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Prostaglandins & Other Lipid Mediators Jun 2024The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to... (Review)
Review
The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.
PubMed: 38955261
DOI: 10.1016/j.prostaglandins.2024.106864 -
International Immunopharmacology Jul 2024Cerebral ischemia-induced systemic inflammation and inflammasome-dependent pyroptotic cell death in ileum, causing serious intestinal injury. Glucocorticoid receptor...
Cerebral ischemia-induced systemic inflammation and inflammasome-dependent pyroptotic cell death in ileum, causing serious intestinal injury. Glucocorticoid receptor (GR) mediates the effects of glucocorticoids and participates in inflammation. Escin has corticosteroid-like, neuroprotective, and anti-intestinal dysfunction effects. This study aimed to investigate the effect of Escin on the intestinal barrier injury in rats subjected to middle cerebral artery occlusion (MCAO) and on Caco-2 cells exposed to lipopolysaccharides. The MCAO-caused brain injury was evaluated by assessing neurological function, cerebral infarct volume, and plasma corticosterone (Cort) levels. Intestinal injury was evaluated by observing the histopathological changes, assessing the intestinal barrier function, and determining blood FD4, endotoxin and IL-1β levels. The levels of the tight-junction proteins such as claudin-1, occludin, and ZO-1, and proteins involved in the GR/p38 MAPK/NF-κB pathway and NLRP3-inflammasome activation were evaluated using western blotting or immunofluorescence. Administration of Escin suppressed the cerebral ischemia-induced increases in Garcia-test scores and infarct volume, alleviated the injury to the intestinal barrier, and decreased the levels of Cort, endotoxin, and IL-1β. Additionally, Escin upregulated GR and downregulated phospho(p)-p65, p-p38MAPK, NLRP3, GSDMD-N, and cleaved-caspase-1 in the intestine. The effects of Escin could be suppressed by the GR antagonist RU486 or enhanced by the p38 MAPK antagonist SB203580. We revealed details how Escin improves cerebral ischemia-induced intestinal barrier injury by upregulating GR and thereby inhibiting the pyroptosis induced by NF-κB-mediated NLRP3 activation. This study will provide a experimental foundation for the features of glucocorticoid-like activity and the discovery of new clinical application for Escin.
PubMed: 38955024
DOI: 10.1016/j.intimp.2024.112592 -
International Journal of Surgery Case... Jun 2024Arterial aneurysm is a serious condition caused by weakened arterial walls. Aorto-uni-iliac (AUI) and femorofemoral bypass are safe and effective options for managing...
INTRODUCTION AND IMPORTANCE
Arterial aneurysm is a serious condition caused by weakened arterial walls. Aorto-uni-iliac (AUI) and femorofemoral bypass are safe and effective options for managing abdominal aortic aneurysm (AAA). However, fem-fem bypass leads to longer surgical procedures and introduces additional risks such as graft infection, occlusion, wound complications, and peripheral vascular problems. This report highlights two successful cases of AAA management using the AUI approach without the need for fem-fem bypass.
CASE PRESENTATION
Two male patients, both aged about 70, presented at our medical facility complaining of abdominal pain. Investigations unveiled an approximately 10-cm AAA that was previously undetected. Subsequently, we performed an elective AUI procedure without fem-fem bypass, marking the first instance of this technique being employed in Iran successfully.
CLINICAL DISCUSSION
The placement of an AUI stent graft is generally less technically demanding compared to that of a standard bifurcated graft, especially when anatomical constraints are severe, making the latter difficult or even impossible to deploy. Beside the longer duration of stent deployment, sometimes we encounter contralateral complications to cannulate the main body. The AUI is typically used in emergency situations or when the distal aorta's internal diameter is small. The femoral-femoral bypass is advised in nearly all circumstances.
CONCLUSION
AUI stent grafts are still a viable option for treatments of AAA, especially in cases of severe aortoiliac occlusive disease or comorbidities. AUI without crossover bypass is a viable option in the patients who have stenosis of contralateral iliac artery.
PubMed: 38954972
DOI: 10.1016/j.ijscr.2024.109918 -
Blood Advances Jul 2024Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in pregnant women with sickle cell disease (SCD), despite a lack of robust evidence. TAPS2...
Serial prophylactic exchange blood transfusion (SPEBT) is increasingly used in pregnant women with sickle cell disease (SCD), despite a lack of robust evidence. TAPS2 (Transfusion Antenatally in Pregnant Women with Sickle Cell Disease) study assessed the feasibility and acceptability of conducting a definitive randomized controlled trial of SPEBT (intervention) versus standard care (control) in pregnant women with SCD. Women ≥18 years with SCD, between 6+0 and 18+0 weeks of singleton gestation, were randomized 1:1 to control or intervention every 6-10 weeks throughout pregnancy in seven hospitals in England. The main outcomes evaluated were recruitment rate (primary outcome), acceptability, and retention. Secondary outcomes were safety, maternal and infant clinical outcomes. 194 women were screened over 42 months (extended due to the pandemic), 88 were eligible, and 35 (39.8%) consented to participate. Eighteen participants were randomized to intervention and 17 to control. Follow-up data were collected on all participants. Twelve patients in the intervention group received at least one SPEBT, of these, 11 received 3. The remaining patient was withdrawn from SPEBT due to transfusion reaction. Sixteen control participants required at least one transfusion. There were no statistically significant differences in terms of maternal, infant, or postnatal outcomes. A trend towards a lower incidence of vaso-occlusive crisis, preterm delivery and improved birthweight was observed in the intervention group. Despite the pandemic, this study achieved satisfactory recruitment and retention, confirming its acceptability to participants. TAPS2 demonstrates that it is feasible to perform a definitive international trial of SPEBT in pregnant women with SCD. Trial registration: NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19). TAPS2 trial Protocol: available at https://rdcu.be/drlwc.
PubMed: 38954844
DOI: 10.1182/bloodadvances.2024012923 -
Obstetrics and Gynecology Jul 2024To quantify the association between prophylactic radiologic interventions and perioperative blood loss during cesarean delivery in women with placenta accreta spectrum...
OBJECTIVE
To quantify the association between prophylactic radiologic interventions and perioperative blood loss during cesarean delivery in women with placenta accreta spectrum disorder through a systematic review and network meta-analysis.
DATA SOURCES
On January 3, 2023, a literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science. We also checked ClinicalTrials.gov retrospectively. Prophylactic radiologic interventions to reduce bleeding during cesarean delivery involved preoperative placement of balloon catheters, distal (internal or common iliac arteries) or proximal (abdominal aorta), or sheaths (uterine arteries). The primary outcome was volume of blood loss; secondary outcomes were the number of red blood cell units transfused and adverse events. Studies including women who received an emergency cesarean delivery were excluded.
METHODS OF STUDY SELECTION
Two authors independently screened citations for relevance, extracted data, and assessed the risk of bias of individual studies with the Cochrane Risk of Bias in Non-randomized Studies of Interventions tool.
TABULTATION, INTEGRATION, AND RESULTS
From a total of 1,332 screened studies, 50 were included in the final analysis, comprising 5,962 women. These studies consisted of two randomized controlled trials and 48 observational studies. Thirty studies compared distal balloon occlusion with a control group, with a mean difference in blood loss of -406 mL (95% CI, -645 to -167). Fourteen studies compared proximal balloon occlusion with a control group, with a mean difference of -1,041 mL (95% CI, -1,371 to -710). Sensitivity analysis excluding studies with serious or critical risk of bias provided similar results. Five studies compared uterine artery embolization with a control group, all with serious or critical risk of bias; the mean difference was -936 mL (95% CI, -1,522 to -350). Reported information on adverse events was limited.
CONCLUSION
Although the predominance of observational studies in the included literature warrants caution in interpreting the findings of this meta-analysis, our findings suggest that prophylactic placement of balloon catheters or sheaths before planned cesarean delivery in women with placenta accreta spectrum disorder may, in some cases, substantially reduce perioperative blood loss. Further study is required to quantify the efficacy according to various severities of placenta accreta spectrum disorder and the associated safety of these radiologic interventions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022320922.
PubMed: 38954828
DOI: 10.1097/AOG.0000000000005662 -
CNS Neuroscience & Therapeutics Jul 2024Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary...
AIMS
Ischemic stroke remains a challenge in medical research because of the limited treatment options. Recombinant human tissue plasminogen activator (rtPA) is the primary treatment for recanalization. However, nearly 50% of the patients experience complications that result in ineffective reperfusion. The precise factors contributing to ineffective reperfusion remain unclear; however, recent studies have suggested that immune cells, notably neutrophils, may influence the outcome of rtPA thrombolysis via mechanisms such as the formation of neutrophil extracellular traps. This study aimed to explore the nonthrombolytic effects of rtPA on neutrophils and highlight their contribution to ineffective reperfusion.
METHODS
We evaluated the effects of rtPA treatment on middle cerebral artery occlusion in rats. We also assessed neutrophil infiltration and activation after rtPA treatment in vitro and in vivo in a small cohort of patients with massive cerebral ischemia (MCI).
RESULTS
rtPA increased neutrophil infiltration into the brain microvessels and worsened blood-brain barrier damage during ischemia. It also increased the neutrophil counts of the patients with MCI.
CONCLUSION
Neutrophils play a crucial role in promoting ischemic injury and blood-brain barrier disruption, making them potential therapeutic targets.
Topics: Tissue Plasminogen Activator; Animals; Humans; Male; Neutrophils; Rats; Recombinant Proteins; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Rats, Sprague-Dawley; Aged; Blood-Brain Barrier; Cell Movement; Female; Neutrophil Infiltration; Middle Aged; Brain Ischemia; Disease Models, Animal
PubMed: 38954749
DOI: 10.1111/cns.14825 -
Proceedings of the National Academy of... Jul 2024The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone...
The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR mouse line) for noninvasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss in both aged and young adult brains, accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at 1 mo postablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts (NBs) following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the middle cerebral artery occlusion model of ischemic stroke, NB migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.
Topics: Animals; Choroid Plexus; Neurogenesis; Mice; Lateral Ventricles; Neural Stem Cells; Stroke; Male; Cell Movement; Cerebral Ventricles
PubMed: 38954546
DOI: 10.1073/pnas.2400213121 -
Proceedings of the National Academy of... Jul 2024The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical...
The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.
Topics: Animals; Mice; Hemodynamics; Pia Mater; Connectome; Cerebrovascular Circulation; Brain; Skull; Stroke; Male; Mice, Inbred C57BL
PubMed: 38954543
DOI: 10.1073/pnas.2402624121 -
Angewandte Chemie (International Ed. in... Jul 2024Efficient occlusion of particulate additives into a single crystal has garnered an ever-increasing attention in materials science because it offers a counter-intuitive...
Efficient occlusion of particulate additives into a single crystal has garnered an ever-increasing attention in materials science because it offers a counter-intuitive yet powerful platform to make crystalline nanocomposite materials with emerging properties. However, precisely controlling the spatial distribution of the guest additives within a host crystal remains highly challenging. We herein demonstrate a unique, straightforward method to engineer the spatial distribution of copolymer nanoparticles within calcite (CaCO3) single crystals by judiciously adjusting initial [Ca2+] concentration used for the calcite precipitation. More specifically, polymerization-induced self-assembly is employed to synthesize well-defined and highly anionic poly(3-sulfopropyl methacrylate potassium)41-block-poly(benzyl methacrylate)500 [PSPMA41-PBzMA500] diblock copolymer nanoparticles, which are subsequently used as model additives during the growth of calcite crystals. Impressively, such guest nanoparticles are preferentially occluded into specific regions of calcite depending on the initial [Ca2+] concentration. These unprecedented phenomena are most probably caused by dynamic change in electrostatic interaction between Ca2+ ions and PSPMA41 chains based on systematic investigations. This study not only showcases a significant advancement in controlling the spatial distribution of guest nanoparticles within host crystals, enabling the internal structure of composite crystals to be rationally tailored via a spatioselective occlusion strategy, but also provides new insights into biomineralization.
PubMed: 38954489
DOI: 10.1002/anie.202410908 -
Applied Biochemistry and Biotechnology Jul 2024The purpose of this investigation was to evaluate the efficacy of ultrasonic subgingival curettage in conjunction with antibacterial polypeptide periodontal gel in the...
Effect of Ultrasonic Cleaning Combined with Antibacterial Polypeptide Periodontal Gel on Inflammatory Reaction and Incidence of Adverse Reactions in Patients with Chronic Gingivitis.
The purpose of this investigation was to evaluate the efficacy of ultrasonic subgingival curettage in conjunction with antibacterial polypeptide periodontal gel in the management of chronic periodontitis of moderate to severe severity. Methods included dividing 500 hospitalised patients with moderate to severe chronic periodontitis evenly between an observation group and a control group. Subgingival ultrasonic curettage was performed on the placebo group. The non-treatment group received ultrasonic subgingival curettage and a periodontal gel rinse containing polypeptides. Results were compared before and after treatment in terms of the periodontal index, inflammation in the gingival crevicular fluid, and occlusal and masticatory efficiency. Both groups saw significant reductions in occlusal duration and occlusal force balance after treatment compared to pre-treatment levels, though the observation group saw a more dramatic decrease in these indices than the control group with P ≤ 0.05. The treatment and observation groups both saw significant reductions in the masticatory efficiency standard deviation afterward, but the index in the observation group was significantly lower than that of the control group with P ≤ 0.05.The authors claim that moderate to severe chronic periodontitis can be effectively treated with a combination of polypeptide periodontal gel and ultrasonic subgingival curettage. Substantial decreases from pre-treatment levels for both groups, with the Observation Group's index being significantly lower than the Control Group's index (P ≤ 0.05). It is possible that this treatment will help reduce inflammation and improve your periodontal health. Biting strength and occlusion stability can both be improved at the same time to help patients improve their chewing efficiency. Therefore, this method can be used securely in real-world patient care settings.
PubMed: 38954328
DOI: 10.1007/s12010-024-04928-0