Cytohesin-4/ARF6 facilitates the progression of acute myeloid leukemia through activating PIK3R5/PI3K/AKT pathway.

analysis revealed an elevated expression of cytohesin-4 (CYTH4) in acute myeloid leukemia (AML) cells, correlating with a poorer prognosis for AML patients. However, its role in AML is not fully understood. Our study using loss-of-function assays identified CYTH4 as an oncogene promoting leukemogenesis.

function reveals temporal differences in neural subtype generation in cnidarians.

Understanding how cnidarians pattern their nervous systems can provide insight into the ancestral mechanisms of neurogenesis that are shared with bilaterians, shedding light on the evolution of nervous systems. While previous studies have revealed deeply conserved mechanisms for neural induction and progenitor selection between cnidarians and bilaterians, less is known about how distinct neuronal subtypes are specified over time in cnidarians. We utilized single-cell mRNA sequencing to profile expressing cells across embryonic and planula-larva stages of neurogenesis, and functional experiments identified a dynamic role for over time.

Allisartan isoproxil reduces mortality of stroke-prone rats and protects against cerebrovascular, cardiac, and aortic damage.

Stroke is a common cause of death and disability. Allisartan isoproxil (ALL) is a new angiotensin II receptor blocker and a new antihypertensive drug discovered and developed in China. In the present study we investigated the therapeutic effects of ALL in stroke-prone renovascular hypertensive rats (RHR-SP) and the underlying mechanisms.

Cerebral organoids transplantation improves neurological motor function in rat brain injury.

Background And Purpose: Cerebral organoids (COs) have been used for studying brain development, neural disorders, and species-specific drug pharmacology and toxicology, but the potential of COs transplantation therapy for brain injury remains to be answered.

Methods: With preparation of traumatic brain injury (TBI) model of motor dysfunction, COs at 55 and 85 days (55 and 85 d-CO) were transplanted into damaged motor cortex separately to identify better transplantation donor for brain injury. Further, the feasibility, effectiveness, and underlying mechanism of COs transplantation therapy for brain injury were explored.

Aggravated ulcerative colitis caused by intestinal Metrnl deficiency is associated with reduced autophagy in epithelial cells.

Metrnl is a newly identified secreted protein highly expressed in the intestinal epithelium. This study aimed to explore the role and mechanism of intestinal epithelial Metrnl in ulcerative colitis. Metrnl (intestinal epithelial cell-specific Metrnl knockout) mice did not display any phenotypes of colitis under basal conditions.

Cerebral Organoids Repair Ischemic Stroke Brain Injury.

Stroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered.

Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats.

Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes.

NAD replenishment with nicotinamide mononucleotide protects blood-brain barrier integrity and attenuates delayed tissue plasminogen activator-induced haemorrhagic transformation after cerebral ischaemia.

Background And Purpose: Tissue plasminogen activator (tPA) is the only approved pharmacological therapy for acute brain ischaemia; however, a major limitation of tPA is the haemorrhagic transformation that follows tPA treatment. Here, we determined whether nicotinamide mononucleotide (NMN), a key intermediate of nicotinamide adenine dinucleotide biosynthesis, affects tPA-induced haemorrhagic transformation.

Experimental Approach: Middle cerebral artery occlusion (MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.

Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor.

Alpha7 nicotinic acetylcholine receptor (α7nAChR) has been reported to alleviate neuroinflammation. Here, we aimed to determine the role of autophagy in α7nAChR-mediated inhibition of neuroinflammation and its underlying mechanism. Experimental autoimmune encephalomyelitis (EAE) mice and lipopolysaccharide-stimulated BV2 microglia were used as and models of neuroinflammation, respectively.

Diurnal Variation of the Peripheral Cholinergic Antiinflammatory Function in Mice.

Aims: Cholinergic antiinflammatory (CAI) pathway functions importantly in inflammation via α7 nicotinic acetylcholine receptors (α7nAChR). The present work tested circadian rhythm in peripheral CAI activity and validities of CAI activity and glucocorticoids in chronotherapy for lipopolysaccharide (LPS)-induced shock.

Methods: Vesicular acetylcholine transporter (VAChT) expressed in liver and kidney was examined every 3 h in C57BL/6 mice.

Sodium Sulfide, a Hydrogen Sulfide-Releasing Molecule, Attenuates Acute Cerebral Ischemia in Rats.

Aims: Acute cerebral ischemia may lead to ischemic stroke, which is a major cause of death and disability worldwide. Hydrogen sulfide (H2 S) functions importantly in mammalian systems. The present work was designed to study the effect of sodium sulfide, a donor of H2 S, on acute cerebral ischemia.

MicroRNA-124 negatively regulates LPS-induced TNF-α production in mouse macrophages by decreasing protein stability.

Aim: MicroRNAs play pivotal roles in regulation of both innate and adaptive immune responses. In the present study, we investigated the effects of microRNA-124 (miR-124) on production of the pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-treated mouse macrophages.

Methods: Mouse macrophage cell line RAW264.

Monoterpenoid indole alkaloids from Alstonia rupestris with cytotoxic, anti-inflammatory and antifungal activities.

Phytochemical investigation of the 70% EtOH extract of the leaves of Alstonia scholaris afforded seven new monoterpenoid indole alkaloids: scholarisins I-VII (1-7), and three known compounds: (3R,5S,7R,15R,16R,19E)-scholarisine F (8), 3-epi-dihydro- corymine (9), and (E)-16-formyl-5α-methoxystrictamine (10). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxicity against seven tumor cell lines, anti-inflammatory activities against Cox-1 and Cox-2, and antifungal potential against five species of fungi.

Inhibition of extracellular signal-regulated kinase activity by sorafenib increases sensitivity to DNR in K562 cells.

The mitogen-activated protein kinase (MAPK) pathway has a protective function on the management of hematologic malignancies. The aim of this study was to assess whether the induction of MAPK-mediated effects contributes to the therapeutic value of combination sorafenib and daunorubicin (DNR) treatment. Herein, we found that DNR increased phosphorylation of extracellular signal-regulated kinases (ERK1/2) in K562 cells.

[Sorafenib induces apoptosis of U937 cells via inhibiting WNT signal pathway].

This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot.

[Effect of sorafenib combined with daunorubicin on K562 cell line].

The aim of this study was to investigate the effect of sorafenib combined with daunorubicin on leukemic k562 cell line. The inhibitory effect of sorafenib alone and its combination with daunorubicin on K562 cell proliferation was detected by MTT method; the synergistic effect was measured by CDI (coefficient of drug interaction); the apoptosis of K562 cells was observed by flow cytometry with Hoechst 33258 staining. The results showed that the sorafenib alone or its combination with daunorubicin could significantly inhibit K562 cell proliferation and the combination of both drugs displayed synergistic effect on K562 cells, meanwhile the apoptotic cells increased.

Effects of Changtai granules, a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats.

Aim: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats.

Methods: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol.

Inhibitors of 5-lipoxygenase inhibit expression of intercellular adhesion molecule-1 in human melanoma cells.

Aim: To study the effect of 5-lipoxygenase inhibitors on the expression of intercellular adhesion molecule-1 (ICAM-1) in melanoma cells.

Methods: ICAM-1 protein of human melanoma cell a375 was detected by enzyme-linked immunosorbent, flow cytometry and Western blot analysis. Level of ICAM-1 mRNA in a375 was evaluated by Northern blot analysis.