Identification of small molecule agonists of fetal hemoglobin expression for the treatment of sickle cell disease.

Induction of fetal hemoglobin (HbF) has been shown to be a viable therapeutic approach to treating sickle cell disease and potentially other β-hemoglobinopathies. To identify targets and target-modulating small molecules that enhance HbF expression, we engineered a human umbilical-derived erythroid progenitor reporter cell line (HUDEP2_HBG1_HiBiT) by genetically tagging a HiBiT peptide to the carboxyl (C)-terminus of the endogenous HBG1 gene locus, which codes for γ-globin protein, a component of HbF. Employing this reporter cell line, we performed a chemogenomic screen of approximately 5000 compounds annotated with known targets or mechanisms that have achieved clinical stage or approval by the US Food and Drug Administration (FDA).

New Monoterpenoid Glycosides from the Fruits of Thunb.

The whole Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises.

Exploring Potential Regulatory Anesthetic Drugs Based on RNA Binding Protein and Constructing CESC Prognosis Model: A Study Based on TCGA Database.

Objective: To investigate the differential expression of RBPs in cervical squamous cell carcinoma (CESC), analyze the regulatory effect of narcotic drugs on RBPs, and establish the prognostic risk model of CESC patients.

Methods: RNA-SEQ data and clinical case data of cancer and normal samples from CESC patients were obtained from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database. Differentially expressed RBPs were screened by R language and enriched.

Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

Background: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery.

Methods: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery.

Multiscale architectures boosting thermoelectric performance of copper sulfide compound.

Unlabelled: Owing to their high performance and earth abundance, copper sulfides (Cu S) have attracted wide attention as a promising medium-temperature thermoelectric material. Nanostructure and grain-boundary engineering are explored to tune the electrical transport and phonon scattering of Cu S based on the liquid-like copper ion. Here multiscale architecture-engineered Cu S are fabricated by a room-temperature wet chemical synthesis combining mechanical mixing and spark plasma sintering.

Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes.

Background: Astrocytes are highly glycolytic cells that play a crucial role in chronic pain. Recently it has been found that inflammation and metabolism are related to the inflammatory stimuli closely that cause cellular metabolic changes. Pyruvate kinase M2 (PKM2) is a critical metabolic kinase in aerobic glycolysis or the Warburg effect.

Effects of nicorandil on p120 expression in the spinal cord and dorsal root ganglion of rats with chronic postsurgical pain.

Chronic postsurgical pain (CPSP) has a high incidence, but the underlying mechanism is not well understood. Accumulating evidence has suggested that central sensitization is the main mechanism of pain. To study the role of p120 in CPSP, a skin/muscle incision and retraction (SMIR) model was established, and immunofluorescence staining and western blotting were performed to analyze the expression of p120 in the spinal cord and dorsal root ganglion (DRG).

A Novel Screening Approach for the Dissection of Cellular Regulatory Networks of NF-κB Using Arrayed CRISPR gRNA Libraries.

CRISPR/Cas9 is increasingly being used as a tool to prosecute functional genomic screens. However, it is not yet possible to apply the approach at scale across a full breadth of cell types and endpoints. In order to address this, we developed a novel and robust workflow for array-based lentiviral CRISPR/Cas9 screening.

Erratum: Low-affinity neurotrophin receptor p75 of brain-derived neurotrophic factor contributes to cancer-induced bone pain by upregulating mTOR signaling.

[This corrects the article DOI: 10.3892/etm.2019.

HDAC6 promotes sepsis development by impairing PHB1-mediated mitochondrial respiratory chain function.

Objective: This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis.

Results: HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury.

Low-affinity neurotrophin receptor p75 of brain-derived neurotrophic factor contributes to cancer-induced bone pain by upregulating mTOR signaling.

Crucial to the development and maintenance of pain sensations is neurotrophin receptor p75 (p75), the low affinity receptor of brain-derived neurotrophic factor (BDNF). This receptor is widespread among dorsal root ganglion (DRG) neurons and the spinal cord. Few reports have demonstrated the specific role of p75 in the development of cancer-induced bone pain (CIBP).

Lipofection-mediated genome editing using DNA-free delivery of the Cas9/gRNA ribonucleoprotein into plant cells.

A novel and robust lipofection-mediated transfection approach for the use of DNA-free Cas9/gRNA RNP for gene editing has demonstrated efficacy in plant cells. Precise genome editing has been revolutionized by CRISPR/Cas9 systems. DNA-based delivery of CRISPR/Cas9 is widely used in various plant species.

Parthenolide ameliorates intracerebral hemorrhage-induced brain injury in rats.

Neuroinflammation and oxidative stress are key contributors to intracranial hemorrhage (ICH)-induced brain injury. Parthenolide (PN) is a sesquiterpene lactone that has been observed to have antioxidative, anti-inflammatory, and neuroprotective potentials. However, the role of PN in ICH remains unclear.

Suppression of WNK1-SPAK/OSR1 Attenuates Bone Cancer Pain by Regulating NKCC1 and KCC2.

Our preliminary experiment indicated the activation of with-nolysine kinases 1 (WNK1) in bone cancer pain (BCP) rats. This study aimed to investigate the underlying mechanisms via which WNK1 contributed to BCP. A rat model of BCP was induced by Walker-256 tumor cell implantation.

microRNA-874 inhibition targeting STAT3 protects the heart from ischemia-reperfusion injury by attenuating cardiomyocyte apoptosis in a mouse model.

MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia-reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR-874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV.

Botulinum toxin-A for the treatment of neuralgia: a systematic review and meta-analysis.

Aim: This meta-analysis was performed to evaluate the efficacy and safety of botulinum toxin-A (BTX-A) for the treatment of neuralgia.

Methods: We searched PubMed, EMBASE, and Cochrane databases to identify randomized controlled trials (RCTs) comparing BTX-A treatment with saline for alleviating neuropathic pain. Primary outcome measures were pain scores up to 24 weeks after treatment.

Astragaloside suppresses tumor necrosis factor receptor-associated factor 5 signaling pathway and alleviates neurodegenerative changes in retinal pigment epithelial cells induced by isoflurane.

Epidemiological studies showed that isoflurane, a general anesthetic widely used in surgery including those for the children, is associated with impairment of neurodevelopment and neurodegenerative diseases, such as Alzheimer's disease (AD) and age-related macular degeneration (AMD), which are related to the accumulation of reactive oxygen species (ROS). Astragaloside (AS) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge. In this study, we used retinal pigment epithelial cells, which share plenty of features with neurodegenerative diseases such as AD and AMD to investigate the effect of AS.

A Comparative Study on Three Treatment Approaches to Applying Topical Botulinum Toxin A for Crow's Feet.

Objective: To evaluate the efficacy and safety of three treatment approaches to applying Botulinum Toxin Type A (BoNTA) for crow's Feet.

Methods: Thirty female subjects with moderate-to-severe crow's feet were included in this comparative study. They were randomly divided into three groups, including the local intramuscular, intradermal microdroplet injection, and nanomicroneedle delivered with BoNTA therapy group.

A systematic review and meta-analysis of two different managements for supracondylar humeral fractures in children.

Background: The objective of this meta-analysis was to illustrate the clinical outcomes and safety of two different managements for supracondylar humeral fractures in children.

Methods: In January 2018, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for two different managements for supracondylar humeral fractures in children were retrieved.

p53 and P-glycoprotein influence chemoresistance in hepatocellular carcinoma.

Chemoresistance is a critical obstacle to the treatment of hepatocellular carcinoma (HCC). The mechanisms underlying resistance to doxorubicin, cisplatin, and 5-fluorouracil involve p53 and P-glycoprotein (P-gp). p53 plays a role in cell growth; therefore, resistance mechanisms involve chemotherapy-induced apoptosis and p53 mutation and inactivation.

Increased diffusion and decreased perfusion in epiphyses of femoral heads detected via intravoxel incoherent motion after closed reduction in children with developmental dysplasia of the hip.

Background Patients with developmental dysplasia of the hip (DDH) may have decreased blood supply to the femoral heads. Finding a non-invasive method to evaluate whether the femoral heads in patients with DDH are ischemic is paramount for orthopedic surgeons. Purpose To identify whether parameters reflecting perfusion and diffusion in intravoxel incoherent motion (IVIM) sequences can be used to assess ischemia in femoral heads in patients with DDH after closed reduction.

Water-soluble Manganese and Iron Mesotetrakis(carboxyl)porphyrin: DNA Binding, Oxidative Cleavage, and Cytotoxic Activities.

Two new water-soluble metal carboxyl porphyrins, manganese (III) -tetrakis (carboxyl) porphyrin and iron (III) -tetrakis (carboxyl) porphyrin, were synthesized and characterized. Their interactions with ct-DNA were investigated by UV-Vis titration, fluorescence spectra, viscosity measurement and CD spectra. The results showed they can strongly bind to ct-DNA via outside binding mode.

Expansion and activation of granulocytic, myeloid-derived suppressor cells in childhood precursor B cell acute lymphoblastic leukemia.

Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies.