2024, 1213 stray dogs were captured from different city districts and examined at the veterinary clinic and laboratory of Zhangir Khan University. Biological samples (blood, urine, feces) from 10% of the animals were analyzed using molecular (PCR), serological (ELISA), and helminthological methods. Serological and molecular analyses revealed the widespread circulation of bacterial pathogens. Antibodies to additional bacterial agents, including Pasteurella multocida, Mycobacterium spp., Listeria monocytogenes, and Leptospira spp., were detected in the samples, indicating an unfavorable sanitary and epidemiological situation in the urban environment. An enzyme-linked immunosorbent assay (ELISA) identified antibodies against Toxocara canis in 50.9% of the dogs and against Echinococcus granulosus in 76.4%, reflecting both active and past infections. The polymerase chain reaction (PCR) results showed the presence of Brucella canis DNA in blood and urine samples, while antibodies to Brucella spp. were detected in 57.8% of the examined dogs, underscoring the significant zooanthroponotic importance of this pathogen and its potential threat to human health. Additionally, T. canis DNA was found in 39.2% of the samples and E. granulosus DNA in 16.6%. A helminthological examination using the Fülleborn method revealed a high rate of helminth infection: Ancylostoma caninum—35.3%, T. canis—32.3%, and Toxascaris leonina—29.4%. The obtained results highlight the significant role of stray dogs as epizootiological and epidemiological reservoirs of zooanthroponotic infections. This poses a serious threat to public health and necessitates the implementation of effective control and prevention measures for infectious and parasitic diseases within urban fauna. Full article

Background/Objectives: The increasing threat of antibiotic resistance and the declining efficiency of traditional drug discovery pipelines highlight the urgent need for novel drug targets and effective enzyme inhibitors against infectious diseases. Oligopeptidase B (OPB), a serine protease with trypsin-like specificity that processes low-molecular-weight peptides and oligopeptides, is present in bacteria and certain parasites but absent in mammals. This unique distribution makes OPB an attractive and selective target for antimicrobial drug development. Methods: Three-dimensional models of OPB from Serratia marcescens and Stenotrophomonas maltophilia, previously identified by our research group, were constructed via homology modeling using the best available OPB template from the RCSB Protein Data Bank. The S. marcescens OPB model was subjected to high-throughput virtual screening (HTVS) against the Natural Products Atlas (npatlas) database. Top-ranking compounds were further evaluated using Glide standard precision (SP) and extra precision (XP) docking protocols. Binding affinities were refined using molecular mechanics with generalized born and surface area (MM–GBSA) calculations. Molecular dynamics (MD) simulations assessed binding stability, while absorption distribution metabolism excretion and toxicity (ADMET) profiling evaluated drug-likeness and pharmacokinetic properties. Results: Ten natural product compounds demonstrated stronger binding affinities than antipain, a well-known oligopeptide-based protease inhibitor, as indicated by their more favorable MM–GBSA scores of −60.90 kcal/mol (S. marcescens) and −27.07 kcal/mol (S. maltophilia). Among these, dichrysobactin and validamycin E consistently exhibited favorable binding profiles across both OPB models. MD simulations confirmed the stability of their interactions with OPB active sites, maintaining favorable binding conformations throughout the simulation period. ADMET analysis suggested that while both compounds show promise, lead optimization is required to enhance their drug-like characteristics. Conclusions: This study identifies dichrysobactin and validamycin E as promising OPB inhibitors with potential antimicrobial activity. These findings support their further development as selective and potent agents against bacterial pathogens, including resistant strains, and underscore the need for experimental validation to confirm their efficacy and safety. Full article

Background/Objectives: Plant-derived secondary metabolites have long contributed to the discovery of novel therapeutic agents, especially in the treatment of parasitic and infectious diseases in developing countries. Metabolomics provides a systems-level approach to understanding plant biochemistry, enabling the discovery of secondary metabolites with pharmacological relevance. Taraxacum kok-saghyz (TKS), widely known for its rubber-producing capabilities, remains underexplored as a medicinal plant. Given the well-established therapeutic properties of Taraxacum officinale and the emerging pharmacological profiles of related species, this study investigates the metabolic composition of TKS roots and leaves to uncover bioactive compounds with antioxidant, anti-inflammatory, or hepatoprotective potential. Methods: Widely targeted metabolomics was conducted on 10-month-old field-grown Kultevar™ TKS plants using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Samples were hand-harvested and preserved on dry ice to maintain biochemical integrity. Metabolite identification and classification were performed using the MWDB and KEGG databases. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to evaluate metabolic variation between tissues. Results: A total of 1813 metabolites were identified, including flavonoids, alkaloids, lipids, amino acids, and phenolic compounds. Differential analysis revealed 964 significantly altered metabolites—609 downregulated and 355 upregulated in roots relative to leaves. Multivariate analysis confirmed clear tissue-specific metabolic profiles. KEGG pathway enrichment highlighted the involvement of flavonoid biosynthesis, amino acid metabolism, and lipid metabolism pathways, suggesting bioactive potential. This study presents the first comprehensive metabolic profile of TKS, highlighting its potential value beyond rubber production. The detection of numerous therapeutic secondary metabolites supports its promise as a pharmaceutical and nutraceutical resource. Further functional validation of identified compounds is warranted. Full article

This review summarizes the interactions between Trypanosoma cruzi, the etiologic agent of Chagas disease, and its vectors, the triatomines, and highlights open questions. Four important facts should be emphasized at the outset: (1) The development of T. cruzi strains and their interactions with the mammalian host and the insect vector vary greatly. (2) Only about 10 of over 150 triatomine species have been studied for their interactions with the protozoan parasite. (3) The use of laboratory strains of triatomines makes generalizations difficult, as maintenance conditions influence the interactions. (4) The intestinal microbiota is involved in the interactions, but the mutualistic symbionts, Actinomycetales, have so far only been identified in four species of triatomines. The effects of the vector on T. cruzi are reflected in a different colonization ability of T. cruzi in different triatomine species. In addition, the conditions in the intestine lead to strong multiplication in the posterior midgut and rectum, with infectious metacyclic trypomastigotes developing almost exclusively in the latter. Starvation and feeding of the vector induce the development of certain stages of T. cruzi. The negative effects of T. cruzi on the triatomines depend on the T. cruzi strain and are particularly evident when the triatomines are stressed. The intestinal immunity of the triatomines responds to ingested blood-stage trypomastigotes of some T. cruzi strains and affects many intestinal bacteria, but not all and not the mutualistic symbionts. The specific interaction between T. cruzi and the bacteria is evident after the knockdown of antimicrobial peptides: the number of non-symbiotic bacteria increases and the number of T. cruzi decreases. In long-term infections, the suppression of intestinal immunity is indicated by the growth of specific microbiota. Full article

In response to vaccination and/or infectious agents, the liver produces acute-phase proteins (APPs) driven by IL-6, which circulate in blood plasma as components of the humoral innate defense. This study investigates the liver of mice for possible effects of protective vaccination against primary blood-stage infections of Plasmodium chabaudi malaria on the expression of genes encoding APPs and IL-6 family members. Female Balb/c mice were vaccinated with a non-infectious vaccine prior to challenge with 10⁶ P. chabaudi-infected erythrocytes, resulting in about 80% survival of otherwise lethal infections. Gene expression microarrays were used to determine the relative transcript levels of genes in the livers of vaccinated and unvaccinated mice on days 0, 1, 4, 8, and 11 p.i. (post infectionem). Vaccination induced significant (p-value < 0.05) differences in the expression of malaria-responsive genes toward the end of crisis on day 11 p.i., when mice recovered from infections. These genes include Saa4, Apcs, Cp, and Crp, encoding APPs described to inhibitorily interact with parasitic blood stages; the genes F2, F7, F8, F9, F10, and F13b, and Plg, Plat, and Serpina5, encoding proteins balancing coagulation vs. fibrinolysis dysregulated by malaria, respectively; the genes Hc, C8a, C8b, C8g, and C9, encoding components of lytic complement membrane attack complex (MAC); and Cfh, Cfi, and C4bp, encoding complement-regulatory proteins. Vaccination accelerated, albeit differently, the malaria-induced activation of all three complement pathways, evidenced as higher transcript levels of C1qa, C1qb, C1qc, Fcna, Cfp, C3, Cfh, C8a, and C9 on day 4 p.i., C1ra, C1s, and C2 on day 1 p.i., and Serping1, encoding the multifunctional protease inhibitor C1INH, on day 0 p.i. Protective vaccination may also accelerate downregulation of the malaria-promoting lethality of IL-6 trans-signaling, which may contribute to an overall accelerated recovery of mice from otherwise lethal blood-stage malaria. Full article

The appendix, an integral part of the large intestine, may serve two purposes. First of all, it is a concentration of lymphoid tissue that resembles Peyer’s patches. It is also the main location in the body for the creation of immunoglobulin A (IgA), which is essential for controlling intestinal flora’s density and quality. Second, the appendix constitutes a special place for commensal bacteria in the body because of its location and form. Inflammation of the appendix, brought on by a variety of infectious agents, including bacteria, viruses, or parasites, is known as appendicitis. According to a number of studies, the consequences of appendectomies may be more subtle, and may relate to the emergence of heart disease, inflammatory bowel disease (IBD), and Parkinson’s disease (PD), among other unexpected illnesses. A poorer prognosis for recurrent Clostridium difficile infection is also predicted by the absence of an appendix. Appendectomies result in gut dysbiosis, which consequently causes different disease outcomes. In this review, we compared the compositional differences between the appendix and gut microbiome, the immunological role of appendix and appendix microbiome (AM), and discussed how appendectomy is linked to different disease consequences. Full article

Background/Objectives: The evaluation of the efficacy of COVID-19 vaccination in immunocompromised individuals, such as people living with HIV/AIDS (PLWH), still is of great global importance. The present study aimed to describe the presence of anti-SARS-CoV-2 IgG antibodies in PLWH vaccinated and unvaccinated against COVID-19 in the city of Belém, northern Brazil. Methods: A cross-sectional study involving 510 PLWH was conducted from December 2021 to May 2022. Participants answered a sociodemographic questionnaire and subsequently underwent an anti-SARS-CoV-2 enzyme immunoassay for the detection of IgG antibodies, as well as quantification of CD4+ T lymphocytes and HIV-1 plasma viral load. Results: Most participants were male (70%), aged 25–50 years (72%), single (71.4%), and low-income (50.4%). The prevalence of anti-SARS-CoV-2 IgG antibodies was 94.3% (481/510), with most vaccinated individuals having received at least two doses of a COVID-19 vaccine. An association was observed between antibody levels and the number of vaccine doses, CD4+ T lymphocyte count, CD4+/CD8+ T lymphocyte ratio, and HIV-1 viral load. Conclusions: PLWH developed high levels of antibodies against SARS-CoV-2 after receiving the vaccine, demonstrating that COVID-19 vaccination is of fundamental importance for the protection against severe COVID-19 in this specific group of immunocompromised individuals. Full article

Proteinopathies, characterized by the misfolding, aggregation, and deposition of proteins, are hallmarks of various neurodegenerative and systemic diseases. Increasingly, research has highlighted the role of protein misfolding in parasitic infections, unveiling intricate interactions between host and parasite that exacerbate disease pathology and contribute to chronic outcomes. The life cycles of parasitic protozoa, including Plasmodium, Toxoplasmosis, and Leishmania species, are complicated and involve frequent changes between host and vector environments. Their proteomes are severely stressed during these transitions, which calls for highly specialized protein quality control systems. In order to survive harsh intracellular conditions during infection, these parasites have been demonstrated to display unique adaptations in the unfolded protein response, a crucial pathway controlling endoplasmic reticulum stress. In addition to improving parasite survival, these adaptations affect host cell signaling and metabolism, which may jeopardize cellular homeostasis. By causing oxidative stress, persistent inflammation, and disturbance of cellular proteostasis, host–parasite interactions also contribute to proteinopathy. For instance, Plasmodium falciparum disrupts normal protein homeostasis and encourages the accumulation of misfolded proteins by influencing host redox systems involved in protein folding. In addition to interfering with host chaperone systems, the parasitic secretion of effector proteins exacerbates protein misfolding and aggregate formation. Autophagy, apoptosis regulation, organelle integrity, and other vital cellular processes are all disrupted by these pathological protein aggregates. Long-term misfolding and aggregation can cause irreversible tissue damage, which can worsen the clinical course of illnesses like visceral leishmaniasis, cerebral malaria, and toxoplasmosis. Treating parasite-induced proteinopathies is a potentially fruitful area of therapy. According to recent research, autophagy modulators, proteasome enhancers, and small-molecule chaperones may be repurposed to lessen these effects. Pharmacological agents that target the UPR, for example, have demonstrated the ability to decrease parasite survival while also reestablishing host protein homeostasis. Targeting the proteins secreted by parasites that disrupt host proteostasis may also offer a novel way to stop tissue damage caused by proteinopathies. In conclusion, the intersection of protein misfolding and parasitic infections represents a rapidly advancing field of research. Dissecting the molecular pathways underpinning these processes offers unprecedented opportunities for developing innovative therapies. These insights could not only transform the management of parasitic diseases but also contribute to a broader understanding of proteinopathies in infectious and non-infectious diseases alike. Full article