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Archives of Microbiology Jun 2024The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic... (Review)
Review
The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies.
Topics: Anti-Bacterial Agents; Phytochemicals; Bacteria; Drug Resistance, Multiple, Bacterial; Bacterial Infections; Plant Extracts; Humans
PubMed: 38913205
DOI: 10.1007/s00203-024-04035-y -
International Journal of Pharmaceutics Jun 2024Wet bead milling (WBM) is one of the main approaches for manufacturing long acting injectable (LAI) suspensions, wherein the particle size of an Active Pharmaceutical...
Wet bead milling (WBM) is one of the main approaches for manufacturing long acting injectable (LAI) suspensions, wherein the particle size of an Active Pharmaceutical Ingredient (API) is reduced in a liquid vehicle via grinding. A common challenge observed during WBM is long milling time to achieve target particle size, resulting in poor milling efficiency. The objective of this work was to identify potential API attributes predictive of milling efficiency during WBM. In this study, physical and mechanical properties of nine APIs were characterized. Formulations with these APIs were manufactured using WBM. Bulk Young's Modulus was identified to have a significant influence on the rate of particle attrition. The rank order of Young's Moduli of the APIs was consistent with that of milling efficiency, estimated by an empirical function defined in this study called Milling Resistance (ϕ), representing the holistic impact of milling time, tip speed, bead loading, and batch to chamber volume ratio. The identification of such intrinsic material properties, which provide an early evaluation of potential manufacturing risks, is beneficial to product development, as these assessments can be performed with limited quantities of materials and help identify and design out scale-up challenges.
PubMed: 38909922
DOI: 10.1016/j.ijpharm.2024.124365 -
American Journal of Preventive Medicine Jun 2024People experiencing homelessness (PEH) are highly vulnerable to discrimination and violence, which impact physical and mental health. The study examines past-month...
INTRODUCTION
People experiencing homelessness (PEH) are highly vulnerable to discrimination and violence, which impact physical and mental health. The study examines past-month discrimination and violence against PEH in Los Angeles County (LAC).
METHODS
332 PEH in LAC were surveyed about their past-month experiences with discrimination, physical violence, and sexual violence from April-July 2023. Analyses were conducted in 2023.
RESULTS
31.8% of respondents reported experiencing discrimination daily and 53.9% reported it weekly, whereas rates of lifetime discrimination in studies of general populations of minoritized groups range between 13-60%. Nearly half of respondents who reported experiencing discrimination (49.6%) believed that their housing situation was the reason they were targeted. Victimization was also common, with 16.0% of participants experiencing physical violence and 7.5% experiencing sexual violence in the past 30 days. These rates of past-month victimization are high when compared to past-year physical violence (3.0%) and sexual violence (0.24%) among general populations in major U.S. cities. In multivariate regression analyses, discrimination was associated with being unsheltered in a vehicle (p<0.05) or outdoors (p<0.001), weekly illicit drug use (p<0.01), and psychological distress (p<0.001); violent victimization was associated with being sheltered (p<0.05) or unsheltered outdoors (p<0.001), physical health conditions (p<0.05), and psychological distress (p<0.01); and sexual victimization was associated with non-male gender (p<0.05) and being unsheltered outdoors (p<0.05). Discrimination and victimization outcomes were not associated with any race/ethnicity, sexual orientation, or time homeless characteristics.
CONCLUSIONS
Study findings highlight the dangers of homelessness in the U.S., particularly for those who are unsheltered outdoors.
PubMed: 38908722
DOI: 10.1016/j.amepre.2024.06.016 -
Lupus Science & Medicine Jun 2024Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is...
OBJECTIVE
Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear.
METHODS
MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice.
RESULTS
ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1β in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys.
CONCLUSION
RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.
Topics: Animals; Lupus Erythematosus, Systemic; Mice, Inbred MRL lpr; Receptor-Interacting Protein Serine-Threonine Kinases; Mice; Mice, Inbred C57BL; Disease Models, Animal; Graft vs Host Disease; Cytokines; Female; Antibodies, Antinuclear; Lupus Nephritis; T-Lymphocytes; Spleen
PubMed: 38906550
DOI: 10.1136/lupus-2024-001146 -
Frontiers in Immunology 2024Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability,... (Review)
Review
Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by and ImpA secreted by , as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αβ on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
Topics: Extracellular Vesicles; Phagocytosis; Humans; Animals; Bacterial Proteins; Neoplasms; Integrin alphaVbeta3; Hyaluronan Receptors; Pseudomonas aeruginosa
PubMed: 38903499
DOI: 10.3389/fimmu.2024.1418061 -
Frontiers in Bioengineering and... 2024Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer....
Chemotherapy drugs like doxorubicin (Dox) are widely used in middle-income countries around the world to treat various types of cancers, including breast cancer. Although they are toxic, they are still widely used to treat cancer. Delivering chemotherapy drugs directly to cancer cells to reduce side effects remains a challenge. Moreover, modern research gave rise to cancer stem cell theory, which implicated cancer stem cells in tumor initiation, progression, and relapse. This makes it imperative to target cancer stem cells to achieve complete remission. Our work highlights the development of an exosome-based targeted drug delivery vehicle. These exosomes were isolated from mature dendritic cells (mDCs) and encapsulated with doxorubicin (ExoDS). Our results showed that ExoDS specifically targeted breast cancer cells and breast cancer stem cells. Further analysis revealed that ExoDS did not induce any significant apoptosis in healthy mammary cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals and breast cancer patients. ExoDS was also found to target circulating tumor cells (CTCs) isolated from patient blood. ExoDS also showed equal efficiency compared to free doxorubicin . We also observed that ExoDS reduced the expression of cancer stem cell markers in murine tumor tissues. Altogether, this work provides novel insights into how mDC-derived exosomes can be used to specifically target cancer cells and cancer stem cells.
PubMed: 38903193
DOI: 10.3389/fbioe.2024.1362681 -
Scientific Reports Jun 2024Mononuclear phagocytes (MNP), including macrophages and dendritic cells form an essential component of primary responses to environmental hazards and toxic exposures....
Mononuclear phagocytes (MNP), including macrophages and dendritic cells form an essential component of primary responses to environmental hazards and toxic exposures. This is particularly important in disease conditions such as asthma and allergic airway disease, where many different cell types are present. In this study, we differentiated CD34+ haematopoietic stem cells towards different populations of MNP in an effort to understand how different cell subtypes present in inflammatory disease microenvironments respond to the common allergen house dust mite (HDM). Using single cell mRNA sequencing, we demonstrate that macrophage subtypes MC and MLC display different patterns of gene expression after HDM challenge, noted especially for the chemokines CXCL5, CXCL8, CCL5 and CCL15. MLC alternatively activated macrophages displayed the greatest changes in expression, while neutrophil and monocyte populations did not respond. Further work investigated how pollutant diesel exhaust particles could modify these transcriptional responses and revealed that CXC but not CC type chemokines were further upregulated. Through the use of diesel particles with adsorbed material removed, we suggest that soluble pollutants on these particles are the active constituents responsible for the modifying effects on HDM. This study highlights that environmental exposures may influence tissue responses dependent on which MNP cell type is present, and that these should be considerations when modelling such events in vitro. Understanding the nuanced responsiveness of different immune cell types to allergen and pollutant exposure also contributes to a better understanding of how these exposures influence the development and exacerbation of human disease.
Topics: Animals; Pyroglyphidae; Humans; Phagocytes; Macrophages; Allergens; Vehicle Emissions; Hematopoietic Stem Cells; Dendritic Cells; Gene Expression Regulation
PubMed: 38902328
DOI: 10.1038/s41598-024-64783-1 -
Traffic Injury Prevention Jun 2024The objective of this study was to describe fatal pedestrian injury patterns in youth aged 15 to 24 years old and correlate them with motor vehicle collision (MVC)...
OBJECTIVE
The objective of this study was to describe fatal pedestrian injury patterns in youth aged 15 to 24 years old and correlate them with motor vehicle collision (MVC) dynamics and pedestrian kinematics using data from medicolegal death investigations of MVCs occurring in the current Canadian motor vehicle (MV) fleet.
METHODS
Based on a systematic literature review, MVC-pedestrian injuries were collated in an injury data collection form (IDCF). The IDCF was coded using the Abbreviated Injury Scale (AIS) 2015 revision. The AIS of the most frequent severe injury was noted for individual body regions. The Maximum AIS (MAIS) was used to define the most severe injury to the body overall and by body regions (MAISBR). This study focused on serious to maximal injuries (AIS 3-6) that had an increasing likelihood of causing death. The IDCF was used to extract collision and injury data from the Office of the Chief Coroner for Ontario (OCCO) database of postmortem examinations done at the Provincial Forensic Pathology Unit (PFPU) in Toronto, Canada, and other provincial facilities between 2013 and 2019. Injury data were correlated with data about the MVs and MV dynamics and pedestrian kinematics.The study was approved by the Western University Health Science Research Ethics Board (Project ID: 113440; Lawson Health Research Institute Approval No. R-19-066).
RESULTS
There were 88 youth, including 54 (61.4%) males and 34 (38.6%) females. Youth pedestrians comprised 13.1% (88/670) of all autopsied pedestrians. Cars ( = 25/88, 28.4%) were the most frequent type of vehicle in single-vehicle impacts, but collectively vehicles with high hood edges (i.e., greater distance between the ground and hood edge) were in the majority. Forward projection ( = 34/88, 38.6%) was the most frequent type of pedestrian kinematics. Regardless of the type of vehicle, there was a tendency in most cases for the median MAISBR ≥ 3 to involve the head and thorax. A similar trend was seen in most of the pedestrian kinematics involving the various frontal impacts. Of the 88 cases, at least 63 (71.6%) were known to be engaged in risk-taking behaviors (e.g., activity on roadway). At least 12 deaths were nonaccidental (8 suicides and 4 homicides). Some activities may have been impairment related, because 26/63 (41.3%) pedestrians undertaking risk-taking behavior on the roadway were impaired. Toxicological analyses revealed that over half of the cases (47/88, 53.4%) tested positive for a drug that could have affected behavior. Ethanol was the most common. Thirty-one had positive blood results.
CONCLUSION
A fatal dyad of head and thorax trauma was observed for pedestrians struck by cars. For those pedestrians hit by vehicles with high hood edges, which were involved in the majority of cases, a fatal triad of injuries to the head, thorax, and abdomen/retroperitoneum was observed. Most deaths occurred from frontal collisions and at speeds more than 35 km/h.
PubMed: 38900934
DOI: 10.1080/15389588.2024.2351603 -
Nanomedicine (London, England) Jun 2024Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal... (Review)
Review
Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150 nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.
PubMed: 38900607
DOI: 10.1080/17435889.2024.2354159 -
European Journal of Nuclear Medicine... Jun 2024
Correction to: HER2-directed antibodies, affibodies and nanobodies as drug-delivery vehicles in breast cancer with a specific focus on radioimmunotherapy and radioimmunoimaging.
PubMed: 38900309
DOI: 10.1007/s00259-024-06792-w