Enhanced Apc adenoma formation after epithelial CUL4B deletion by recruitment of myeloid-derived suppressor cells.

Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the APC gene, leading to the formation of benign polyps. Despite the well-established role of APC, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood.

VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.

Background: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se.

Inhibition of GABAA receptors in intestinal stem cells prevents chemoradiotherapy-induced intestinal toxicity.

Lethal intestinal tissue toxicity is a common side effect and a dose-limiting factor in chemoradiotherapy. Chemoradiotherapy can trigger DNA damage and induce P53-dependent apoptosis in LGR5+ intestinal stem cells (ISCs). Gamma-aminobutyric acid (GABA) and its A receptors (GABAAR) are present in the gastrointestinal tract.

Platelets fine-tune effector responses of naïve CD4 T cells via platelet factor 4-regulated transforming growth factor β signaling.

Background And Aim: Platelets are an able regulator of CD4 T cell immunity. Herein, the mechanisms underlying platelet-regulated effector responses of naïve CD4 T (Tn) cells were investigated.

Methods: Platelet-Tn cell co-cultures of human cells, genetically modified murine models, and high-throughput bioinformatic analyses were combined to elucidate molecular mechanisms of platelet-dependent regulation.

Establishment and Genetic Manipulation of Murine Hepatocyte Organoids.

The liver is the largest organ in mammals. It plays an important role in glucose storage, protein secretion, metabolism and detoxification. As the executor for most of the liver functions, primary hepatocytes have limited proliferating capacity.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

Background And Aims: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway.

Platelets enhance CD4+ central memory T cell responses via platelet factor 4-dependent mitochondrial biogenesis and cell proliferation.

Platelets regulate multiple aspects of CD4 T cell immunity, and may exert distinct regulations among different T cell subsets. Our aim was to investigate how platelets regulate CD4 central memory T cell (Tcm) responses. αCD3/αCD28-stimulated human CD4 Tcm cells were cultured without or with platelets or platelet-derived mediators.

VEGFR2 inhibition hampers breast cancer cell proliferation enhanced mitochondrial biogenesis.

Objective: Vascular endothelial growth factor (VEGF), apart from its predominant roles in angiogenesis, can enhance cancer cell proliferation, but its mechanisms remain elusive. The purpose of the present study was therefore to identify how VEGF regulates cancer cell proliferation.

Methods: VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor, Ki8751, and the breast cancer cell lines, MCF-7 and MDA-MB-231, using flow cytometry, mass spectrometry, immunoblotting, and confocal microscopy.

Platelet factor 4 enhances CD4 T effector memory cell responses via Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis.

Background: Cell metabolism drives T cell functions, while platelets regulate overall CD4 T cell immune responses.

Objective: To investigate if platelets influence cell metabolism and thus regulate CD4 T effector memory cell (Tem) responses.

Methods: Human CD4 Tem cells were activated with αCD3/αCD28 and cultured without or with platelets or platelet-derived mediators.

Intradermal Injection of Oxytocin Aggravates Chloroquine-Induced Itch Responses Activating the Vasopressin-1a Receptor/Nitric Oxide Pathway in Mice.

Oxytocin (OT), a hormone synthesized within the paraventricular nucleus and supraoptic nucleus of the hypothalamus, when given intracerebroventricularly, induces strong scratching behaviors. However, it is not clear whether intradermal injection (ID) of OT elicits itch sensation. Herein, we found that OT (0.

Flavonoids in a crude extract of Catha edulis inhibit rat intestinal contraction via blocking Ca channels.

Background: Animal studies show that Catha edulis inhibits gastrointestinal tract motility. However, there is little or no information on its effect on colon motility and the mechanism of action and active constituents responsible for this effect. This study therefore attempted to discern the effect, suggest the mechanism, and identify the active compounds from the crude extract.

Oxytocin involves in chronic stress-evoked melanoma metastasis via β-arrestin 2-mediated ERK signaling pathway.

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation.

Morphologic Evolution and Coordinated Development of the Fetal Lateral Ventricles in the Second and Third Trimesters.

Background And Purpose: Few investigators have studied the lateral ventricle formation related to the development of the calcarine sulcus. Our purpose was to establish the relationship between the lateral ventricles and the calcarine sulcus in the second and third trimesters.

Materials And Methods: Fetal brain MR imaging (3T and 7T) was performed in 84 fetuses at 14-35 gestational weeks.

Hydrogen sulfide downregulates colonic afferent sensitivity by a nitric oxide synthase-dependent mechanism in mice.

Background: The effect of hydrogen sulfide (H S) on visceral nociception is elusive. The conflicting evidence of its pro- and antinociceptive effects raises a series of questions with respect to the effect of H S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study.

Methods: Colonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs mice, and Wistar rats were recorded in vitro.

Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve.

This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy.