PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling.

Recently, changes in metabolites and metabolism-related enzymes related to tumor cell proliferation, metastasis, drug resistance, and immunosuppression have become a research hotspot, and researchers have attempted to determine the clinical correlation between specific molecular lesions and metabolic phenotypes. Convincing evidence shows that metabolic reprogramming is closely related to the proliferation, invasion, metastasis, and poor prognosis of malignant tumors. Therefore, targeting metabolic reprogramming is a new direction for cancer treatment.

Nicotinamide adenine dinucleotide phosphate alleviates intestinal ischemia/reperfusion injury via Nrf2/HO-1 pathway.

Intestinal ischemia-reperfusion (I/R) injury is a critical condition in the abdomen that has significant morbidity and fatality rates. Prior studies have noted the defensive role of the coenzymatic antioxidant reduced nicotinamide adenine dinucleotide phosphate (NADPH) in heart and brain I/R damage, yet its impact on intestinal I/R trauma required further exploration. Through the application of an in vitro oxygen-glucose deprivation-reoxygenation model and a mouse model of short-term intestinal I/R, this study clarified the defensive mechanisms of NADPH against intestinal I/R injury.

O-GlcNAcylation in ischemic diseases.

Protein glycosylation is an extensively studied field, with the most studied forms being oxygen or nitrogen-linked N-acetylglucosamine (O-GlcNAc or N-GlcNAc) glycosylation. Particular residues on proteins are targeted by O-GlcNAcylation, which is among the most intricate post-translational modifications. Significantly contributing to an organism's proteome, it influences numerous factors affecting protein stability, function, and subcellular localization.

Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review.

Alzheimer's disease is characterized by two major neuropathological hallmarks-the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer's disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics.

Hyperglycemia Aggravates the Cerebral Ischemia Injury via Protein O-GlcNAcylation.

Background: At least one-third of Alzheimer's disease (AD) patients have cerebrovascular abnormalities, micro- and macro-infarctions, and ischemic white matter alterations. Stroke prognosis impacts AD development due to vascular disease. Hyperglycemia can readily produce vascular lesions and atherosclerosis, increasing the risk of cerebral ischemia.

Mori fructus aqueous extracts attenuate carbon tetrachloride-induced renal injury via the Nrf2 pathway and intestinal flora.

Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl).

AKT/GSK-3β signaling is altered through downregulation of mTOR during cerebral Ischemia/Reperfusion injury.

Purpose: Cellular responses following cerebral ischemia/reperfusion injury are critical to recovery and survival after ischemic stroke. Understanding of these cellular responses can help the design of therapies to protect brain tissue and promote recovery after stroke. One of these cellular responses may be mediated by the AKT (protein kinase B) signal transduction pathway.

Timely and Appropriate Administration of Inhaled Argon Provides Better Outcomes for tMCAO Mice: A Controlled, Randomized, and Double-Blind Animal Study.

Background: Inhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke and has exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration, and time point of iAr for acute ischemic stroke are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion injury.

Excess folic acid supplementation before and during pregnancy and lactation activates β-catenin in the brain of male mouse offspring.

Folic acid (FA) supplementation in early pregnancy is recommended to protect against birth defects. But excess FA has exhibited neurodevelopmental toxicity. We previously reported that the mice treated with 2.

Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.

Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion.

Neuroprotective effects of oleanolic acid against cerebral ischemia-reperfusion injury in mice.

Background/aim: Stroke is among the most common causes of disability and death in highly developed countries and China. We sought to study the role of oleanolic acid in cerebral ischemia-reperfusion injury.

Methods: Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia-reperfusion injury in mice.

Selenomethionine protects hematopoietic stem/progenitor cells against cobalt nanoparticles by stimulating antioxidant actions and DNA repair functions.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) can differentiate into all blood lineages to maintain hematopoiesis, wound healing, and immune functions. Recently, cobalt-chromium alloy casting implants have been used extensively in total hip replacements; however, cobalt nanoparticles (CoNPs) released from the alloy were toxic to HSCs and HPCs. We aimed to investigate the mechanism underlying the toxic effect of CoNPs on HSCs/HPCs and to determine the protective effect of selenomethionine (SeMet) against CoNPs and .

Thiamme2-G, a Novel O-GlcNAcase Inhibitor, Reduces Tau Hyperphosphorylation and Rescues Cognitive Impairment in Mice.

Background: Abnormal hyperphosphorylation of microtubule-associated protein tau plays a pivotal role in Alzheimer's disease (AD). We previously found that O-GlcNAcylation inversely correlates to hyperphosphorylation of tau in AD brain, and downregulation of brain O-GlcNAcylation promotes tau hyperphosphorylation and AD-like neurodegeneration in mice.

Objective: Herein we investigated the effect of increasing O-GlcNAcylation by using intermittent dosing with low doses of a potent novel O-GlcNAcase (OGA) inhibitor on AD-like brain changes and cognitive function in a mouse model of sporadic AD (sAD) induced by intracerebroventricular (ICV) injection of streptozotocin (STZ).

Protein O-GlcNAcylation alleviates small intestinal injury induced by ischemia-reperfusion and oxygen-glucose deprivation.

Protein O-GlcNAcylation is a dynamic post-translational protein modification that regulates fundamental cellular functions in both normal physiology and diseases. The levels of protein O-GlcNAcylation are determined by flux of the hexosamine biosynthetic pathway (HBP), which is a branch of glycolysis, and are directly controlled by a pair of enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). An increase in protein O-GlcNAcylation has been shown to have protective effects on ischemia-related insults in the heart and brain.

A paradox: Fe2+-containing agents decreased ROS and apoptosis induced by CoNPs in vascular endothelial cells by inhibiting HIF-1α.

Cobalt nanoparticles (CoNPs) released from hip joint implants are known to have a toxic effect on several organs probably through increasing reactive oxygen species (ROS). Ferrous ion (Fe2+) is well-known to enhance oxidative stress by catalysing the production of ROS. However, in our pilot study, we found that Fe2+ conversely inhibited the ROS production induced by CoNPs.

Serum level of interleukin-35 as a potential prognostic factor for gastric cancer.

Aims: Interleukin-35 (IL-35), a novel anti-inflammatory cytokine, has recently been implicated in tumor development, progression, and survival. However, the relationship between serum IL-35 levels and gastric cancer (GC) is inconclusive. Here, we performed this study to clarify the role of serum level of IL-35 in GC patients.

Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death.

As a main element in the hard metal industry, cobalt is one of the major components of human metal implants. Cobalt-containing implants, especially joint prostheses used for artificial joint replacement, can be corroded due to the complex physiological environment in vivo, producing a large number of nanoscale cobalt particles (Cobalt Nanoparticles, CoNPs). These CoNPs can be first accumulated around the implant to cause adverse local reactions and then enter into the blood vessels followed by reaching the liver, heart, brain, kidney, and other organs through systematic circulation, which leads to multi-system toxicity symptoms.

Elevated serum levels of interleukin-37 correlate with poor prognosis in gastric cancer.

Background: interleukin-37 (IL-37) is as a natural suppressor of the innate inflammatory and immune responses. It has also been reported to be involved in carcinogenesis and metastasis. The present case-control study was designed to investigate the role of serum levels of IL-37 in patients with gastric cancer.

Intranasal Administration of Insulin Reduces Chronic Behavioral Abnormality and Neuronal Apoptosis Induced by General Anesthesia in Neonatal Mice.

Children, after multiple exposures to general anesthesia, appear to be at an increased risk of developing learning disabilities. Almost all general anesthetics-including sevoflurane, which is commonly used for children-are potentially neurotoxic to the developing brain. Anesthesia exposure during development might also be associated with behavioral deficiencies later in life.

CARE Dose 4D combined with sinogram-affirmed iterative reconstruction improved the image quality and reduced the radiation dose in low dose CT of the small intestine.

Objective: Multislice computed tomography (MSCT) has been used for diagnosis of small intestinal diseases. However, the radiation dose is a big problem. This study was to investigate whether CARE Dose 4D combined with sinogram-affirmed iterative reconstruction (SAFIRE) can provide better image quality at a lower dose for imaging small intestinal diseases compared to MSCT.

Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.

The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism. However, little is known about the function of OGT in the brain.

The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model.

Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia.