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Extracellular Vesicle Jun 2024Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect...
Extracellular vesicles (EVs) are membrane-bound vesicles released into the extracellular milieu from various cell types including host cells and pathogens that infect them. As carriers of nucleic acids, proteins, lipids, metabolites, and virulence factors, EVs act as delivery vehicles for intercellular communication and quorum sensing. Innate immune cells have the capacity to intercept, internalize, and interpret 'messages' contained within these EVs. This review categorizes the ability of EVs secreted by bacterial, parasitic, and fungal pathogens to trigger both pro- and anti-inflammatory innate immune responses in the host. Understanding molecular pathways and inflammatory responses activated in innate immune cells upon pathogen-derived EV stimulation is critical to gain insight into potential therapeutics and combat these infectious diseases.
PubMed: 38939756
DOI: 10.1016/j.vesic.2024.100043 -
Current Tropical Medicine Reports Dec 2023Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne parasitic neglected tropical disease (NTD) endemic in sub-Saharan Africa. This...
PURPOSE OF REVIEW
Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne parasitic neglected tropical disease (NTD) endemic in sub-Saharan Africa. This review aims to enhance our understanding of HAT and provide valuable insights to combat this significant public health issue by synthesizing the latest research and evidence.
RECENT FINDINGS
HAT has reached a historical < 1000 cases in 2018. In patients without neurologic symptoms and signs, the likelihood of a severe meningoencephalitic stage is deemed low, obviating the need for a lumbar puncture to guide treatment decisions using fexinidazole.
SUMMARY
Both forms of the disease, gambiense HAT (gHAT) and rhodesiense HAT (rHAT), have specific epidemiology, risk factors, diagnosis, and treatment. Disease management still requires a high index of suspicion, infectious disease expertise, and specialized medical care. Essential stakeholders in health policy are critical to accomplishing the elimination goals of the NTD roadmap for 2021-2030.
PubMed: 38939748
DOI: 10.1007/s40475-023-00304-w -
Journal of Extracellular Biology Oct 2023Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and...
Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and responsible for several millions of deaths. Research on extracellular vesicles (EVs) has increased in recent years and demonstrated that EVs shed by pathogenic parasites interact with host cells playing an important role in the parasite's survival, such as facilitation of infection, immunomodulation, parasite adaptation to the host environment and the transfer of drug resistance factors. Thus, EVs released by parasites mediate parasite-parasite and parasite-host intercellular communication. In addition, they are being explored as biomarkers of asymptomatic infections and disease prognosis after drug treatment. However, most current protocols used for the isolation, size determination, quantification and characterization of molecular cargo of EVs lack greater rigor, standardization, and adequate quality controls to certify the enrichment or purity of the ensuing bioproducts. We are now initiating major guidelines based on the evolution of collective knowledge in recent years. The main points covered in this position paper are methods for the isolation and molecular characterization of EVs obtained from parasite-infected cell cultures, experimental animals, and patients. The guideline also includes a discussion of suggested protocols and functional assays in host cells.
PubMed: 38939734
DOI: 10.1002/jex2.117 -
Forensic Sciences Research Jun 2024Ongoing terrorist attacks in the Sahel region call for strengthening the security system by using human DNA identification technology. In this context, public opinion...
Ongoing terrorist attacks in the Sahel region call for strengthening the security system by using human DNA identification technology. In this context, public opinion must be considered when establishing solid standards and universal safeguards for one of the most invasive forms of surveillance and profiling. For this purpose, we gathered internet users' opinions in Burkina Faso (a country located in the Sahel region) on the use of DNA technology to support criminal investigations. The results revealed that 91.7% (431) of the 470 participants believed that this technology is currently necessary for the Burkina Faso's criminal justice system. However, the respondents expressed concerns about the custody and management of a national forensic DNA database. In this particular security setting, the public opinion of this study may provide leaders and political policymakers with clues for considering genetic fingerprints and implementing an national forensic DNA database to support criminal investigations in Burkina Faso whilst also considering the ethical implications.
PubMed: 38939471
DOI: 10.1093/fsr/owad056 -
Cureus May 2024Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and...
BACKGROUND
Gastroenteritis is a common cause of morbidity and mortality globally. Its cause encompasses a spectrum of agents, including viruses, bacteria, parasites, toxins, and drugs. Viruses account for a considerable portion of gastroenteritis cases across all age groups, typically presenting with symptoms like nausea, vomiting, diarrhea, dehydration, anorexia, and weight loss. While sporadic cases occur, viral gastroenteritis is more frequently observed in outbreaks within closely knit communities such as daycare facilities, nursing homes, and cruise ships. Therefore, it becomes necessary to determine when healthcare providers should consider this condition in their differential diagnosis and to develop the most effective strategy to confirm the diagnosis.
METHODS
De-identified data of patients with gastroenteritis were collected over a five-year period utilizing the Patient Cohort Explorer, an electronic health record at the University of Mississippi Medical Center. Confirmatory laboratory tests employed the BioFire® FilmArray® multiplex polymerase chain reaction for gastrointestinal pathogens. Out of the 22 most common agents associated with gastroenteritis, only viral pathogens, specifically adenovirus, astrovirus, norovirus, rotavirus, and sapovirus, were included in the analysis. When available, histopathology was reviewed.
RESULTS
Among the various causes of gastroenteritis, both infectious and non-infectious, our findings revealed that 25.46% of the cases were linked to viral pathogens. This included a significantly higher percentage of pediatric patients (72.73%) when compared to adults (27.07%), with a p-value of 0.015. Norovirus genogroups I and II emerged as the most frequently detected viruses across all age groups, with a significant prevalence among adults. No discernible gender-based differences were observed. The histopathological findings included inflammation, ulceration, erosion, architectural distortion, and the pathognomonic viral inclusion bodies associated with adenovirus.
CONCLUSION
Our comprehensive analysis of viral gastroenteritis cases highlights the substantial burden of this condition, particularly among pediatric patients. Norovirus emerges as a prevalent culprit which emphasizes the importance of vigilant surveillance and timely diagnosis, especially in settings where outbreaks are common.
PubMed: 38939260
DOI: 10.7759/cureus.61197 -
Computation (Basel, Switzerland) Jan 2024The prognosis of mixed-lineage leukemia (MLL) has remained a significant health concern, especially for infants. The minimal treatments available for this aggressive...
The prognosis of mixed-lineage leukemia (MLL) has remained a significant health concern, especially for infants. The minimal treatments available for this aggressive type of leukemia has been an ongoing problem. Chromosomal translocations of the KMT2A gene are known as MLL, which expresses MLL fusion proteins. A protein called menin is an important oncogenic cofactor for these MLL fusion proteins, thus providing a new avenue for treatments against this subset of acute leukemias. In this study, we report results using the structure-based drug design (SBDD) approach to discover potential novel MLL-mediated leukemia inhibitors from natural products against menin. The three-dimensional (3D) protein model was derived from Protein Databank (Protein ID: 4GQ4), and EasyModeller 4.0 and I-TASSER were used to fix missing residues during rebuilding. Out of the ten protein models generated (five from EasyModeller and I-TASSER each), one model was selected. The selected model demonstrated the most reasonable quality and had 75.5% of residues in the most favored regions, 18.3% of residues in additionally allowed regions, 3.3% of residues in generously allowed regions, and 2.9% of residues in disallowed regions. A ligand library containing 25,131 ligands from a Chinese database was virtually screened using AutoDock Vina, in addition to three known menin inhibitors. The top 10 compounds including ZINC000103526876, ZINC000095913861, ZINC000095912705, ZINC000085530497, ZINC000095912718, ZINC000070451048, ZINC000085530488, ZINC000095912706, ZINC000103580868, and ZINC000103584057 had binding energies of -11.0, -10.7, -10.6, -10.2, -10.2, -9.9, -9.9, -9.9, -9.9, and -9.9 kcal/mol, respectively. To confirm the stability of the menin-ligand complexes and the binding mechanisms, molecular dynamics simulations including molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) computations were performed. The amino acid residues that were found to be potentially crucial in ligand binding included Phe243, Met283, Cys246, Tyr281, Ala247, Ser160, Asn287, Asp185, Ser183, Tyr328, Asn249, His186, Leu182, Ile248, and Pro250. MI-2-2 and PubChem CIDs 71777742 and 36294 were shown to possess anti-menin properties; thus, this justifies a need to experimentally determine the activity of the identified compounds. The compounds identified herein were found to have good pharmacological profiles and had negligible toxicity. Additionally, these compounds were predicted as antileukemic, antineoplastic, chemopreventive, and apoptotic agents. The 10 natural compounds can be further explored as potential novel agents for the effective treatment of MLL-mediated leukemia.
PubMed: 38938622
DOI: 10.3390/computation12010003 -
Frontiers in Immunology 2024
Topics: Biomarkers; Animals; Humans; Host-Parasite Interactions; Trypanosomiasis; Trypanosomatina; Trypanosoma
PubMed: 38938579
DOI: 10.3389/fimmu.2024.1422067 -
Scientifica 2024This study provides the design of a microencapsulation formula, physicochemical characterization, and antioxidant, antibacterial, and antiplasmodial activities of...
This study provides the design of a microencapsulation formula, physicochemical characterization, and antioxidant, antibacterial, and antiplasmodial activities of microcapsules. The ethanolic extract of was microencapsulated with chitosan (CHI) and sodium tripolyphosphate (Na-TPP) with various stirring times: 60 minutes (CHI60), 90 minutes (CHI90), and 120 minutes (CHI120). The microcapsules were then observed for physicochemical properties using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). The microcapsules were tested for antioxidant activity and antibacterial activity against and using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antiplasmodial bioactivity was assessed through in silico molecular docking. The CHI60 and CHI120 microcapsules exhibited a smaller size and an irregular spherical shape, while the same FTIR profile was observed in CHI90 and CHI120. The bioactivity tests demonstrated that CHI90 exhibited high antibacterial activity against and , while CHI120 exhibited high antioxidant performance. Calcigeroside B and Echinoside B exhibited antiplasmodial activity against the dihydroorotate dehydrogenase (PfDHODH) protein, along with an artemisinin inhibition mechanism. In conclusion, the microcapsules with the CHI90 formula demonstrated the best antibacterial activity, while the CHI120 formula exhibited high antioxidant activity. Two terpenoids, Calcigeroside B and Echinoside B, exhibited the best antiplasmodial activity.
PubMed: 38938546
DOI: 10.1155/2024/5559133 -
Open Veterinary Journal May 2024One zoonotic infectious animal disease is brucellosis. The bacteria that cause brucellosis belong to the genus . Numerous animal and human species are affected by... (Review)
Review
One zoonotic infectious animal disease is brucellosis. The bacteria that cause brucellosis belong to the genus . Numerous animal and human species are affected by brucellosis, with an estimated 500,000 human cases recorded annually worldwide. The occurrence of new areas of infection and the resurgence of infection in already infected areas indicate how dynamically brucellosis is distributed throughout different geographic regions. Bacteria originate from the blood and are found in the reticuloendothelial system, the liver, the spleen, and numerous other locations, including the joints, kidneys, heart, and genital tract. Diagnosis of this disease can be done by bacterial isolation, molecular tests, modified acid-fast stain, rose bengal test (RBT), milk ring test, complement fixation test, enzyme-linked immunosorbent assay, and serum agglutination test. The primary sign of a infection is infertility, which can result in abortion and the birth of a frail fetus that may go on to infect other animals. In humans, the main symptoms are acute febrile illness, with or without localization signs, and chronic infection. Female cattle have a greater risk of contracting Brucella disease. Human populations at high risk of contracting brucellosis include those who care for cattle, veterinarians, slaughterhouse employees, and butchers. Antibiotic treatment of brucellosis is often unsuccessful due to the intracellular survival of and its adaptability in macrophages. A "one health" strategy is necessary to control illnesses like brucellosis.
Topics: Brucellosis; Animals; Zoonoses; Humans; Brucella; Cattle; Global Health
PubMed: 38938422
DOI: 10.5455/OVJ.2024.v14.i5.1 -
Journal of Extracellular Biology Sep 2023Extracellular vesicles (EVs) recently emerged as important players in the pathophysiology of parasitic infections. While the protist parasite can produce EVs, their...
Extracellular vesicles (EVs) recently emerged as important players in the pathophysiology of parasitic infections. While the protist parasite can produce EVs, their role in giardiasis remains obscure. can disrupt gut microbiota biofilms and transform commensal bacteria into invasive pathobionts at sites devoid of colonizing trophozoites via unknown mechanisms. We hypothesized that EVs could modify gut bacterial behaviour via a novel mode of trans-kingdom communication. Our findings indicate that EVs exert bacteriostatic effects on HB101 and TW1, increasing their swimming motility. EVs also decreased the biofilm-forming ability of HB101 but not by TW1, supporting the hypothesis that these effects are, at least in part, bacteria-selective. HB101 and TW1 exhibited increased adhesion/invasion onto small intestine epithelial cells when exposed to EVs. EVs labelled with PKH67 revealed colocalization with HB101 and TW1 bacterial cells. Small RNA sequencing revealed a high abundance of ribosomal RNA (rRNA)- and transfer RNA (tRNA)-derived small RNAs, short-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) within EVs. Proteomic analysis of EVs uncovered the presence of RNA chaperones and heat shock proteins that can facilitate the thermal stability of EVs and its sRNA cargo, as well as protein-modifying enzymes. In vitro, RNase heat-treatment assays showed that total RNAs in EVs, but not proteins, are responsible for modulating bacterial swimming motility and biofilm formation. small RNAs of EVs, but not proteins, were responsible for the increased bacterial adhesion to intestinal epithelial cells induced upon exposure to EVs. Together, the findings indicate that EVs contain a heat-stable, RNase-sensitive cargo that can trigger the development of pathobiont characteristics in Enterobacteria, depicting a novel trans-kingdom cross-talk in the gut.
PubMed: 38938375
DOI: 10.1002/jex2.109