Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens.
View Article and Find Full Text PDFChronic diabetic wounds represent the most common diabetes complication. Wound healing depends on scavenging reactive oxygen species (ROS), neovascularization, and controlling infection. A naturally derived gelatin-based hydrogel is biocompatible, biodegradable, does not promote inflammation, and can remove ROS, but strategies for developing a gelatin-based hydrogel currently require careful chemical modification of gelatin and time-consuming purification and post-crosslinking processing.
View Article and Find Full Text PDFMetal-polyphenol networks (MPNs) are of immense scientific interest because of their simple and rapid process to deposit on various substrates or particles with different shapes. However, there are rare reports on the effect of polyphenol molecular structure on coating efficiency and mechanism of MPNs. Herein, three typical flavonoid polyphenols, catechin (Cat), epigallocatechin (EGC) and procyanidin (PC), with the same skeleton (C6-C3-C6) but subtle distinction in molecular structure, were selected to build MPN coatings with ferric ions (Fe).
View Article and Find Full Text PDFRas plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear.
View Article and Find Full Text PDFGlioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPR/Cas9 gene-editing technology in the treatment of glioma.
View Article and Find Full Text PDFDrug Des Devel Ther
October 2022
Remimazolam is a novel short-acting γ-aminobutyric acid (GABA) receptor agonist with typical characteristics of benzodiazepine sedative drugs, nonorgan-dependent metabolism, long-term infusion without accumulation, and no injection pain. It is quite different from the other current sedative drugs and has broad prospects for application. It has been established that the metabolites of remimazolam are inactive, and the interactions with other drugs are weak with slight cardiopulmonary suppressive effects, showing good effectiveness and safety.
View Article and Find Full Text PDFPurpose: Sepsis, which is deemed as a systemic inflammation reaction syndrome in the face of infectious stimuli, is the primary cause of death in ICUs. Sepsis-induced cardiomyopathy (SIC) may derive from systemic inflammation reaction and oxidative stress. Retinoic acid (RA) is recognized by its beneficial roles in terms of the immunoresponse to infections and antioxygen actions.
View Article and Find Full Text PDFPatients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings.
View Article and Find Full Text PDFFront Cell Neurosci
June 2022
Stroke is a major public health issue, corresponding to the second cause of mortality and the first cause of severe disability. Ischemic stroke is the most common type of stroke, accounting for 87% of all strokes, where early detection and clinical intervention are well known to decrease its morbidity and mortality. However, the diagnosis of ischemic stroke has been limited to the late stages, and its therapeutic window is too narrow to provide rational and effective treatment.
View Article and Find Full Text PDFBackground: Myopathies related to Ryanodine receptor 1 (RYR1) mutation are the most common nondystrophy muscle disorder in humans. Early detection and diagnosis of RYR1 mutation-associated myopathies may lead to more timely treatment of patients, which contributes to the management and preparation for malignant hyperthermia. However, diagnosis of RYR1 mutation-associated myopathies is delayed and challenging.
View Article and Find Full Text PDFStroke, a disease with a sudden onset and high morbidity and mortality rates, is difficult to treat in the clinic. Traditional Chinese medicine has become increasingly widely used in clinical practice. Modern pharmacological studies have found that Radix Astragali has a variety of medicinal properties, i.
View Article and Find Full Text PDFBackground: MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs).
View Article and Find Full Text PDFBackground: Microglia, neuron, and vascular cells constitute a dynamic functional neurovascular unit, which exerts the crucial role in functional recovery after ischemic stroke. Paeoniflorin, the principal active component of Paeoniae Radix, has been verified to exhibit neuroprotective roles in cerebralischemic injury. However, the mechanisms underlying the regulatory function of Paeoniflorin on neurovascular unit after cerebral ischemia are still unclear.
View Article and Find Full Text PDFOrexin is a neuropeptide that is primarily synthesized and secreted by the lateral hypothalamus (LH) and includes two substances derived from the same precursor (orexin A [OXA] and orexin B [OXB]). Studies have shown that orexin is not only involved in the regulation of eating, the sleep-wake cycle, and energy metabolism, but also closely associated with various physiological functions, such as cardiovascular control, reproduction, stress, reward, addiction, and the modulation of pain transmission. At present, studies that have been performed both domestically and abroad have confirmed that orexin and its receptors are closely associated with pain regulation.
View Article and Find Full Text PDFGlioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery, chemotherapy, radiotherapy, and other comprehensive treatments are the main treatment modalities, but patients still have a poor prognosis mainly due to the infiltrative growth of GBM and the protective effect of the blood-brain barrier on tumor cells. Therefore, immunotherapy is expected to be a good option for GBM.
View Article and Find Full Text PDFNeuroblastoma (NB) is a paediatric tumour that shows great biomolecule and clinical heterogeneity, and patients with NB often develop various neurological complications. Currently, the disease is mainly treated by surgery and still lacks specific therapeutic drugs; therefore, targets are urgently needed. Makorin ring finger protein 2 (MKRN2) is an E3 ligase whose effects on neuroblastoma have not been illustrated.
View Article and Find Full Text PDFJ Cardiothorac Vasc Anesth
September 2020
Objective: The present study investigated the incidence of and risk factors for emergence agitation (EA) in adult patients after thoracoscopic lung surgery.
Design: A retrospective case-control study.
Setting: Single-center university hospital.
Emission trading system is a significant market-based environmental regulation tool worldwide. This study fills existing knowledge gap on whether ETSs have "weak" and "strong" version of Porter hypothesis effects in China, by examining the effects of the Chinese SO emission trading on corporate innovation and productivity. Using the micro-data of domestic-listed manufacturing companies from 2004 to 2015, this study regarded China's SO emission trading system as a quasi-natural experiment by applying a difference-in-difference framework to eliminate endogenous problems.
View Article and Find Full Text PDFExosomes, as a type of extracellular vesicle (EV), are lipid bilayer vesicles 20-100 nm in diameter that can cross the blood-brain barrier. Exosomes are important transport vesicles in the human body that participate in many conduction pathways and play an important physiological role. Because of their high biocompatibility and low immunogenicity and toxicity, exosomes have attracted increasing attention as an attractive drug delivery system.
View Article and Find Full Text PDFC-Jun N-terminal kinase (JNK) is a pivotal MAPK (mitogen-activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK-IN-8 in ischemic stroke and the mechanisms underlying of JNK-IN-8 about neuroprotection are not well understood.
View Article and Find Full Text PDFGlioblastoma (GBM) ranks the most common and aggressive primary brain malignant tumor worldwide. However, the survival rates of patients remain very poor. Therefore, molecular oncology of GBM are urgently needed.
View Article and Find Full Text PDFPurpose: Episodes of acute emotional or physical stress can have significant adverse effects on the hippocampus. Ginsenoside Rb1, the most predominant ginsenoside present in Panax species, has been reported to show a neuroprotective effect. The purpose of this study was to investigate the influence of ginsenoside Rb1 on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) levels in rats subjected to acute immobilization stress.
View Article and Find Full Text PDFObjective: This study was designed to assess clinical predictors of hypoxemia and develop an artificial neural network (ANN) model for prediction of hypoxemia during sedation for gastrointestinal endoscopy examination.
Methods: A total of 220 patients were enrolled in this prospective observational study. Data on demographics, chronic concomitant disease information, neck circumference, thyromental distance and anaesthetic dose were collected and statistically analysed.
Although adipose derived stem cells (ADSCs) exert their therapeutic potential in ischemic stroke, the migration of ADSCs in injured area is not apparently observed after intravenous administration. ADSCs are an important source of exosomes which hold great promise as an endogenous drug delivery system for the treatment of cerebral ischemia given their ability to cross the blood-brain barrier. Here we investigated whether ADSCs-derived exosomes mediated miRNAs transfer and thus promoted neurological recovery after stroke.
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