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JAMA Network Open Jul 2024
Topics: Humans; Chagas Disease; Male; Female; Health Knowledge, Attitudes, Practice; Adult; Middle Aged; Clinical Competence
PubMed: 38954417
DOI: 10.1001/jamanetworkopen.2024.19906 -
Advances in Experimental Medicine and... Jun 2024According to the World Health Organization vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually. Vectors...
According to the World Health Organization vector-borne diseases account for more than 17% of all infectious diseases, causing more than 700,000 deaths annually. Vectors are organisms that are able to transmit infectious pathogens between humans, or from animals to humans. Many of these vectors are hematophagous insects, which ingest the pathogen from an infected host during a blood meal, and later transmit it into a new host. Malaria, dengue, African trypanosomiasis, yellow fever, leishmaniasis, Chagas disease, and many others are examples of diseases transmitted by insects.Both the diet and the infection with pathogens trigger changes in many metabolic pathways, including lipid metabolism, compared to other insects. Blood contains mostly proteins and is very poor in lipids and carbohydrates. Thus, hematophagous insects attempt to efficiently digest and absorb diet lipids and also rely on a large de novo lipid biosynthesis based on utilization of proteins and carbohydrates as carbon source. Blood meal triggers essential physiological processes as molting, excretion, and oogenesis; therefore, lipid metabolism and utilization of lipid storage should be finely synchronized and regulated regarding that, in order to provide the necessary energy source for these events. Also, pathogens have evolved mechanisms to hijack essential lipids from the insect host by interfering in the biosynthesis, catabolism, and transport of lipids, which pose challenges to reproduction, survival, fitness, and other insect traits.In this chapter, we have tried to collect and highlight the current knowledge and recent discoveries on the metabolism of lipids in insect vectors of diseases related to the hematophagous diet and pathogen infection.
PubMed: 38954247
DOI: 10.1007/5584_2024_811 -
Molecular Diversity Jul 2024Lymphatic filariasis (LF) remains a significant health challenge for populations in developing countries. LF is a parasitic disease transmitted by mosquitoes, mainly...
Comprehensive approach to in silico identification and in vitro validation of anti-filarial hit molecules targeting the dimer interface of thioredoxin peroxidase 1 in Wuchereria bancrofti: a progress in anti-filariasis drug development.
Lymphatic filariasis (LF) remains a significant health challenge for populations in developing countries. LF is a parasitic disease transmitted by mosquitoes, mainly caused by the filarial nematode, Wuchereria bancrofti, prevalent in tropical and subtropical regions. Since the present drugs develop complications, including adverse side effects, lack of specificity, and development of drug resistance, the present study focused on developing the potential anti-filariasis drugs targeting crucial proteins for the nematode life cycle. We have identified the therapeutic compounds by targeting the enzyme thioredoxin peroxidase 1 (WbTPx1), which facilitates the conversion of hydrogen peroxide into water, an essential mechanism by which the nematode survives against oxidative stress in the host. This approach might resolve treatment efficacy and activity difficulties at various stages of filarial parasitic worms. We modeled the structure of WbTPx1 and employed the structure-based virtual screening approach, focusing on the dimer interface region of the protein. ADMET prediction profiles of the non-toxic, top-ranked hits with higher docking scores demonstrate higher affinity to the nematode protein than its human homolog. The molecular dynamic simulation studies show WbTPx1-hit complexes' stability and the intactness of hits in the binding site. Further, in vitro validation of identified hits using Setaria digitata, a cattle nematode, showed better IC and higher inhibition than the standard drug ivermectin, indicating the potential to inhibit enzyme activity and the development of drug candidates for controlling LF.
PubMed: 38954071
DOI: 10.1007/s11030-024-10922-9 -
Indian Journal of Public Health Apr 2024India is at a critical stage to eliminate filariasis. Uncovering the factors governing may help taking appropriate measures to achieve the goal.
BACKGROUND
India is at a critical stage to eliminate filariasis. Uncovering the factors governing may help taking appropriate measures to achieve the goal.
OBJECTIVES
This study evaluated the acceptance of "mass drug administration" (MDA) for prophylaxis against filariasis and the factors facilitating and interfering with it.
MATERIALS AND METHODS
A cross-sectional study was conducted in a tribal endemic area of India from May 2022 to October 2022. A validated 29-item self-administered questionnaire was used to collect the data. Items were grouped under "knowledge," "social processes," "think and feel," "practical factors," and "motivation/hesitancy" domains.
RESULTS
Of 101 participants, majority were aware of the disease (92.1%), its vector (74.3%), at least one disability caused (87.2%), and governmental scheme of MDA (69.3%). Two-thirds never received and 85.1% did not receive MDA within 1 year. 68.3% refused of distribution of MDA to their doorstep. Majority were concerned for getting MDA for self and their family/friends; however, 49.5% showed inability to take independent decision. More than 30% disagreed to get MDA had it been available. The region with the highest concerns for adverse drug effects showed minimum MDA consumption than others (P < 0.05). MDA acceptance/consumption was significantly associated with knowledge about disability caused, distribution of drugs by a health-care representative to doorstep, behavior of the representative, and concerns about potential adverse drug effects.
CONCLUSION
MDA coverage was inadequate in the study population. Level of knowledge, practical difficulties in getting drugs, inapt thinking/concerns, motivation, awareness about disabilities caused, door-to-door drug distribution, and behavior of health-care representative(s), were identified as factors significantly affecting acceptance of MDA.
Topics: Humans; Elephantiasis, Filarial; Cross-Sectional Studies; India; Female; Male; Adult; Health Knowledge, Attitudes, Practice; Mass Drug Administration; Patient Acceptance of Health Care; Middle Aged; Filaricides; Young Adult; Endemic Diseases; Surveys and Questionnaires; Adolescent
PubMed: 38953805
DOI: 10.4103/ijph.ijph_312_23 -
Parasite (Paris, France) 2024Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies...
Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.
Topics: Animals; Cattle; Mali; Schistosoma; Cattle Diseases; Schistosomiasis; Prevalence; Genetic Variation; Genetics, Population; DNA, Helminth
PubMed: 38953782
DOI: 10.1051/parasite/2024035 -
MBio Jul 2024Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells...
Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both and . YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.
PubMed: 38953350
DOI: 10.1128/mbio.01549-24 -
Frontiers in Immunology 2024Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma...
INTRODUCTION
Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.
METHODS
Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.
RESULTS
The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.
CONCLUSION
Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.
Topics: Autoantibodies; Humans; Animals; Receptors, G-Protein-Coupled; Rats; Male; Female; Adult; Hypertension, Pulmonary; Middle Aged; Myocytes, Cardiac; Schistosomiasis mansoni; Schistosoma mansoni; Schistosomiasis
PubMed: 38953035
DOI: 10.3389/fimmu.2024.1404384 -
The Canadian Veterinary Journal = La... Jul 2024A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an...
A 21-year-old retired polo Argentinian thoroughbred horse from a teaching herd was presented for a routine bronchoalveolar lavage demonstration, during which an incidental finding of a granulomatous mass on the dorsal aspect of the epiglottis was made. was suspected from a histological section obtained from an initial biopsy, and the mass was removed laser surgery for cytology and PCR. Sequencing of the PCR amplicons confirmed the diagnosis of A treatment protocol of nebulized voriconazole for 10 d postoperatively was used. Long-term follow-up required 2 more laser surgeries plus oral fluconazole to resolve the remaining fungal spores. However, 2.5 y later, there was no evidence of remaining fungal spores. Key clinical message: Horses from endemic regions can potentially be exposed to Based on its travel history, this horse may have contracted the infection in South America, California, or Alberta. Treatments administered, including diode laser resection, voriconazole antifungal nebulization, and oral fluconazole administration, were successful but required repeated interventions.
Topics: Animals; Horses; Horse Diseases; Voriconazole; Antifungal Agents; Male; Rhinosporidiosis; Nebulizers and Vaporizers; Laser Therapy; Polymerase Chain Reaction; Laryngeal Diseases
PubMed: 38952752
DOI: No ID Found -
Frontiers in Public Health 2024
Topics: Humans; India; Mass Drug Administration; Filariasis; Filaricides; Disease Eradication
PubMed: 38952727
DOI: 10.3389/fpubh.2024.1384131 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jun 2024CRISPR/Cas system, an adaptive immune system with clustered regularly interspaced short palindromic repeats, may interfere with exogenous nucleic acids and protect... (Review)
Review
CRISPR/Cas system, an adaptive immune system with clustered regularly interspaced short palindromic repeats, may interfere with exogenous nucleic acids and protect prokaryotes from external damages, is an effective gene editing and nucleic acid detection tools. The CRISPR/Cas system has been widely applied in virology and bacteriology; however, there is relatively less knowledge about the application of the CRISPR/Cas system in parasitic diseases. The review summarizes the mechanisms of action of the CRISPR/Cas system and provides a comprehensive overview of their application in gene editing and nucleic acid detection of parasitic diseases, so as to provide insights into future studies on parasitic diseases.
Topics: CRISPR-Cas Systems; Gene Editing; Humans; Parasitic Diseases; Animals; Nucleic Acids
PubMed: 38952320
DOI: 10.16250/j.32.1374.2024057