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Annals of Medicine Dec 2024The lung is an important site of extramedullary platelet formation, and megakaryocytes in the lung participate in immune responses in addition to platelet production. In... (Review)
Review
The lung is an important site of extramedullary platelet formation, and megakaryocytes in the lung participate in immune responses in addition to platelet production. In acute lung injury and chronic lung injury, megakaryocytes and platelets play a promoting or protective role through different mechanisms. The authors reviewed the role of megakaryocytes and platelets in common clinical lung injuries with different course of disease and different pathogenic factors in order to provide new thinking for the diagnosis and treatment of lung injuries.
Topics: Megakaryocytes; Humans; Blood Platelets; Acute Lung Injury; Lung Injury; Lung; Animals; Respiratory Distress Syndrome
PubMed: 38902986
DOI: 10.1080/07853890.2024.2362871 -
Applied and Environmental Microbiology Jun 2024, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed...
, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse , is reported not to have reduced fitness following infection. Although laboratory strains of mice have successfully been leveraged to model acute human Lyme disease, the ability of these rodents to model interactions remains understudied. Here, we compared infection of with B31 with infection of the traditional murine models-C57BL/6J and C3H/HeN , which develop signs of inflammation akin to human disease. We find that was able to reach much higher burdens (10- to 30-times higher) in multiple skin sites and that the overall dynamics of infection differed between the two rodent species. We also found that remained transmissive to larval for a far shorter period than either strain. In line with these observations, we found that does launch a modest but sustained inflammatory response against in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected hearts. These observations provide new insight into reservoir species and the enzootic cycle.IMPORTANCEA Lyme disease-causing bacteria, , must alternate between infecting a vertebrate host-usually rodents or birds-and ticks. In order to be successful in that endeavor, the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work, we examine how and one of its primary vertebrate reservoirs, , interact during an experimental infection. We find that appears to colonize its natural host less successfully than conventional laboratory mouse models, which aligns with a sustained seemingly anti-bacterial response by against the microbe. These data enhance our understanding of host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of in nature.
PubMed: 38899883
DOI: 10.1128/aem.00822-24 -
Clinical Chemistry and Laboratory... Jun 2024The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely...
OBJECTIVES
The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden.
METHODS
25(OH)D, 24,25(OH)D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study.
RESULTS
Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals.
CONCLUSIONS
Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.
PubMed: 38890759
DOI: 10.1515/cclm-2024-0391 -
BMJ Open Jun 2024Urogenital schistosomiasis (UGS) caused by is endemic in Southern Tanzania. The disease has significant implications for both socioeconomic and public health. Because...
BACKGROUND
Urogenital schistosomiasis (UGS) caused by is endemic in Southern Tanzania. The disease has significant implications for both socioeconomic and public health. Because infections with usually peak in childhood, the majority of studies have concentrated on school-aged children leaving other groups such as males which might be continuous reservoir of infection transmission. However, despite its chronic consequences in the male population, the disease has received insufficient attention, especially in sub-Saharan Africa. This study was conducted to describe the previous and current schistosomiasis status among adult males living in high-endemic areas of southern Tanzania DESIGN, SETTING AND PARTICIPANTS: A descriptive cross-sectional study was employed to gather data on the prevalence of UGS among adult men residing at schistosomiasis endemic in the Mtama District Council. Quantitative methods of data collection which included questionnaire and laboratory procedures were used.
RESULTS
Out of 245 participants, macrohaematuria and microhaematuria were found in 12 (4.9%, 95% CI 2.4% to 7.8%) and 66 (26.9%, 95% CI 21.6% to 32.7%) participants, respectively. ova were recovered from the urine samples of 54 (22.0%, 95% CI 16.7% to 27.3%) participants. The median intensity of infection was 20 eggs per 10 mL of urine ranging from 1 to 201 eggs per 10 mL of urine (IQR) 60.5). Out of 245 participants 33 (13.5% 95% CI 9.0% to 17.6%) had light intensity of infection and 21 (38.9%, 95% CI; 25.0% to 52.5%) had heavy intensity of infection. Overall, the prevalence of heavy intensity of infection was 8.6% (95% CI 4.9% to 12.6%). The prevalence and intensity of UGS varied significantly by age, marital status and village of residence.
CONCLUSION
This study sheds light on the prevalence of UGS among adult males in endemic areas of southern Tanzania. The results highlight the urgent need for comprehensive intervention strategies to address the burden of the disease.
Topics: Humans; Male; Tanzania; Cross-Sectional Studies; Schistosomiasis haematobia; Adult; Prevalence; Young Adult; Schistosoma haematobium; Endemic Diseases; Middle Aged; Animals; Adolescent; Hematuria
PubMed: 38889945
DOI: 10.1136/bmjopen-2023-079690 -
Methods in Molecular Biology (Clifton,... 2024The emergence of zoonotic viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2...
The emergence of zoonotic viruses like severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 have significantly impacted global health and economy. The discovery of other viruses in wildlife reservoir species present a threat for future emergence in humans and animals. Therefore, assays that are less reliant on virus-specific information, such as neutralization assays, are crucial to rapidly develop diagnostics, understand virus replication and pathogenicity, and assess the efficacy of therapeutics against newly emerging viruses. Here, we describe the discontinuous median tissue culture infectious dose 50 (TCID) assay to quantitatively determine the titer of any virus that can produce a visible cytopathic effect in infected cells.
Topics: Animals; Humans; Cytopathogenic Effect, Viral; SARS-CoV-2; Chlorocebus aethiops; COVID-19; Vero Cells; Virus Replication; Tissue Culture Techniques
PubMed: 38888774
DOI: 10.1007/978-1-0716-3890-3_8 -
Journal of Environmental Health Science... Jun 2024Landfill leachate contains antibiotic resistance genes (ARGs) and microplastics (MPs), making it an important reservoir. However, little research has been conducted on... (Review)
Review
Landfill leachate contains antibiotic resistance genes (ARGs) and microplastics (MPs), making it an important reservoir. However, little research has been conducted on how ARGs are enriched on MPs and how the presence of MPs affects pathogens and ARGs in leachates and soil. MPs possess the capacity to establish unique bacterial populations and assimilate contaminants from their immediate surroundings, generating a potential environment conducive to the growth of disease-causing microorganisms and antibiotic resistance genes (ARGs), thereby exerting selection pressure. Through a comprehensive analysis of scientific literature, we have carried out a practical assessment of this topic. The gathering of pollutants and the formation of dense bacterial communities on microplastics create advantageous circumstances for an increased frequency of ARG transfer and evolution. Additional investigations are necessary to acquire a more profound comprehension of how pathogens and ARGs are enriched, transported, and transferred on microplastics. This research is essential for evaluating the health risks associated with human exposure to these pollutants.
PubMed: 38887766
DOI: 10.1007/s40201-023-00879-6 -
European Journal of Pharmaceutics and... Jun 2024The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill"...
The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.
PubMed: 38885911
DOI: 10.1016/j.ejpb.2024.114353 -
Methods in Molecular Biology (Clifton,... 2024Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for...
Establishing a biofilm infection model in vivo allows a better understanding of the underlying infection mechanisms of bacteria. Here we describe a method for constructing an in vivo biofilm model of Streptococcus suis. The animal modeled is a piglet, which is the natural reservoir of S. suis, and the mode of clinical infection is simulated by intranasal inoculation of S. suis. This model is in line with clinical practice, easy to operate, and has good repeated stability.
Topics: Biofilms; Animals; Streptococcus suis; Swine; Streptococcal Infections; Disease Models, Animal
PubMed: 38884908
DOI: 10.1007/978-1-0716-3898-9_3 -
Research Square Jun 2024Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART...
Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. A novel drug formulation is made whereby a lipid nanoparticle (LNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5). This facilitates myeloid drug depot deposition. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated RPV LNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice. Focused ultrasound allows the decorated LNP to penetrate the blood-brain barrier and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression.
PubMed: 38883780
DOI: 10.21203/rs.3.rs-4433306/v1 -
IMeta Apr 2024The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing...
The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants ( = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-β-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with (25.5%) harboring the most resistance genes. In a further analysis with all available infants ( = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years ( < 0.001). Using a random-forest approach, a set of 34 resistance genes could be used to predict age ( = 68.0%). Leveraging microbial host inference analyses, we inferred the age-dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate-active enzymes from and a decreasing need for during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.
PubMed: 38882494
DOI: 10.1002/imt2.169