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ACS Applied Materials & Interfaces Jun 2024Magnetomicelles were produced by the self-assembly of magnetite iron oxide nanoflowers and the amphiphilic poly(styrene)--poly(acrylic acid) block copolymer to deliver a...
Magnetomicelles were produced by the self-assembly of magnetite iron oxide nanoflowers and the amphiphilic poly(styrene)--poly(acrylic acid) block copolymer to deliver a multifunctional theranostic agent. Their bioprocessing by cancer cells was investigated in a three-dimensional spheroid model over a 13-day period and compared with nonencapsulated magnetic nanoflowers. A degradation process was identified and monitored at various scales, exploiting different physicochemical fingerprints. At a collective level, measurements were conducted using magnetic, photothermal, and magnetic resonance imaging techniques. At the nanoscale, transmission electron microscopy was employed to identify the morphological integrity of the structures, and X-ray absorption spectroscopy was used to analyze the degradation at the crystalline phase and chemical levels. All of these measurements converge to demonstrate that the encapsulation of magnetic nanoparticles in micelles effectively mitigates their degradation compared to individual nonencapsulated magnetic nanoflowers. This protective effect consequently resulted in better maintenance of their therapeutic photothermal potential. The structural degradation of magnetomicelles occurred through the formation of an oxidized iron phase in ferritin from the magnetic nanoparticles, leaving behind empty spherical polymeric ghost shells. These results underscore the significance of encapsulation of iron oxides in micelles in preserving nanomaterial integrity and regulating degradation, even under challenging physicochemical conditions within cancer cells.
PubMed: 38943572
DOI: 10.1021/acsami.4c08727 -
Hepatology Research : the Official... Jun 2024Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell...
Cytokine release syndrome following durvalumab and tremelimumab in advanced hepatocellular carcinoma: A case report with cytokine and damage-associated molecular pattern analysis.
Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell hyperactivation caused by therapeutic agents, pathogens, cancers, and autoimmune diseases. In recent years, CRS has emerged as a rare, but significant, immune-related adverse event linked to immune checkpoint inhibitor therapy. Furthermore, several previous studies suggested that damage-associated molecular patterns (DAMPs) could be involved in malignancy-related CRS. In this study, we present a case of severe CRS following combination therapy with durvalumab and tremelimumab for advanced hepatocellular carcinoma, which recurred during treatment, as well as an analysis of cytokine and DAMPs trends. A 35-year-old woman diagnosed with hepatocellular carcinoma underwent a partial hepatectomy. Due to cancer recurrence, she started a combination of durvalumab and tremelimumab. Then, 29 days post-administration, she developed fever and headache, initially suspected as sepsis. Despite antibiotics, her condition worsened, leading to disseminated intravascular coagulation and hemophagocytic syndrome. The clinical course and elevated serum interleukin-6 levels led to a CRS diagnosis. Steroid pulse therapy was administered, resulting in temporary improvement. However, she relapsed with increased interleukin-6, prompting tocilizumab treatment. Her condition improved, and she was discharged on day 22. Measurements of inflammatory cytokines interferon-γ, tumor necrosis factor-α, and DAMPs, along with interleukin-6, using preserved serum samples, confirmed marked elevation at CRS onset. CRS can occur after the administration of any immune checkpoint inhibitor, with the most likely trigger being the release of DAMPs associated with tumor collapse.
PubMed: 38943555
DOI: 10.1111/hepr.14088 -
Technology and Health Care : Official... Jun 2024Uncemented acetabular components are widely used in modern total hip arthroplasty (THA). Modularity has numerous advantages including the ability to use supplementary...
BACKGROUND
Uncemented acetabular components are widely used in modern total hip arthroplasty (THA). Modularity has numerous advantages including the ability to use supplementary screw fixation for the shell, and allow to switch from ceramic to polyethylene (PE) bearings and vice versa, and the use of lipped and face-changing liners.
OBJECTIVE
Despite these advantages, a problem with modular PE liners is dissociation. This is a rare complication in modern implants. The rate of liner dissociation is reported to be very low between 0.17% and 0.8%. Typical symptoms are sudden onset of groin pain in a previously well-functioning hip joint, followed by grinding or clicking sensations during hip joint motions indicating, that the femoral head is articulating with the metal acetabular shell rather than with the PE liner. Any newly observed noise or squeaking from a THA should undergo radiographic investigation to exclude liner dissociation.
CASE PRESENTATION
We present the case of an 88-yearold male patient who developed PE liner dissociation in a cementless THA with a Pinnacle acetabular component six years after the index operation. We recommended revision of the left hip, which was performed two days later. In the interim, the patient was advised to use a pair of crutches. During revision surgery, it was observed that the metal head made contact with the cementless cup shell without damaging it from a macroscopic standpoint. Consequently, a simple exchange of the PE liner was conducted, and a 36 mm metal head was implanted due to scratches on the original head.
CONCLUSION
Early diagnosis facilitates a straightforward exchange of the liner along with the head, potentially preserving the osseous integrated cup shell and stem integrity. Routine radiologic follow-up allows to distinguish between PE liner dissociation and severe PE wear.
PubMed: 38943412
DOI: 10.3233/THC-240016 -
Giornale Italiano Di Nefrologia :... Jun 2024Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are...
Prevalence and Risk Factors of Heart Failure with Preserved Ejection Fraction in Middle-Aged Maintenance Haemodialysis Patients on a Twice-Weekly Schedule: Experience from a Single Indian Centre.
Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are scarce. Estimate the prevalence of heart failure with preserved ejection fraction (HFpEF) in haemodialysis patients Classify cardiac failure and ascertain the risk factors influencing HFpEF in haemodialysis patients. All consenting individuals on haemodialysis over 18 years of age were included. Lung ultrasound was performed as per the LUST study protocol, and the labs were documented. Echocardiographic parameters were measured using two-dimensional (2D ECHO). A total of 102 patients consented to participate in the study, which included 63 males (61.8%) and 39 females (38.2%). The mean patient age was 53 ± 13.1 years. The dialysis vintage of the participants was 38.92 ± 6.947 months. 47 (46.1%) patients had diabetes and 88 (80.4%) had hypertension. ECG findings included sinus rhythm (51/102, 50%), sinus tachycardia (22/102, 21.6%), ST-T wave abnormalities (18/102, 17.6%), and atrial fibrillation (11/102, 10.8%). Heart failure with preserved ejection fraction (HFpEF) was present in 44/102 (43.14%), heart failure with mid-range EF in 14/102 (13.72%), and heart failure with reduced EF in 13/102 (12.7%) patients. The ejection fraction was positively associated with haemoglobin (r = 0.23; p = 0.044), and calcium levels (r = 0.25; p =0 .03). E/lateral e' ratio was positively correlated with NT pro-BNP (r = 0.63; p < 0.001), systolic blood pressure (r = 0.44; p = 0.003) and age (r = 0.353; p = 0.003) and negatively correlated with transferrin saturation (r = -0.353; p = 0.027) and diastolic blood pressure (r = -0.31; p = 0.040). Binary logistic regression analysis revealed that the odds of diastolic dysfunction increased by 2.3 times with each unit increase of creatinine, and diabetics have 7.66 times higher risk for diastolic dysfunction. Binary logistic regression involving ejection fraction (EF) and all laboratory and clinical parameters revealed odds of HFpEF increased by 1.93 times with each unit increase in age, odds of HFpEF increases by 1.53 times with each unit increase in phosphorous and odds of HFpEF increased by 1.1 times with a unit increase of systolic blood pressure. HFpEF is the predominant form of heart failure in haemodialysis patients. Haemoglobin and calcium were positively associated with ejection fraction. Advancing age, elevated creatinine and diabetes mellitus levels are independent predictors of diastolic dysfunction in haemodialysis patients.
Topics: Humans; Male; Female; Heart Failure; Middle Aged; Stroke Volume; Renal Dialysis; Prevalence; Risk Factors; India; Adult; Aged; Kidney Failure, Chronic
PubMed: 38943322
DOI: No ID Found -
Environmental Microbiology Reports Aug 2024Copper homeostasis is a fundamental process in organisms, characterised by unique pathways that have evolved to meet specific needs while preserving core resistance...
Copper homeostasis is a fundamental process in organisms, characterised by unique pathways that have evolved to meet specific needs while preserving core resistance mechanisms. While these systems are well-documented in model bacteria, information on copper resistance in species adapted to cold environments is scarce. This study investigates the potential genes related to copper homeostasis in the genome of Bizionia argentinensis (JUB59-T), a psychrotolerant bacterium isolated from Antarctic seawater. We identified several genes encoding proteins analogous to those crucial for copper homeostasis, including three sequences of copper-transport P1B-type ATPases. One of these, referred to as BaCopA1, was chosen for cloning and expression in Saccharomyces cerevisiae. BaCopA1 was successfully integrated into yeast membranes and subsequently extracted with detergent. The purified BaCopA1 demonstrated the ability to catalyse ATP hydrolysis at low temperatures. Structural models of various BaCopA1 conformations were generated and compared with mesophilic and thermophilic homologous structures. The significant conservation of critical residues and structural similarity among these proteins suggest a shared reaction mechanism for copper transport. This study is the first to report a psychrotolerant P1B-ATPase that has been expressed and purified in a functional form.
Topics: Copper; Cold Temperature; Saccharomyces cerevisiae; Bacterial Proteins; Antarctic Regions; Adenosine Triphosphatases; Genome, Bacterial; Seawater; Copper-Transporting ATPases; Sulfolobaceae
PubMed: 38943264
DOI: 10.1111/1758-2229.13278 -
American Journal of Botany Jun 2024Theory predicts and empirical studies have shown that ecologically manipulated communities with high species diversity are resistant to invasion, but do these...
PREMISE
Theory predicts and empirical studies have shown that ecologically manipulated communities with high species diversity are resistant to invasion, but do these predictions and results hold true when applied to highly competitive invaders in natural communities? Few studies of diversity-mediated invasion resistance have measured both invasion resistance and invader impact in the same study.
METHODS
We used a two-year field experiment to test: (1) diversity-mediated competitive resistance to patch expansion by the grass, Microstegium vimineum; and (2) the competitive effect of M. vimineum on resident plant diversity. We examined responses of M. vimineum to two native plant density-reduction treatments that had opposite effects on species diversity: (1) reducing species richness via the removal of rare species; and (2) reducing dominance by reducing the density of the dominant resident species. We examined the effects of M. vimineum reduction by pre-emergent herbicide on resident diversity in the second year of the study.
RESULTS
Neither rare species removal nor dominant species reduction significantly increased M. vimineum density (relative growth rate). The pre-emergent herbicide dramatically reduced M. vimineum in year 2 of the study, but not most resident plants, which were perennials and indirectly benefited from the herbicide at a more productive site, presumably due to reduced competition from M. vimineum.
CONCLUSIONS
Diversity-mediated resistance did not effectively deter invasion by a highly competitive invader. In the case of M. vimineum and at more productive sites, it would appear that nearly complete removal of this invader is necessary to preserve plant species diversity.
PubMed: 38943238
DOI: 10.1002/ajb2.16362 -
Particle and Fibre Toxicology Jun 2024Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have...
BACKGROUND
Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project.
RESULTS
Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV and FEF, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1β and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV/FVC ratio. This pattern was not observed for other pulmonary function parameters.
CONCLUSIONS
Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.
Topics: Humans; Male; Nanostructures; Female; Occupational Exposure; Adult; Inhalation Exposure; Middle Aged; Lung; Pneumonia; Forced Expiratory Volume; Respiratory Function Tests; Cytokines; Air Pollutants, Occupational; Europe
PubMed: 38943182
DOI: 10.1186/s12989-024-00589-3 -
Journal of Orthopaedic Surgery and... Jun 2024Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a...
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.
BACKGROUND
Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.
METHODS
Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.
RESULTS
We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.
CONCLUSION
In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.
Topics: Animals; Ferroptosis; Exosomes; NF-E2-Related Factor 2; Cellular Senescence; Rats; Signal Transduction; Phospholipid Hydroperoxide Glutathione Peroxidase; Regeneration; AMP-Activated Protein Kinases; Stem Cells; Tendons; Male; Blood Platelets; Rats, Sprague-Dawley; Rotator Cuff Injuries; Disease Models, Animal
PubMed: 38943181
DOI: 10.1186/s13018-024-04869-8 -
BMC Genomics Jun 2024Despite the fact that introns mean an energy and time burden for eukaryotic cells, they play an irreplaceable role in the diversification and regulation of protein...
Despite the fact that introns mean an energy and time burden for eukaryotic cells, they play an irreplaceable role in the diversification and regulation of protein production. As a common feature of eukaryotic genomes, it has been reported that in protein-coding genes, the longest intron is usually one of the first introns. The goal of our work was to find a possible difference in the biological function of genes that fulfill this common feature compared to genes that do not. Data on the lengths of all introns in genes were extracted from the genomes of six vertebrates (human, mouse, koala, chicken, zebrafish and fugu) and two other model organisms (nematode worm and arabidopsis). We showed that more than 40% of protein-coding genes have the relative position of the longest intron located in the second or third tertile of all introns. Genes divided according to the relative position of the longest intron were found to be significantly increased in different KEGG pathways. Genes with the longest intron in the first tertile predominate in a range of pathways for amino acid and lipid metabolism, various signaling, cell junctions or ABC transporters. Genes with the longest intron in the second or third tertile show increased representation in pathways associated with the formation and function of the spliceosome and ribosomes. In the two groups of genes defined in this way, we further demonstrated the difference in the length of the longest introns and the distribution of their absolute positions. We also pointed out other characteristics, namely the positive correlation between the length of the longest intron and the sum of the lengths of all other introns in the gene and the preservation of the exact same absolute and relative position of the longest intron between orthologous genes.
Topics: Introns; Animals; Humans; Arabidopsis; Spliceosomes
PubMed: 38943073
DOI: 10.1186/s12864-024-10558-x -
Bundesgesundheitsblatt,... Jun 2024The article introduces the issue of psychological assessment and training for driving safety, driving competence, and the mobility of older drivers. The psychological... (Review)
Review
The article introduces the issue of psychological assessment and training for driving safety, driving competence, and the mobility of older drivers. The psychological methods for assessing driving competence and the training approaches for maintaining mobility in old age are outlined and illustrated with examples. Preserving driving ability in old age remains a task for which development needs and research gaps must be specified. Although periodic mandatory examinations based on age do not yield any relevant improvement in enhancing traffic safety, they do not cause harm and are widely accepted. It is desirable to move away from a theory focusing on deficits of older age and instead develop an assessment of the comprehensive functions, abilities, and resources of elderly drivers to help preserve the mobility and participation of that specific demographic in traffic.
PubMed: 38943012
DOI: 10.1007/s00103-024-03919-0