Effects of Surgery on Hemodynamics and Postoperative Delirium in Stanford Type A Aortic Dissection.

Objective: To investigate the impact of surgical intervention on hemodynamic parameters and postoperative delirium in Stanford Type A aortic dissection patients.

Methods: A retrospective analysis was conducted on 139 patients who underwent surgery for Stanford Type A aortic dissection from February 2022 to February 2024. Hemodynamic parameters, including maximum ascending aortic diameter (MAAD), left ventricular end-diastolic diameter (LVEDd), and ejection fraction (LVEF), were compared pre- and post-surgery.

A Three-Monoclonal Antibody Combination Potently Neutralizes BoNT/G Toxin in Mice.

Equine-derived antitoxin (BAT) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated.

Multicolor fluorescence activated cell sorting to generate humanized monoclonal antibody binding seven subtypes of BoNT/F.

Generating specific monoclonal antibodies (mAbs) that neutralize multiple antigen variants is challenging. Here, we present a strategy to generate mAbs that bind seven subtypes of botulinum neurotoxin serotype F (BoNT/F) that differ from each other in amino acid sequence by up to 36%. Previously, we identified 28H4, a mouse mAb with poor cross-reactivity to BoNT/F1, F3, F4, and F6 and with no detectable binding to BoNT/F2, F5, or F7.

The Novel Clostridial Neurotoxin Produced by Strain IBCA10-7060 Is Immunologically Equivalent to BoNT/HA.

Background: Botulinum neurotoxins (BoNTs) comprise seven agreed-on serotypes, A through G. In 2014, a novel chimeric neurotoxin produced by clostridial strain IBCA10-7060 was reported as BoNT/H, with subsequent names of BoNT/FA or BoNT/HA based on sequence homology of the N-terminus to BoNT/F, the C-terminus to BoNT/A and neutralization studies. The purpose of this study was to define the immunologic identity of the novel BoNT.

Patient compliance with an anticoagulation management system based on a smartphone application.

We developed a novel anticoagulation management system (Anticlot Assistant) based on a smartphone application (App). This study was performed to evaluate patient compliance with Anticlot Assistant. This prospective case series study involved patients receiving warfarin therapy.

A three monoclonal antibody combination potently neutralizes multiple botulinum neurotoxin serotype F subtypes.

Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes.

Delayed protective effect of telmisartan on lung ischemia/reperfusion injury in valve replacement operations.

The present study aimed to investigate the delayed protective effect of telmisartan on lung ischemic/reperfusion injury in patients undergoing heart valve replacement operations. In total, 180 patients diagnosed with rheumatic valve diseases were randomly divided into the telmisartan (T), captopril (C) and placebo (P) groups. In the telmisartan group, the patients were pretreated with telmisartan (1 mg/kg/day), at the time period 96-48 h before the operation, whereas in the C group, the patients were treated with captopril (1 mg/kg/day) at the time period 96-48 h prior to the operation control group.

Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H.

Background: Only Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed.

Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5.

KIT is a cell surface tyrosine kinase receptor whose ligand stem cell factor (SCF) triggers homodimerization and activation of downstream effector pathways involved in cell survival, proliferation, homing, or differentiation. KIT-activating mutations are major oncogenic drivers in subsets of acute myeloid leukemia (AML), in mast cell leukemia, and in gastrointestinal stromal tumors (GIST). The overexpression of SCF and/or wild-type (WT) KIT is also observed in a number of cancers, including 50% of AML and small cell lung cancer.

Monoclonal Antibodies that Inhibit the Proteolytic Activity of Botulinum Neurotoxin Serotype/B.

Existing antibodies (Abs) used to treat botulism cannot enter the cytosol of neurons and bind to botulinum neurotoxin (BoNT) at its site of action, and thus cannot reverse paralysis. However, Abs targeting the proteolytic domain of the toxin could inhibit the proteolytic activity of the toxin intracellularly and potentially reverse intoxication, if they could be delivered intracellularly. As such, antibodies that neutralize toxin activity could serve as potent inhibitory cargos for therapeutic antitoxins against botulism.

Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.

The paralytic disease botulism is caused by botulinum neurotoxins (BoNT), multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC) of BoNT serotype A (BoNT/A) was targeted for generation of monoclonal antibodies (mAbs) that could reverse paralysis resulting from intoxication by BoNT/A.

Development of an ELISA microarray assay for the sensitive and simultaneous detection of ten biodefense toxins.

Plant and microbial toxins are considered bioterrorism threat agents because of their extreme toxicity and/or ease of availability. Additionally, some of these toxins are increasingly responsible for accidental food poisonings. The current study utilized an ELISA-based protein antibody microarray for the multiplexed detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F, ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in buffer and complex biological matrices.

Endothelial progenitor cell transplantation improves long-term stroke outcome in mice.

Objective: Endothelial progenitor cells (EPCs) play an important role in tissue repairing and regeneration in ischemic organs, including the brain. However, the cause of EPC migration and the function of EPCs after ischemia are unclear. In this study, we demonstrated the effects of EPCs on ischemic brain injury in a mouse model of transient middle cerebral artery occlusion (tMCAO).

A single-domain llama antibody potently inhibits the enzymatic activity of botulinum neurotoxin by binding to the non-catalytic alpha-exosite binding region.

Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc).

Postischemic IGF-1 gene transfer promotes neurovascular regeneration after experimental stroke.

Promoting neural regeneration after cerebral infarction has emerged as a potential approach for the treatment of stroke. Insulin-like growth factor 1 (IGF-1) possesses both neurotrophic and angiogenic properties. The aim of this study was to determine whether postischemic gene transfer of IGF-1 enhances neurovascular regeneration in a mouse model of permanent focal cerebral ischemia.

Sexual reproduction in higher plants I: fertilization and the initiation of zygotic program.

Sexual plant reproduction is a critical developmental step in the life cycle of higher plants, to allow maternal and paternal genes to be transmitted in a highly regulated manner to the next generation. During evolution, a whole set of signal transduction machinery is developed by plants to ensure an error-free recognition between male and female gametes and initiation of zygotic program. In the past few years, the molecular machineries underlying this biological process have been elucidated, particularly on the importance of synergid cells in pollen tube guidance, the Ca(++) spike as the immediate response of fertilization and the epigenetic regulation of parental gene expressions in early zygotic embryogenesis.

Del-1 gene transfer induces cerebral angiogenesis in mice.

Developmental endothelial locus-1 (Del-1) is a novel angiomatrix protein that has been shown to stimulate a potent angiogenic response and promote functional recovery in hind-limb and cardiac ischemia in animal models; however, its impact on cerebral angiogenesis is unknown. In this study, we investigated whether Del-1 overexpression via gene transfer induces cerebral angiogenesis in a murine model, and examined Del-1 expression after ischemic stroke. Cerebral Del-1 overexpression was achieved with AAV (adeno-associated virus) transduction system via stereotactic injection.

Overexpression of netrin-1 induces neovascularization in the adult mouse brain.

Netrin-1 is a critical molecule for axonal pathfinding during embryo development, and because of its structural homology to the endothelial mitogens, it may share its effects on vascular network formation. Using an adeno-associated viral netrin-1 vector (AAV-NT-1) gene transfer, we demonstrated that netrin-1 was able to stimulate the proliferation and migration of human cerebral endothelial cells (HCECs) and human aortic smooth muscle cells (HASMCs) compared with the control (P<0.05), and could also promote HCEC tube formation on matrigel (P<0.

Insulin growth factor-1 gene transfer enhances neurovascular remodeling and improves long-term stroke outcome in mice.

Background And Purpose: Insulin-like growth factor I (IGF-1) is a pleiotropic growth factor that has been demonstrated to protect against acute ischemic brain injury. Whether IGF-1 improves long-term functional outcome after ischemic stroke is not known. The aim of this study is to examine whether IGF-1 overexpression through adeno-associated virus (AAV) -mediated gene transfer enhances neurovascular remodeling and improves functional outcome in a mouse model of focal cerebral ischemia.

Therapeutic angiogenesis for brain ischemia: a brief review.

In the normal mature brain, blood vessel formation is tightly downregulated. However, pathologic processes such as ischemia can induce cerebral vascular regeneration. Angiogenesis is one of the major styles of new vessel formation.

Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro.

Circulating blood endothelial progenitor cells (EPCs) contribute to postnatal vasculogenesis, providing a novel therapeutic target for vascular diseases. However, the molecular mechanism of EPC-induced vasculogenesis is unknown. Interleukin-6 plays multiple functions in angiogenesis and vascular remodeling.

Neutrophil depletion decreases VEGF-induced focal angiogenesis in the mature mouse brain.

To explore the role of neutrophil-derived matrix metalloproteinases (MMPs) during angiogenesis in the brain, we hypothesized that transient neutrophil depletion attenuates the angiogenic response to focal hyperstimulation with vascular endothelial growth factor (VEGF). Brain focal angiogenesis was achieved using an adeno-associated virus delivered VEGF (AAV-VEGF) gene transfer in the mature mouse. Four groups of mice underwent AAV vector injection in the brain parenchyma: (1) AAV-LacZ; (2) AAV-VEGF; (3) AAV-VEGF plus anti-polymorphonuclear (PMN) antibody; and (4) AAV-VEGF plus serum.

Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury after focal cerebral ischemia in mice.

Background And Purpose: Exogenous delivery of vascular endothelial growth factor gene (VEGF) may provide a useful approach to the treatment of brain ischemia. We investigated the use of a hypoxia-responsive element to control VEGF expression given for neuroprotection.

Methods: Three groups (n=36) of mice received AAVH9-VEGF, AAVH9-lacZ, or saline injection.

Pretreatment with PTD-calbindin D 28k alleviates rat brain injury induced by ischemia and reperfusion.

Calcium toxicity remains the central focus of ischemic brain injury. Calcium channel antagonists have been reported to be neuroprotective in ischemic animal models but have failed in clinical trials. Rather than block the calcium channels, calbindin proteins can buffer excessive intracellular Ca2+, and as a result, maintain the calcium homeostasis.

Interleukin-6 upregulates expression of KDR and stimulates proliferation of human cerebrovascular smooth muscle cells.

Interleukin-6 (IL-6) may play multiple roles in angiogenesis and vascular remodeling. Our previous study showed that a promoter polymorphism (174G>C) in IL-6 is associated with brain arteriovenous malformation hemorrhage; tissue expression is related to genotype. In this study, we investigated the effects of IL-6 on human cerebral smooth muscle cells (HCSMCs) and smooth muscle cells isolated from brain arteriovenous malformation surgical specimens (AVM SMCs) and surgical controls (control HCSMCs--from structurally normal temporal lobe taken during surgical treatment of epilepsy patients).