Amelioration of metabolic and behavioral defects through base editing in the Pah phenylketonuria mouse model.

Phenylketonuria (PKU) is a liver metabolic disorder mainly caused by a deficiency of the hepatic phenylalanine hydroxylase (PAH) enzyme activity, often leading to severe brain function impairment in patients if untreated or if treatment is delayed. In this study, we utilized dual-AAV8 vectors to deliver a near PAM-less adenine base editor variant, known as ABE8e-SpRY, to treat the Pah PKU mouse model carrying a frequent R408W mutation in the Pah gene. Our findings revealed that a single intravenous injection in adult mice and a single intraperitoneal injection in neonatal mice resulted in 19.

Aspirin increases estrogen levels in the placenta to prevent preeclampsia by regulating placental metabolism and transport function.

Preeclampsia is a unique multisystem progressive disease during pregnancy, which seriously endangers the health of pregnant women and fetuses. In clinical practice, aspirin is recommended for the prevention of preeclampsia, but the mechanism by which aspirin prevents preeclampsia has not yet been revealed. This report comprehensively evaluates the effects of aspirin on the expression and activity of placental metabolic enzymes and transporters.

BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise.

Background: Resistance exercise leads to improved muscle function and metabolic homeostasis. Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.

Methods: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin.

Role of epoxyeicosatrienoic acids in cardiovascular diseases and cardiotoxicity of drugs.

Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs.

Aging-associated REGγ proteasome decline predisposes to tauopathy.

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei.

Emerging role of carboxylesterases in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health problem. Carboxylesterases (CESs), as potential influencing factors of NAFLD, are very important to improve clinical outcomes. This review aims to deeply understand the role of CESs in the progression of NAFLD and proposes that CESs can be used as potential targets for NAFLD treatment.

Hypercholesterolemia reduces the expression and function of hepatic drug metabolizing enzymes and transporters in rats.

Hypercholesterolemia, one of the most common lipid metabolic diseases, may cause severe complications and even death. However, the effect of hypercholesterolemia on drug-metabolizing enzymes and transporters remains unclear. In this report, we established a rat model of diet-induced hypercholesterolemia.

Intranasal administration of white tea alleviates the olfactory function deficit induced by chronic unpredictable mild stress.

Context: White tea [ (L) O.Ktze. (Theaceae)] is popular in Asia, but its benefits on olfactory injury are unknown.

Proteasome activator PA28γ-dependent degradation of coronavirus disease (COVID-19) nucleocapsid protein.

The nucleocapsid protein is significant in the formation of viral RNA of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accounting for the largest proportion of viral structural proteins. Here, we report for the first time that the 11S proteasomal activator PA28γ regulates the intracellular abundance of the SARS-CoV-2 N protein (nCoV N). Furthermore, we have identified proteasome activator PA28γ as a nCoV N binding protein by co-immunoprecipitation assay.

Age-specific effects of P2X7 receptors on olfactory function in mice.

This study aimed to explore the age-specific effects of P2X7 receptor (P2X7R) knockout on olfactory function in mice. In this study, we analyzed olfactory functions of 2-month-old, 10-month-old and 18-month-old female P2X7R KO mice and age-matched female C57BL/6 wildtype mice (WT mice) by buried food seeking test and olfactory avoidance test. The structure of mitochondria and synapses in olfactory bulb were observed by electron microscopy.

The effects of P2X7 receptor knockout on emotional conditions over the lifespan of mice.

Neuroinflammation is one of the key factors contributing to depression. Recent studies have identified P2X7 receptor (P2X7r) as a major inflammatory regulator. However, the effects of P2X7r knockout (KO) on emotional conditions over the lifespan of mice are unknown.

Antidiabetic and Neuroprotective Effect of the N-Butanol Extract of Schlecht. in STZ-Induced Diabetic Mice.

Diabetes has been associated with neurodegenerative disorders that are accompanied by memory loss and cognitive impairments, but there is no effective treatment for it at present. Schlecht. (FNS), a well-known Chinese materia medica, has been traditionally used for the folkloric treatment of diabetes and other diseases.

Hypolipidemic effect of Fragarianilgerrensis Schlecht. medicine compound on hyperlipidemic rats.

Background: Fragarianilgerrensis Schlecht. medicine compound (FN-MC) is a kind of Chinese herbs' compound consisted of Fragarianilgerrensis Schlecht. and Centella asiatica (L.

Effect of Motion Perception on Intertemporal Choice Is Associated With the Altered Time Perception.

Intertemporal choice refers to the choice between receiving a small immediate reward or a large delayed one. Previous studies have indicated that time perception plays a critical role in the intertemporal choice, and it could be affected by the features of the target stimulus in the time reproduction task, such as speed of movement and state of motion. However, there is no evidence about whether backward or forward motion perception could alter the intertemporal choice.

Folic acid exerts antidepressant effects by upregulating brain-derived neurotrophic factor and glutamate receptor 1 expression in brain.

Folic acid is a vitamin with a variety of pharmacological effects. The present study aims to explore the beneficial effects of folic acid on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including open-field test, tail suspension test, and forced swimming test were used to evaluate the antidepressant effects of folic acid.

Presenilin 2 deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression.

Accumulating evidence suggests that β-amyloid (Aβ)-induced neuroinflammation plays a prominent and early role in Alzheimer's disease (AD). In this study, we demonstrated that Presenilin 2 (PS2) deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression both in vitro and in vivo. PS2 knockout mice demonstrated increased cognitive impairments and cerebral injury.