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Fibrous networks constructed from high aspect ratio protein building blocks are ubiquitous in nature. Despite this ubiquity, the functional advantage of such building blocks over globular proteins is not understood. To answer this question, we engineered hydrogel network building blocks with varying numbers of protein L domains to control the aspect ratio. The mechanical and structural properties of photochemically crosslinked protein L networks were then characterised using shear rheology and small angle neutron scattering. We show that aspect ratio is a crucial property that defines network architecture and mechanics, by shifting the formation from translationally diffusion dominated to rotationally diffusion dominated. Additionally, we demonstrate that a similar transition is observed in the model living system: fibrin blood clot networks. The functional advantages of this transition are increased mechanical strength and the rapid assembly of homogenous networks above a critical protein concentration, crucial for in vivo biological processes such as blood clotting. In addition, manipulating aspect ratio also provides a parameter in the design of future bio-mimetic and bio-inspired materials. Fibrous networks constructed from high aspect ratio protein building blocks are ubiquitous in nature, but the functional advantage of such building blocks over globular proteins is not understood. Here, using shear rheology and small-angle neutron scattering, the authors characterise the mechanical and structural properties of photochemically crosslinked protein L and fibrin networks and show that aspect ratio is a crucial property that defines network architecture and mechanics. [ABSTRACT FROM AUTHOR]

In recent years, several biomarkers have been found to be associated with deep vein thrombosis (DVT). D-dimer is a degradation product of a cross-linked fibrin blood clot and has a negative value in the diagnosis of DVT. Prothrombin fragment 1 + 2 (p F1 + 2) is a non-thrombotic polypeptide that is cleaved from Prothrombin during its conversion to thrombin. The study aims to evaluate the D-dimer and to evaluate Prothrombin fragment 1 + 2 in urine and plasma in clinically suspected DVT patients. This study comprised of 30 patients who are clinically suspected cases of deep vein thrombosis, carried out from July 2018 to May 2020 in the Department of General Surgery, IMS BHU, Varanasi. In our study, D-dimer and plasma F1 + 2 both showed comparable results in patients of venous thromboembolism (VTE). Proximal DVT tended to have higher levels of D-dimer and had significantly higher levels of F1 + 2 than patients with distal DVT. In our study, a positive correlation was found between D-dimer and plasma F1 + 2 (r = 0.588 and p-value 0.006) in DVT-positive patients. There is no correlation between plasma D-dimer and urine F1 + 2 (r = − 0.0.07 and p-value 0.769) In conclusion, Prothrombin F1 + 2 is an important marker raised in patients with DVT. [ABSTRACT FROM AUTHOR]

MiRNAs are small RNA strands that are managed following transcription and are of substantial importance in blood vessel formation. It is essential to oversee the growth, differentiation, death, movement and construction of tubes by angiogenesis-affiliated cells. If miRNAs are not correctly regulated in regard to angiogenesis, it can deteriorate the health and lead to various illnesses, which include cancer, cardiovascular disorder, critical limb ischemia, Crohn's disease, ocular diseases, diabetic microvascular complications, and more. Consequently, it is vital to understand the crucial part that miRNAs play in the development of blood vessels, so we can develop reliable treatment plans for vascular diseases. This write-up will assess the critical role of miR-21/exosomal miR-21 in managing angiogenesis associated with bone growth, wound recovery, and other pathological conditions like tumor growth, ocular illnesses, diabetes, and other diseases connected to formation of blood vessels. Previous investigations have demonstrated that miR-21 is present at higher amounts in certain cancerous cells, and it influences a multitude of genes that moderate the increased creation of blood vessels. Furthermore, studies demonstrated that exosomal miR-21 has the capacity to interact with endothelial cells to foster tumor angiogenesis. For that reason, this review explains the critical importance of miR-21/exosomal miR-21 in managing both healthy and diseased states of angiogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Infections with coagulase negative staphylococcal species (CoNS) are a major cause of mortality and morbidity in joint and heart valve replacement procedures, largely due to biofilm formation. Cells within biofilms have higher rates of antibiotic resistance than their planktonic counterparts; consequently, novel mechanisms are needed to combat these infections. Methods: To enhance antibiotic delivery and penetration, this innovative study involved treating CoNS biofilms with murine blood clots impregnated with antibiotics. We then investigated the impact of this treatment on biofilm density, metabolism, and architecture. Results: Our pilot study demonstrates that this method of antibiotic delivery results in improved biofilm clearance, relative to conventional exposure methods. Discussion: Our results demonstrate that blood clot exposure has an intrinsic impact on biofilm density and potentially reduces colonization, warrenting further investigation into the mechanism. [ABSTRACT FROM AUTHOR]

Background: Jugular foramen syndrome (JFS) is a rare condition characterized by the compression or impairment of one or more terminal cranial nerves passing through the jugular foramen. Although malignancies are the primary cause of JFS. Methods: In this report, we present the first documented case of JFS caused by acute otitis media in an adult patient. Results: A 74-year-old woman presented with ear pain, hoarseness, dysphagia, dizziness, tinnitus, and hearing loss. A physical examination revealed a reddish-bulging tympanic membrane, left-sided hearing loss, right uvula deviation, and cranial nerve palsies affecting the ninth and tenth nerves. Imaging studies confirmed temporal bone inflammation, thrombosis of the sigmoid sinus extending into the internal jugular vein, and signs of thrombophlebitis of the jugular vein. The patient underwent a cortical mastoidectomy, sigmoid sinus decompression, and ventilation tube insertion, along with antibiotic, steroid, and anticoagulant therapy. Postoperatively, the patient's condition improved significantly. Conclusions: This case highlights the importance of considering complicated acute otitis media in the differential diagnosis of neurological abnormalities associated with JFS. A thorough evaluation of the patient's medical history and radiological imaging can assist in identifying the cause of the symptoms and guide appropriate surgical or conservative treatment. Further research is essential to gain more comprehensive insights into the pathophysiology and therapeutic interventions of JFS affecting the ears. [ABSTRACT FROM AUTHOR]

Background: Rearranged during transfection (RET) fusions represent a distinct molecular subset of non-small cell lung cancer (NSCLC) with targeted therapeutic potential. Selpercatinib, a highly selective RET inhibitor, has demonstrated efficacy in various solid tumors harboring RET alterations. Here, we present a case highlighting the use and clinical outcomes of selpercatinib in a patient diagnosed with advanced lung adenocarcinoma harboring a RET fusion. Case presentation: A 59-year-old woman with a history of stage IV lung adenocarcinoma harboring a KIF5B-RET fusion presented with disease progression following first-line chemo-immunotherapy. Selpercatinib was initiated as a targeted therapy, leading to a notable radiographic response and clinical improvement. The patient experienced a significant reduction in tumor burden and reported improved symptom control, with no significant adverse effects during the 21-month follow-up period. Conclusions: This case highlights the efficacy and tolerability of selpercatinib in treating advanced lung adenocarcinoma with a RET fusion. The observed clinical response supports the early use of selpercatinib as a targeted therapy for RET fusion-positive NSCLC, including in patients with compromised general and respiratory conditions, especially in cases refractory to conventional treatments. Long-term follow-up studies are warranted to validate these findings and assess the durability of responses. [ABSTRACT FROM AUTHOR]

Background: Anemia is considered a risk factor for cardiovascular disease. However, there is little evidence regarding the relationship between hemoglobin (HB) and cerebral infarction after revascularization in patients with moyamoya disease (MMD). This study aimed to explore the relationship between postoperative cerebral infarction and HB in patients with MMD and to establish a predictive model. Methods: Demographic information and different HB levels (the preoperative and postoperative HB, highest and lowest HB, and mean HB during hospitalization) of 112 patients with MMD were collected, of which 11 had cerebral infarction after revascularization. Results: In the binomial logistic regression analysis, low HB levels were an independent risk factor for cerebral infarction after revascularization, which also led to a worse long-term prognosis in patients with MMD. The risk factors, including Pre-HB, Post-HB, type of MMD, and hypertension (HTN), were incorporated into the receiver operating characteristic curve, which yielded an area under the curve (AUC) of 0.83. Conclusion: The prediction model was visualized using a nomogram, and a clinical decision curve was drawn to evaluate the net benefit of clinical decisions. [ABSTRACT FROM AUTHOR]

Cardiac masses are complex clinical conditions that frequently pose diagnostic challenges in cardiology practice. These masses can form within heart chambers or near the pericardium and are generally categorized as either non-neoplastic or neoplastic. These latter are further classified into benign and malignant (primary and secondary or metastatic). Diagnosing these conditions often requires a multiparametric approach that includes both clinical features, such as the patient's and associated clinical conditions, and multimodality imaging. However, histological examination of the resected specimen is often necessary to ascertain the nature of the mass. Given their heterogeneity and the rarity of many cardiac masses, there are no guidelines or consensus on the best diagnostic approach. Modern imaging protocols must be tailored to the specific clinical issues and patient characteristics, given the rapid advancements in technology. Thus, it is imperative to use a multimodality approach, combining different imaging techniques and multidisciplinary teamwork. Hereby, we propose a practical algorithm for evaluating cardiac lesions using a step-by-step implementation of multimodal imaging. Ultimately, the goal is to tailor the most suitable imaging technique to the patient's needs. [ABSTRACT FROM AUTHOR]

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Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the role of oxylipins and lipid mediators in Pulmonary Embolism (PE), a serious cardiovascular condition associated with high morbidity and mortality rates. Methods: A total of 6,365 hospitalized patients with thrombosis and 200 healthy individuals were recruited as the control group from 2015 to 2023. Thrombus type, coagulation, and lipid-related parameters were statistically analysed. Additionally, lipidomic characteristics of serum samples from the PE and control groups were examined via LC-MS/MS for the first time. Results: Among the 6,365 hospitalized patients with thrombosis, 72.1% (4,587/6,365) had venous thromboembolism (VTE). Within the VTE group, the incidence of PE was 12.1% (555/4,587). In comparison to the healthy control (HC) group, the PE group exhibited significant elevations in coagulation-related parameters, such as factor VIII (F VIII) and von Willebrand factor (vWF) activities, while antithrombin III (AT III) and factor XII (F XII) activities were notably reduced. Lipid-related parameters, including serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (apoA), were significant reductions in PE patients (P < 0.0001), with areas under the curve (AUCs) exceeding 0.9. LC-MS/MS analysis of serum samples revealed 118 oxidized lipid metabolites. Compared to the HC group, the PE group exhibited 10 upregulated oxidized lipid metabolites, with the most significant difference observed in 20-hydroxyPGF2α derived from arachidonic acid (ARA). The study identified upregulated oxidized lipid metabolites primarily linked to the ARA metabolism signalling pathway. Conclusion: This research indicates a notable correlation between lipid metabolism and the occurrence and development of PE. Specifically, upregulation of the arachidonic acid metabolism signalling pathway may be an important pathogenic factor for PE, and 20-hydroxyPGF2α derived from ARA has potential as a biomarker for PE disease. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, there was increased interest in the issue of thrombotic complications of acute respiratory infections. Clinical reports and pathological studies have revealed that thrombus formation in COVID-19 may involve the venous and arterial vasculature. As thrombotic complications of infectious respiratory diseases are increasingly considered in the context of COVID-19, the fact that thrombosis in lung diseases of viral and bacterial etiology was described long before the pandemic is overlooked. Pre-pandemic studies show that bacterial and viral respiratory infections are associated with an increased risk of thrombotic complications such as myocardial infarction, ischemic stroke, pulmonary embolism, and other critical illnesses caused by arterial and venous thrombosis. This narrative review article aims to summarize the current evidence regarding thrombotic complications and their pathogenesis in acute lower respiratory tract infections. [ABSTRACT FROM AUTHOR]

The contact pathway of blood clotting has received intense interest in recent years as studies have linked it to thrombosis, inflammation, and innate immunity. Because the contact pathway plays little to no role in normal hemostasis, it has emerged as a potential target for safer thromboprotection, relative to currently approved antithrombotic drugs which all target the final common pathway of blood clotting. Research since the mid-2000s has identified polyphosphate, DNA, and RNA as important triggers of the contact pathway with roles in thrombosis, although these molecules also modulate blood clotting and inflammation via mechanisms other than the contact pathway of the clotting cascade. The most significant source of extracellular DNA in many disease settings is in the form of neutrophil extracellular traps (NETs), which have been shown to contribute to incidence and severity of thrombosis. This review summarizes known roles of extracellular polyphosphate and nucleic acids in thrombosis, with an emphasis on novel agents under current development that target the prothrombotic activities of polyphosphate and NETs. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration is a progressive, blinding macular disease that has become a burden both in healthcare systems and the global economy. The vascular endothelial growth factor (VEGF) is the main agent involved in the pathogenic process of the disease. The main goal of the age-related macular degeneration treatment is to maintain and improve visual acuity by injecting intravitreal anti-VEGF agents in either a reactive or proactive manner. Subretinal and intraretinal fluids are the main biomarkers that should be considered when managing the frequency of the therapy. This review discusses both functional and morphological treatment criteria according to current recommendations as opposed to real-life situations encountered during day-to-day clinical practice and highlights situations in which the benefits of continuing therapy are arguable in terms of improving patients' quality of life. Optimizing the treatment regimen represents an important aim of current clinical ophthalmological practice, as age-related macular degeneration patients usually have a long follow-up period. [ABSTRACT FROM AUTHOR]

A hallmark of angiogenesis is the sprouting of endothelial cells. To replicate this event in vitro, biomaterial approaches can play an essential role in promoting cell migration. To study the capacity of a scaffold of fibrin (fibrinogen:thrombin mix) to support the movement of the endothelial cells, the migration area of spheroids formed with the HULEC cell line was measured. The cells were first allowed to form a spheroid using the hanging drop technique before being encapsulated in the fibrin gel. The cells' migration area was then measured after two days of embedding in the fibrin gel. Various conditions affecting fibrin gel polymerization, such as different concentrations of fibrinogen and thrombin, were evaluated alongside rheology, porosity, and fiber thickness analysis to understand how these factors influenced cell behavior within the composite biomaterial. Data point toward thrombin's role in governing fibrin gel polymerization; higher concentrations result in less rigid gels (loss tangent between 0.07 and 0.034) and increased cell migration (maximum concentration tested: 5 U/mL). The herein presented method allows for a more precise determination of the crosslinking conditions of fibrin gel that can be used to stimulate angiogenic sprouting. [ABSTRACT FROM AUTHOR]

Background and Objectives: Parkinson's disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms. In any disease with underlying inflammation, immune system mediators called cytokines are released, leading to a procoagulant state. Our aim was to study the coagulation parameters in patients with PD and find their correlation with disease duration and antiparkinsonian drugs. Methods: This cross-sectional study was conducted between January 2021 and December 2021 in a tertiary care center. Sixty-eight patients with PD were subcategorized based on disease duration (<5 and ≥5 years), number of antiparkinsonian drugs (one drug and ≥2 drugs), and levodopa equivalent daily dose (LEDD; <350 and ≥350 mg). Hemoglobin (Hb), prothrombin time (PT), fibrinogen, bleeding time, and platelet aggregation study with adenosine diphosphate and collagen were assessed. Results: In our cohort of 68 patients, 53 were men and 15 were women. Mean disease duration was 5.97 ± 4.37 years. Hb was negatively associated with LEDD (P = 0.012) and duration of the disease (P = 0.02). Similarly, PT was negatively associated with disease duration (P = 0.041) and number of antiparkinsonian drugs (P = 0.03). LEDD showed a positive association with collagen-induced platelet aggregation (P = 0.03). Conclusions: In our study, patients using multiple antiparkinsonian drugs and higher LEDD were observed to have a prothrombotic state. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Studies aiming to understand the effects of storage on whole blood (WB) clotting often rely on characterizing coagulation under static conditions. Minimal work has explored the effects of physiologic shear on clot formation and thrombolysis utilizing fractionated and reconstituted whole blood (rWB) products. WB was fractionated into platelet‐free plasma, packed red blood cells, and platelets storing each component under its ideal conditions—including platelet cryopreservation. Recombination at their native ratios was accomplished over 91 days of storage and clotting/thrombolysis was analyzed utilizing thromboelastography and Chandler loop. rWB preserved clot strength through 91 days with minimal deviation from baseline, in contrast to WB stored at 4°C which experienced a significant decline by storage Day‐42. Clot formation under shear for both rWB and WB led to increased clot mass through storage. No significant deviation from baseline was appreciated until Day 70 of storage in rWB. Increasing degrees of thrombolysis were seen in both groups, with rWB significantly deviating from baseline at Day 70. No significant changes in overall clot architecture occurred throughout storage and recombination. This fractionation and recombination protocol serves as a method to further develop reproducible in vitro clot analogs for preclinical thrombolytic therapy screening. [ABSTRACT FROM AUTHOR]

Simple Summary: Infective endocarditis represents a rare, acquired condition in animals, but also in humans, that typically involves one of the heart valves and mainly affecting the mitral and aortic valves in dogs. This report describes the clinical signs, the diagnostic approach and the postmortem investigations of a case confirmed with infective endocarditis at the level of the aortic valve but also the presence of a main consequence of the disease, represented by the development of paravalvular abscesses and subsequent fistulous tracts between heart chambers. Infective endocarditis is a severe but rarely diagnosed disease, characterized by the presence of bacterial infection at the level of the cardiac valves. Although the incidence of the disease is very low, the consequences are severe and the prognosis is very poor, outlining a high mortality rate among cases. The present report highlights the case of a 7-year-old dog presented with abrupt changes in the respiratory pattern, obtunded and in lateral recumbency. The physical examination of the patient revealed fever and a IV/VI systolic heart murmur, with the point of maximal intensity on the left hemithorax. Echocardiography identified hyperechoic and cavitary changes beneath the aortic valves and a retrograde turbulent jet originating in the left ventricle outflow tract communicating with the left atrium through a rupture in the aortomitral intervalvular wall. Because of very unstable hemodynamic changes, the dog suddenly died despite the initiation of intensive care supportive treatment, and the postmortem evaluation of the heart confirms the suspicion of infective aortic endocarditis with the development of a paravalvular abscess and an aorto-left atrial fistula. [ABSTRACT FROM AUTHOR]

Enolase is a 47 kDa enzyme that functions within the glycolysis and gluconeogenesis pathways involved in the reversible conversion of D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP). However, in the context of host-pathogen interactions, enolase from different species of parasites, fungi and bacteria have been shown to contribute to adhesion processes by binding to proteins of the host extracellular matrix (ECM), such as fibronectin (FN) or laminin (LM). In addition, enolase is a plasminogen (PLG)-binding protein and induces its activation to plasmin, the main protease of the host fibrinolytic system. These secondary 'moonlighting' functions of enolase are suggested to facilitate pathogen migration through host tissues. This study aims to uncover the moonlighting role of enolase from the parasite Fasciola hepatica, shedding light on its relevance to host-parasite interactions in fasciolosis, a global zoonotic disease of increasing concern. A purified recombinant form of F. hepatica enolase (rFhENO), functioning as an active homodimeric glycolytic enzyme of ~94 kDa, was successfully obtained, fulfilling its canonical role. Immunoblotting studies on adult worm extracts showed that the enzyme is present in the tegument and the excretory/secretory products of the parasite, which supports its key role at the host-parasite interface. Confocal immunolocalisation studies of the protein in newly excysted juveniles and adult worms also localised its expression within the parasite tegument. Finally, we showed by ELISA that rFhENO can act as a parasitic adhesin by binding host LM, but not FN. rFhENO also binds PLG and enhances its conversion to plasmin in the presence of the tissue-type and urokinase-type PLG activators (t-PA and u-PA). This moonlighting adhesion-like function of the glycolytic protein enolase could contribute to the mechanisms by which F. hepatica efficiently invades and migrates within its host and encourages further research efforts that are designed to impediment this function by vaccination or drug design. Author summary: Fasciola hepatica is a parasitic worm causing fasciolosis, primarily affecting herbivorous mammals and posing a significant veterinary problem. Furthermore, it is a zoonosis, meaning it can be transmitted to humans. F. hepatica enters the definitive host through ingestion of contaminated aquatic plants, migrating through the intestine to settle in the liver bile ducts, where it matures into the adult stage. To migrate, it utilizes various invasion strategies, including the use of multifunctional proteins, known as 'moonlighting'. In this study, we produced and molecularly characterized the parasitic enzyme enolase as a moonlighting protein to understand F. hepatica invasion mechanisms. We produced recombinant enolase with glycolytic activity, its canonical function in parasite energy production. Additionally, we localised this enzyme in the parasite's tegument, in direct contact with the host, and studied its ability to elicit an immune response early in ovine infection. Finally, we demonstrated the ability of enolase to interact with the extracellular matrix and the host's fibrinolysis, a proteolytic system responsible for dissolving blood clots. These secondary functions of F. hepatica enolase, described here for the first time, along with its localisation, suggest this protein as an interesting antigen for fasciolosis control. [ABSTRACT FROM AUTHOR]

Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the "two-way" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications. Developing porous hemostatic sponges remains challenging. Here, authors proposed a temperature-assisted secondary network compaction strategy following the phase separation induced primary compaction to fabricate the superporous chitosan sponges. [ABSTRACT FROM AUTHOR]

Numerous scientific and medical domains have been revolutionized by nanotechnology, opening up unprecedented opportunities for healthcare applications. Among these developments, the creation of nanorobots for artificial blood components is a novel field of research that seeks to overcome the constraints of conventional pharmacological therapy. This review article provides a comprehensive overview of the nanorobotic artificial blood components and their therapeutic uses. The article begins by outlining the core concepts of nanotechnology and nanorobotic systems, emphasizing their design and control methods. It then delves into various types of nanorobotic artificial blood components, such as oxygen transporters (artificial RBCs), clotting agents (artificial platelets), and immune modulators (artificial WBCs). It goes into detail about their properties, functioning, and capabilities, which allow them to replicate the physiological activities of actual blood components. The article also assesses the clinical uses of artificial blood components in a variety of medical circumstances. It highlights their potential value in the management of certain blood-related diseases. [ABSTRACT FROM AUTHOR]

Cell migration is fundamental to both development and adult physiology, including gastrulation, brain development, angiogenesis, wound healing, bone remodeling, tissue homeostasis, and the immune response. Additionally, misguided cellular migration is implicated in disease pathologies such as cancer metastasis and fibrosis. The microenvironment influences cell migration modes such as mesenchymal, amoeboid, lobopodial, and collective, and these are governed through local signaling by affecting the gene expression and epigenetic alteration of migration-related genes. Plasticity in switching between migration modes is essential for key cellular processes across various contexts. Understanding the mechanisms of cell migration modes and its plasticity is essential for unraveling the complexities of this process and revealing its implications in physiological and pathological contexts. This review focuses on different modes of cell migration, including their aberrant migration in disease pathologies and how they can be therapeutically targeted in disease conditions such as cancer. [ABSTRACT FROM AUTHOR]

Background: Pseudothrombocytopenia (PTCP) can be caused by anticoagulants or pre-analytical issues. The authors present a case of PTCP attributed to pre-analytical issues in a 68-year-old male patient. Methods: The platelet count results were obtained using both the impedance and fluorescence channels of Sysmex XN-10. The blood film was scanned using both Cellavision DM96 and a microscope. Results: The flag for PLT-Clumps and the scattergram from the PLT-F channel indicated the presence of platelet aggregation. Fibrin could be observed at the feathered end of the blood film. A diagnosis of PTCP resulting from pre-analytical issues was made. Conclusions: The presence of fibrin in a blood film is a critical indicator for diagnosing PTCP due to pre-analytical issues. [ABSTRACT FROM AUTHOR]

Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS‐R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS‐R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS‐R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS‐R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS. [ABSTRACT FROM AUTHOR]

Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes. This cell-cell communication is necessary to coordinate the immune response to lower respiratory tract infection. Recent discoveries identify an important role for the microtubule-associated protein tau that is expressed in lung capillary endothelia in the host-pathogen interaction. This endothelial tau stabilizes microtubules necessary for barrier integrity, yet infection drives production of cytotoxic tau variants that are released into the airways and circulation, where they contribute to end-organ dysfunction. Similarly, beta-amyloid is produced during infection. Beta-amyloid has antimicrobial activity, but during infection it can acquire cytotoxic activity that is deleterious to the host. The production and function of these cytotoxic tau and amyloid variants are the subject of this review. Lung-derived cytotoxic tau and amyloid variants are a recently discovered mechanism of end-organ dysfunction, including neurocognitive dysfunction, during and in the aftermath of infection. [ABSTRACT FROM AUTHOR]

Background: To evaluate the outcomes of intravitreal faricimab (IVF) for refractory neovascular age-related macular degeneration (nAMD) and investigate the impact of baseline optical coherence tomography, biomarkers for total IVF injections are needed. Methods: A retrospective analysis of 33 eyes of patients who completed one year (52 W) of treatment with IVF. The eyes received four IVF injections (6 mg/0.05 mL) as the upload phase. Thereafter, the treatment interval was extended to 8 or 12 weeks if disease activity was not recorded. The outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal fluid distribution. Results: A total of 33 eyes were included. CMT decreased significantly at 52 W (p < 0.01). BCVA and SFCT did not change significantly at 52 W (p > 0.05). The number of eyes with subretinal fluid decreased significantly at 52 W (p < 0.01). Complete fluid resolution was achieved in 20 eyes (60%). The total number of injections was significantly negatively correlated with the presence of hyperreflective dots at baseline (HRDs, p < 0.01) and SFCT at baseline (p < 0.01). Conclusions: IVF led to a significant reduction in CMT with stabilization of BCVA. The total number of injections was lower in eyes with HRDs and increased SFCT at baseline. This might provide clues regarding response to IVF for future studies. [ABSTRACT FROM AUTHOR]

The maintenance of phosphate homeostasis serves as a foundation for energy metabolism and signal transduction processes in all living organisms. Inositol pyrophosphates (PP-InsPs), composed of an inositol ring decorated with monophosphate and diphosphate moieties, and inorganic polyphosphate (polyP), chains of orthophosphate residues linked by phosphoanhydride bonds, are energy-rich biomolecules that play critical roles in phosphate homeostasis. There is a complex interplay between these two phosphaterich molecules, and they share an interdependent relationship with cellular adenosine triphosphate (ATP) and inorganic phosphate (Pi). In eukaryotes, the enzymes involved in PP-InsP synthesis show some degree of conservation across species, whereas distinct enzymology exists for polyP synthesis among different organisms. In fact, the mechanism of polyP synthesis in metazoans, including mammals, is still unclear. Early studies on PPInsP and polyP synthesis were conducted in the slime mould Dictyostelium discoideum, but it is in the budding yeast Saccharomyces cerevisiae that a clear understanding of the interplay between polyP, PP-InsPs, and Pi homeostasis has now been established. Recent research has shed more light on the influence of PP-InsPs on polyP in mammals, and the regulation of both these molecules by cellular ATP and Pi levels. In this review we will discuss the cross-talk between PP-InsPs, polyP, ATP, and Pi in the context of budding yeast, slime mould, and mammals. We will also highlight the similarities and differences in the relationship between these phosphate-rich biomolecules among this group of organisms. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known 'risk factors' for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications. [ABSTRACT FROM AUTHOR]