• Humans
• Anemia, Aplastic/drug therapy
• Middle Aged
• Male
• Female
• Adult
• Retrospective Studies
• Immunosuppressive Agents/therapeutic use
• Immunosuppressive Agents/adverse effects
• Aged
• Pyrazoles/adverse effects
• Pyrazoles/therapeutic use
• Adolescent
• Child
• Young Adult
• Drug Therapy, Combination
• Receptors, Thrombopoietin/agonists
• Treatment Outcome
• Hydrazines/therapeutic use
• Hydrazines/adverse effects
• Hydrazines/administration & dosage
• Hydrazones/therapeutic use
• Hydrazones/adverse effects
• Thiazoles
• Thiophenes

• ADMET
• Eltrombopag olamine
• Forced Degradation
• Molecular Docking
• Related Substances

• Pyrazoles/chemistry
• Pyrazoles/analysis
• Pyrazoles/pharmacology
• Drug Contamination
• Hydrazines/chemistry
• Benzoates/chemistry
• Drug Discovery/methods
• Chromatography, High Pressure Liquid/methods
• Computer Simulation
• Molecular Docking Simulation
• Humans
• Spectrometry, Mass, Electrospray Ionization/methods

• Enterococci
• antimicrobial
• drug repurposing
• lusutrombopag
• resistance

• United States
• Aminoglycosides/pharmacology
• Vancomycin/pharmacology
• Pharmaceutical Preparations
• Drug Repositioning
• Microbial Sensitivity Tests
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use
• Vancomycin-Resistant Enterococci
• Cinnamates
• Thiazoles

• AutoBioSeqpy
• Deep learning
• Thrombocytopenia
• Wedelolactone

• Animals
• Mice
• Artificial Intelligence
• Thrombopoiesis
• Neural Networks, Computer
• Algorithms
• Thrombocytopenia/drug therapy

Thrombocytopenia is one of the most common complications of cancer therapy. Until now, there are still no satisfactory medications to treat chemotherapy and radiation-induced thrombocytopenia (CIT and RIT, respectively). Caulis Polygoni Multiflori (CPM), one of the most commonly used Chinese herbs, has been well documented to nourish blood for tranquilizing the mind and treating anemia, suggesting its beneficial effect on hematopoiesis. However, it is unknown whether CPM can accelerate megakaryopoiesis and thrombopoiesis. Here, we employ a UHPLC Q–Exactive HF-X mass spectrometer (UHPLC QE HF-X MS) to identify 11 ingredients in CPM. Then, in vitro experiments showed that CPM significantly increased megakaryocyte (MK) differentiation and maturation but did not affect apoptosis and lactate dehydrogenase (LDH) release of K562 and Meg-01 cells. More importantly, animal experiments verified that CPM treatment markedly accelerated platelet recovery, megakaryopoiesis and thrombopoiesis in RIT mice without hepatic and renal toxicities in vivo. Finally, RNA-sequencing (RNA-seq) and western blot were used to determine that CPM increased the expression of proteins related to PI3K/Akt and MEK/ERK (MAPK) signaling pathways. On the contrary, blocking PI3K/Akt and MEK/ERK signaling pathways with their specific inhibitors suppressed MK differentiation induced by CPM. In conclusion, for the first time, our study demonstrates that CPM may be a promised thrombopoietic agent and provide an experimental basis for expanding clinical use.

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. In addition, clinical thrombolytics suffer from a short half-life, inactivation, allergic reactions, and non-specific tissue targeting. Another problem is the limited ability of current neuroprotective agents to promote recovery of the ischemic brain tissue after stroke, which contributes to the progressive and irreversible nature of ischemic stroke and also the severity of the outcome. Fortunately, because of biomaterials’ inherent biochemical and biophysical properties, including biocompatibility, biodegradability, renewability, nontoxicity, long blood circulation time, and targeting ability. Utilization of them has been pursued as an innovative and promising strategy to tackle these challenges. In this review, special emphasis will be placed on the recent advances in the study of nanomaterials for the diagnosis and therapy of ischemic stroke. Meanwhile, nanomaterials provide much promise for neural tissue salvage and regeneration in brain ischemia, which is also highlighted.

• National Natural Science Foundation of China

• apoptosis
• ischemia/reperfusion
• mitochondria
• regulated cell death
• small molecule

• Fostamatinib
• ITP, Immune
• Spleen tyrosine kinase inhibitor
• thrombocytopenia

• ICU
• acute respiratory failure
• mortality
• platelet count

• Avatrombopag
• Clinical development
• Thrombocytopenia
• Thrombopoietin receptor agonist

This manuscript demonstrates how integrated bioinformatic and statistical reanalysis of publicly available genomic datasets can be utilized to identify molecular pathways and biomarkers that may be clinically relevant to metastatic prostate cancer (mPrCa) progression. The most notable observation is that the transition from primary prostate cancer to mPrCa is characterized by upregulation of processes associated with DNA replication, metastasis, and events regulated by the serine/threonine kinase PLK1. Moreover, our analysis also identified over-expressed genes that may be exploited for potential targeted therapeutics and minimally invasive diagnostics and monitoring of mPrCa. The primary data analyzed were two transcriptional datasets for tissues derived from normal prostate, primary prostate cancer, and mPrCa. Also incorporated in the analysis were the transcriptional, gene dependency, and drug response data for hundreds of cell lines, including those derived from prostate cancer tissues.

Our understanding of metastatic prostate cancer (mPrCa) has dramatically advanced during the genomics era. Nonetheless, many aspects of the disease may still be uncovered through reanalysis of public datasets. We integrated the expression datasets for 209 PrCa tissues (metastasis, primary, normal) with expression, gene dependency (GD) (from CRISPR/cas9 screen), and drug viability data for hundreds of cancer lines (including PrCa). Comparative statistical and pathways analyses and functional annotations (available inhibitors, protein localization) revealed relevant pathways and potential (and previously reported) protein markers for minimally invasive mPrCa diagnostics. The transition from localized to mPrCa involved the upregulation of DNA replication, mitosis, and PLK1-mediated events. Genes highly upregulated in mPrCa and with very high average GD (~1) are potential therapeutic targets. We showed that fostamatinib (which can target PLK1 and other over-expressed serine/threonine kinases such as AURKA, MELK, NEK2, and TTK) is more active against cancer lines with more pronounced signatures of invasion (e.g., extracellular matrix organization/degradation). Furthermore, we identified surface-bound (e.g., ADAM15, CD276, ABCC5, CD36, NRP1, SCARB1) and likely secreted proteins (e.g., APLN, ANGPT2, CTHRC1, ADAM12) that are potential mPrCa diagnostic markers. Overall, we demonstrated that comprehensive analyses of public genomics data could reveal potentially clinically relevant information regarding mPrCa.

• PLK1
• expression
• genetic dependency
• metastasis
• prostate cancer

• blood-clotting
• growth factor mimetics
• peptide
• sealant
• wound healing

• acute radiation syndrome
• delayed effects of acute radiation exposure
• radiation countermeasures
• regulatory agencies
• repurposing

• AE, adverse event
• CLD, chronic liver disease
• CT, computerised tomography
• GCP, Good Clinical Practice
• HR, hazard ratio
• ICF, informed consent form
• ICH, International Conference on Harmonisation
• ITT, intention-to-treat
• LUSU, lusutrombopag
• Lusutrombopag
• MRI, magnetic resonance imaging
• Magnitude
• PBO, placebo
• PP, per protocol
• PT, platelet transfusion
• Platelet
• Procedural
• TCP, thrombocytopaenia
• TEAE, treatment-emergent adverse event
• Thrombocytopaenia
• US, ultrasonography
• WHO, World Health Organization

• eltrombopag
• pregnancy
• systemic lupus erythematosus
• thrombocytopenia

• AKR-501
• Avatrombopag maleate
• TPO-RA
• chemotherapy-induced thrombocytopenia
• chronic liver disease
• immune thrombocytopenia
• thrombocytopenia
• thrombopoietin
• thrombopoietin receptor agonist

Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease (CLD), leading to challenging perioperative planning. As thrombocytopenia in CLD is associated with thrombopoietin (TPO) deficiency, the use of TPO-receptor agonists (TPO-RAs) to increase platelet counts is a promising approach. This has led to the development of various TPO-RAs, including romiplostim, eltrombopag, avatrombopag, and lusutrombopag. Of these, only avatrombopag and lusutrombopag are approved by the United States Food and Drug Administration for the perioperative treatment of thrombocytopenia in patients with CLD. Platelet transfusion is commonly used for the clinical management of thrombocytopenia in patients with CLD undergoing invasive procedures. However, the limitations and possible risks of transfusion, including short duration of efficacy, development of antiplatelet antibodies, risk of infections and such complications as transfusion-related acute lung injury or circulatory overload, and possibility of refractoriness, limit its use. Moreover, there is no consensus among guidelines as to the platelet count at which transfusions are indicated. Results from studies using TPO-RAs perioperatively in patients with thrombocytopenia and CLD are promising and provide an alternative to platelet transfusions in the pre- and post-operative setting. These TPO-RAs are the subject of this review, with focus on their use in the perioperative setting in patients with thrombocytopenia, associated supporting clinical trials, efficacy and safety data, and their use with respect to platelet transfusions.

• Chronic liver disease
• Thrombocytopenia
• Thrombopoietin
• Receptor agonist
• Avatrombopag
• Lusutrombopag
• Romiplostim
• Perioperative