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International Journal of Molecular... Jun 2024Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte...
Chloroquine (CQ) is a 4-aminoquinoline derivative largely employed in the management of malaria. CQ treatment exploits the drug's ability to cross the erythrocyte membrane, inhibiting heme polymerase in malarial trophozoites. Accumulation of CQ prevents the conversion of heme to hemozoin, causing its toxic buildup, thus blocking the survival of Plasmodium parasites. Recently, it has been reported that CQ is able to exert antiviral properties, mainly against HIV and SARS-CoV-2. This renewed interest in CQ treatment has led to the development of new studies which aim to explore its side effects and long-term outcome. Our study focuses on the effects of CQ in non-parasitized red blood cells (RBCs), investigating hemoglobin (Hb) functionality, the anion exchanger 1 (AE1) or band 3 protein, caspase 3 and protein tyrosine phosphatase 1B (PTP-1B) activity, intra and extracellular ATP levels, and the oxidative state of RBCs. Interestingly, CQ influences the functionality of both Hb and AE1, the main RBC proteins, affecting the properties of Hb oxygen affinity by shifting the conformational structure of the molecule towards the R state. The influence of CQ on AE1 flux leads to a rate variation of anion exchange, which begins at a concentration of 2.5 μM and reaches its maximum effect at 20 µM. Moreover, a significant decrease in intra and extracellular ATP levels was observed in RBCs pre-treated with 10 µM CQ vs. erythrocytes under normal conditions. This effect is related to the PTP-1B activity which is reduced in RBCs incubated with CQ. Despite these metabolic alterations to RBCs caused by exposure to CQ, no signs of variations in oxidative state or caspase 3 activation were recorded. Our results highlight the antithetical effects of CQ on the functionality and metabolism of RBCs, and encourage the development of new research to better understand the multiple potentiality of the drug.
Topics: Erythrocytes; Humans; Chloroquine; Hemoglobins; Anion Exchange Protein 1, Erythrocyte; Adenosine Triphosphate; Antimalarials; Caspase 3
PubMed: 38928131
DOI: 10.3390/ijms25126424 -
International Journal of Molecular... Jun 2024Parasites are very widely distributed in the environment and form complex relationships with their hosts, forming host-parasite systems [...].
Parasites are very widely distributed in the environment and form complex relationships with their hosts, forming host-parasite systems [...].
Topics: Humans; Parasitic Diseases; Animals; Host-Parasite Interactions; Parasites
PubMed: 38928081
DOI: 10.3390/ijms25126373 -
International Journal of Molecular... Jun 2024In nature, plants have developed a series of resistance mechanisms to face various external stresses. As understanding of the molecular mechanisms underlying plant...
In nature, plants have developed a series of resistance mechanisms to face various external stresses. As understanding of the molecular mechanisms underlying plant resistance continues to deepen, exploring endogenous resistance in plants has become a hot topic in this field. Despite the multitude of studies on plant-induced resistance, how plants respond to stress under natural conditions remains relatively unclear. To address this gap, we investigated Chinese pine () using pine caterpillar () under natural conditions. Healthy Chinese pine trees, approximately 10 years old, were selected for studying induced resistance in Huangtuliangzi Forestry, Pingquan City, Chengde City, Hebei Province, China. Pine needles were collected at 2 h and 8 h after feeding stimulation (FS) via 10 pine caterpillars and leaf clipping control (LCC), to simulate mechanical damage caused by insect chewing for the quantification of plant hormones and transcriptome and metabolome assays. The results show that the different modes of treatments significantly influence the contents of JA and SA in time following treatment. Three types of differentially accumulated metabolites (DAMs) were found to be involved in the initial response, namely phenolic acids, lipids, and flavonoids. Weighted gene co-expression network analysis indicated that 722 differentially expressed genes (DEGs) are positively related to feeding stimulation and the specific enriched pathways are plant hormone signal transduction and flavonoid biosynthesis, among others. Two TIFY transcription factors ( and ) and a MYB transcription factor () were found to be involved in the interaction between plant hormones, mainly in the context of JA signal transduction and flavonoid biosynthesis. The results of this study provide an insight into how JA activates, serving as a reference for understanding the molecular mechanisms of resistance formation in conifers responding to mandibulate insects.
Topics: Pinus; Animals; Signal Transduction; Plant Growth Regulators; Flavonoids; Gene Expression Regulation, Plant; Larva; Transcriptome; Moths; Biosynthetic Pathways; Plant Leaves; East Asian People
PubMed: 38928063
DOI: 10.3390/ijms25126354 -
International Journal of Molecular... Jun 2024The identification of novel drug targets in plant-parasitic nematodes (PPNs) is imperative due to the loss of traditional nematicides and a lack of replacements....
The identification of novel drug targets in plant-parasitic nematodes (PPNs) is imperative due to the loss of traditional nematicides and a lack of replacements. Chemosensation, which is pivotal for PPNs in locating host roots, has become a focus in nematode behavioral research. However, its underlying molecular basis is still indistinct in such a diverse group of PPNs. To characterize genes participating in chemosensation in the Javanese root-knot nematode , RNA-sequencing of the second-stage juveniles (J2s) treated with tomato root exudate (TRE) for 1 h and 6 h was performed. Genes related to chemosensation in . mainly responded to TRE treatment at 1 h. Moreover, a gene ontology (GO) analysis underscored the significance of the neuropeptide G protein-coupled receptor signaling pathway. Consequently, the repertoire of putative neuropeptides in . , including FMRFamide-like peptides (FLPs), insulin-like peptides (ILPs), and neuropeptide-like peptides (NLPs), were outlined based on a homology analysis. The gene , harboring two neuropeptides, was significantly up-regulated at 1 h TRE treatment. Through peptide synthesis and J2 treatment, one of the two neuropeptides (MjFLP-14-2) was proven to influence the J2 chemotaxis towards tomato root tips. Overall, our study reinforces the potential of nematode neuropeptides as novel targets and tools for root-knot nematode control.
Topics: Animals; Tylenchoidea; Neuropeptides; Plant Roots; Solanum lycopersicum; Plant Diseases; Chemotaxis; Helminth Proteins
PubMed: 38928010
DOI: 10.3390/ijms25126300 -
Genes Jun 2024The grooming behavior of honeybees serves as a crucial auto-protective mechanism against mite infestations. Compared to , demonstrates more effective grooming behavior... (Comparative Study)
Comparative Study
The grooming behavior of honeybees serves as a crucial auto-protective mechanism against mite infestations. Compared to , demonstrates more effective grooming behavior in removing mites from the bodies of infested bees. However, the underlying mechanisms regulating grooming behavior remain elusive. In this study, we evaluated the efficacy of the auto-grooming behavior between and and employed RNA-sequencing technology to identify differentially expressed genes (DEGs) in bee brains with varying degrees of grooming behavior intensity. We observed that exhibited a higher frequency of mite removal between day 5 and day 15 compared to , with day-9 bees showing the highest frequency of mite removal in . RNA-sequencing results revealed the differential expression of the and genes in and the and genes in . Subsequent homology analysis identified the gene and gene of as homologous to the gene and gene of . These DEGs are annotated in the neuroactive ligand-receptor interaction pathway, the glutamatergic synaptic pathway, and the calcium signaling pathway. Moreover, , , , and may be closely related to the auto-grooming behavior of , conferring resistance against infestation. Our results further explain the relationship between honeybee grooming behavior and brain function at the molecular level and provide a reference basis for further studies of the mechanism of honeybee grooming behavior.
Topics: Animals; Bees; Varroidae; Grooming; Brain; Transcriptome; Mite Infestations; Gene Expression Profiling
PubMed: 38927699
DOI: 10.3390/genes15060763 -
Genes Jun 2024Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due... (Review)
Review
Despite remarkable advances in the diagnosis of invasive fungal infections (IFIs), rapid, specific, sensitive, and cost-effective detection methods remain elusive. Due to their stability, ease of production, and specificity to signature molecules of fungal pathogens, short single-stranded sequences of DNA, RNA, and XNA, collectively called aptamers, have emerged as promising diagnostic markers. In this perspective, we summarize recent progress in aptamer-based diagnostic tools for IFIs and discuss how these tools could potentially meet the needs and provide economical and simple solutions for point-of-care for better management of IFIs.
Topics: Humans; Aptamers, Nucleotide; Invasive Fungal Infections; Fungi; SELEX Aptamer Technique
PubMed: 38927669
DOI: 10.3390/genes15060733 -
Genes May 2024Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host's response to...
Infections with gastrointestinal nematodes (GINs) reduce the economic efficiency of sheep operations and compromise animal welfare. Understanding the host's response to GIN infection can help producers identify animals that are naturally resistant to infection. The objective of this study was to characterize the hepatic transcriptome of sheep that had been naturally exposed to GIN parasites. The hepatic transcriptome was studied using RNA-Sequencing technology in animals characterized as high ( = 5) or medium ( = 6) based on their innate immune acute-phase (AP) response phenotype compared with uninfected controls ( = 4), and with biased antibody-mediated (AbMR, = 5) or cell-mediated (CMR, = 5) adaptive immune responsiveness compared to uninfected controls ( = 3). Following the assessment of sheep selected for innate responses, 0, 136, and 167 genes were differentially expressed (DE) between high- and medium-responding animals, high-responding and uninfected control animals, and medium-responding and uninfected control animals, respectively (false discovery rate (FDR) < 0.05, and fold change |FC| > 2). When adaptive immune responses were assessed, 0, 53, and 57 genes were DE between antibody- and cell-biased animals, antibody-biased and uninfected control animals, and cell-biased and uninfected control animals, respectively (FDR < 0.05, |FC| > 2). Functional analyses identified enriched gene ontology (GO) terms and metabolic pathways related to the innate immune response and energy metabolism. Six functional candidate genes were identified for further functional and validation studies to better understand the underlying biological mechanisms of host responses to GINs. These, in turn, can potentially help improve decision making and management practices to increase the overall host immune response to GIN infection.
Topics: Animals; Sheep; Transcriptome; Liver; Nematode Infections; Sheep Diseases; Immunity, Innate; Nematoda; Adaptive Immunity; Gastrointestinal Diseases
PubMed: 38927648
DOI: 10.3390/genes15060713 -
Genes May 2024Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal () species . A full genome was published in 2002, yet 44.6% of its...
BACKGROUND
Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal () species . A full genome was published in 2002, yet 44.6% of its genes have unknown functions. Improving the functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance.
RESULTS
Genes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks in have been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for all genes. We evaluate each inferred network based on how well it predicts existing gene-Gene Ontology (GO) term annotations using network clustering and leave-one-out crossvalidation. We assess overlaps of the different networks' edges (gene co-expression relationships), as well as predicted functional knowledge. The networks' edges are overall complementary: 47-85% of all edges are unique to each network. In terms of the accuracy of predicting gene functional annotations, all networks yielded relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached was below 15%. All networks having low recall means that none of them capture a large amount of all existing gene-GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene-gene interactions and predicted gene-GO term annotations for future use and wet lab validation by the malaria community.
CONCLUSIONS
The different networks seem to capture different aspects of the biology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible.
SUPPLEMENTARY DATA
Attached.
Topics: Plasmodium falciparum; Gene Regulatory Networks; Malaria, Falciparum; Humans; Gene Ontology; Molecular Sequence Annotation; Protozoan Proteins
PubMed: 38927622
DOI: 10.3390/genes15060685 -
Antibiotics (Basel, Switzerland) Jun 2024The appropriate antibiotic treatment of patients with bacterial sepsis in the intensive care unit (ICU) remains a challenge. Considering that current international...
The appropriate antibiotic treatment of patients with bacterial sepsis in the intensive care unit (ICU) remains a challenge. Considering that current international guidelines recommend 7 days of antibiotic therapy as sufficient for most severe infections, our primary outcome was a comparison of clinical response to initial empirical therapy on day 7 and mortality between two groups of septic patients-with appropriate (AEAT) and inappropriate (IEAT) empirical antibiotic therapy according to the in vitro sensitivity of bacteria detected in a blood culture (BC). Adult patients admitted to the ICU between 2020 and 2023, who were diagnosed with sepsis according to the Sequential Organ Failure Assessment (SOFA) score ≥ 2 in association with a suspected or documented infection, were selected for the study. Of the 418 patients, 149 (35.6%) died within 7 days. Although the AEAT group had a lower mortality rate (30.3% vs. 34.2%) and better clinical improvement (52.8% vs. 47.4%) on day 7 after starting empirical antibiotic therapy, there was no significant difference. A causative organism was isolated from BCs in 30% of septic patients, with gram-negative bacteria (GNB) predominating in 60% of cases, and multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria predominantly detected in the BCs of the IEAT group. Although the AEAT group had slightly worse clinical characteristics at the onset of sepsis than the IEAT group, the AEAT group showed faster improvement on days 7 and 14 of sepsis. In this retrospective cross-sectional study, the AEAT group was associated with better clinical response at day 7 after sepsis onset and lower mortality, but without a significant difference. Comorbidities and the type of bacterial pathogen should also be taken into account as they can also contribute to the prediction of the final outcome. These results demonstrate the importance of daily assessment of clinical factors to more accurately predict the clinical outcome of a septic patient.
PubMed: 38927235
DOI: 10.3390/antibiotics13060569 -
Antibiotics (Basel, Switzerland) Jun 2024Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era....
Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS remains limited in Africa, particularly in Rwanda. This study aimed to assess prescription practices, identify areas for improvement, and promote adherence to AMS principles. Conducted at King Faisal Hospital in Rwanda, this qualitative study used semi-structured interviews with eight participants until saturation was reached. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. The first theme was on AMS activities that were working well based on availability of microbiology laboratory results and prescription guidelines as factors influencing antibiotic prescription adjustments. The second theme was related to challenges during the implementation of the AMS program, including the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, and stock-outs of essential antibiotics. The third theme was on the importance of adhering to AMR management guidelines at KFH. The last emerged on recommendations from participants centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program.
PubMed: 38927214
DOI: 10.3390/antibiotics13060548