Norditerpene natural products from subterranean fungi with anti-parasitic activity.

is a common, waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently there are no effective therapeutics to treat cryptosporidiosis in at-risk populations. Since natural products are a known source of anti-parasitic compounds, we screened a library of extracts and pure natural product compounds isolated from bacteria and fungi collected from subterranean environments for activity against .

Microbial DNA Profiles of Bacterial Extracellular Vesicles from 3D Salivary Polymicrobial Biofilms - A Pilot Study.

With the advent of multi-layered and 3D scaffolds, the understanding of microbiome composition and pathogenic mechanisms within polymicrobial biofilms is continuously evolving. A fundamental component in mediating the microenvironment and bacterial-host communication within the biofilm are bilayered nanoparticles secreted by bacteria, known as bacterial extracellular vesicles (BEVs), which transport key biomolecules including proteins, nucleic acids, and metabolites. Their characteristics and microbiome profiles are yet to be explored in the context of in vitro salivary polymicrobial biofilm.

Immunoaffinity-enriched salivary small extracellular vesicles in periodontitis.

Aim: aliva extracellular vesicles (EVs) serve as a significant reservoir of biomarkers that may be of clinical use in disease diagnosis. Saliva, however, contains EVs of both host- and bacterial- origin. Identifying suitable EVs for disease diagnosis involves enriching host EVs and limiting non-host contamination with effective isolation methods.

Nanoformulated fenbendazole as an attractive approach for treating neurocysticercosis: and studies.

Purpose: This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energetic metabolism of cysticerci, following an intracranial inoculation in mice.

Methods: Fenbendazole was nanoformulated by the antisolvent method using poloxamers 188 and 407 as stabilizers. The nanosuspensions were lyophilized without cryoprotectants and the nanocrystals were characterized in terms of particle size, zeta potential, and dissolution performance.

Formulation and optimization of chitosan-based amorphous fenbendazole microparticles through a design of experiment approach.

Fenbendazole is a broad-spectrum anthelmintic used in veterinary medicine. It is a lipophilic benzimidazole derivative with low water solubility (<0.1 g/L) recently studied for repositioning in cancer treatment.

Exploring the Dissolution, Solid-state Properties, and Long-term Storage Stability of Cryoprotectant-free Fenbendazole Nanoparticles.

Fenbendazole is an antiparasitic drug widely used in veterinary medicine to treat parasitic infections caused in animals like cattle, horses, sheep, and dogs. Recently, it has been repositioned as a potential alternative for cancer treatment. However, it is a highly hydrophobic molecule (0.

High-throughput surface epitope immunoaffinity isolation of extracellular vesicles and downstream analysis.

Extracellular vesicles (EVs), including exosomes, have significant potential for diagnostic and therapeutic applications. The lack of standardized methods for efficient and high-throughput isolation and analysis of EVs, however, has limited their widespread use in clinical practice. Surface epitope immunoaffinity (SEI) isolation utilizes affinity ligands, including antibodies, aptamers, or lectins, that target specific surface proteins present on EVs.

In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis.

Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen.

Antimicrobial isoflavans and other metabolites of Dalea nana.

The phytochemical investigation of extracts from Dalea nana roots and aerial parts led to the isolation of thirteen phenolic compounds. Three previously undescribed isoflavans, named verdeans A-C (1, 3, and 7), were characterized. Two additional isoflavans (2 and 5) were previously undescribed enantiomers of known compounds.

Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters.

Cell culture-conditioned medium (CCM) is a valuable source of extracellular vesicles (EVs) for basic scientific, therapeutic and diagnostic applications. Cell culturing parameters affect the biochemical composition, release and possibly the function of CCM-derived EVs (CCM-EV). The CCM-EV task force of the Rigor and Standardization Subcommittee of the International Society for Extracellular Vesicles aims to identify relevant cell culturing parameters, describe their effects based on current knowledge, recommend reporting parameters and identify outstanding questions.

Differential response of placental cells to high D-glucose and its impact on extracellular vesicle biogenesis and trafficking via small GTPase Ras-related protein RAB-7A.

Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells.

No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

Introduction: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.

Methods: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers.

Enhancing precision targeting of ovarian cancer tumor cells in vivo through extracellular vesicle engineering.

Extracellular vesicles (EVs) function as natural mediators of intercellular communication, secreted by cells to facilitate cell-cell signaling. Due to their low toxicity, immunogenicity, biodegradability, and potential to encapsulate therapeutic drugs, EVs hold significant therapeutic promise. Nevertheless, their limited targeting ability often diminishes their therapeutic impact.

Outlining the Hidden Curriculum: Perspectives on Successfully Navigating Scientific Conferences.

Scientific conferences and meetings are valuable opportunities for researchers to network, communicate, and develop knowledge. For early career scientists, conferences can also be intimidating, confusing, and overwhelming, especially without having adequate preparation or experience. In this Perspective, we provide advice based on previous experiences navigating scientific meetings and conferences.

Conformational analysis and spectroscopic properties of antichagasic nifurtimox.

Considering the health relevance of Chagas' disease, recent research efforts have focused on developing more efficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFX through conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemble sampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.

Unveiling clinical applications of bacterial extracellular vesicles as natural nanomaterials in disease diagnosis and therapeutics.

Bacterial extracellular vesicles (BEVs) are naturally occurring bioactive membrane-bound nanoparticles released by both gram-negative and gram-positive bacterial species, exhibiting a multifaceted role in mediating host-microbe interactions across various physiological conditions. Increasing evidence supports BEVs as essential mediators of cell-to-cell communicaiton, influencing bacterial pathogenicity, disease mechanisms, and modulating the host immune response. However, the extent to which these BEV-mediated actions can be leveraged to predict disease onset, guide treatment strategies, and determine clinical outcomes remains uncertain, particularly in terms of their clinical translation potentials.

Correction: Soda et al. Electrochemical Detection of Global DNA Methylation Using Biologically Assembled Polymer Beads. 2021, , 3787.

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IFPA Joan Hunt Senior Award in Placentology lecture: Extracellular vesicle signalling and pregnancy.

The field of extracellular vesicle (EV) signalling has the potential to transform our understanding of maternal-fetal communication and affords new opportunities for non-invasive prenatal testing and therapeutic intervention. EVs have been implicated in implantation, placentation, maternal adaptation to pregnancy and complications of pregnancy, being detectable in maternal circulation as early as 6 weeks of pregnancy. EVs of differing biogenic origin, composition and bioactivity are released by cells to maintain homoeostasis.

Promises, Pitfalls, and Clinical Applications of Artificial Intelligence in Pediatrics.

Artificial intelligence (AI) broadly describes a branch of computer science focused on developing machines capable of performing tasks typically associated with human intelligence. Those who connect AI with the world of science fiction may meet its growing rise with hesitancy or outright skepticism. However, AI is becoming increasingly pervasive in our society, from algorithms helping to sift through airline fares to substituting words in emails and SMS text messages based on user choices.

Comprehensive strategy for identifying extracellular vesicle surface proteins as biomarkers for chronic kidney disease.

Chronic kidney disease (CKD) poses a significant health burden worldwide. Especially, obesity-induced chronic kidney disease (OCKD) is associated with a lack of accuracy in disease diagnostic methods. The identification of reliable biomarkers for the early diagnosis and monitoring of CKD and OCKD is crucial for improving patient outcomes.

Advances in extracellular vesicles as mediators of cell-to-cell communication in pregnancy.

Cell-to-cell communication mediated by Extracellular Vesicles (EVs) is a novel and emerging area of research, especially during pregnancy, in which placenta derived EVs can facilitate the feto-maternal communication. EVs comprise a heterogeneous group of vesicle sub-populations with diverse physical and biochemical characteristics and originate by specific biogenesis mechanisms. EVs transfer molecular cargo (including proteins, nucleic acids, and lipids) between cells and are critical mediators of cell communication.

Early-Pregnancy Serum Maternal and Placenta-Derived Exosomes miRNAs Vary Based on Pancreatic β-Cell Function in GDM.

Context: Pancreatic β-cell function impairment is a key mechanism for developing gestational diabetes mellitus (GDM). Maternal and placental exosomes regulate maternal and placental responses during hyperglycemia. Studies have associated exosomal micro-RNAs (miRNAs) with GDM development.

Chemically-Induced Lipoprotein Breakdown for Improved Extracellular Vesicle Purification.

Extracellular vesicles (EVs) are nanosized biomolecular packages involved in intercellular communication. EVs are released by all cells, making them broadly applicable as therapeutic, diagnostic, and mechanistic components in (patho)physiology. Sample purity is critical for correctly attributing observed effects to EVs and for maximizing therapeutic and diagnostic performance.

Melt crystallization and thermal degradation profile of the antichagasic drug nifurtimox.

Despite nifurtimox (NFX) being a traditional drug for treating Chagas disease, some of its physicochemical properties are still unknown, especially its thermal behavior, which brings important outcomes regarding stability and compatibility. In this work, a comprehensive study of NFX's thermal properties was conducted to assist incremental innovations that can improve the efficacy of this drug in novel pharmaceutical products. For this purpose, thermal analyses associated with spectroscopy and spectrometry techniques were used.