G protein-coupled receptors (GPCRs), widely expressed in the human central nervous system (CNS), perform numerous physiological functions and play a significant role in the pathogenesis of diseases. Consequently, identifying key therapeutic GPCRs targets for CNS-related diseases is garnering immense interest in research labs and pharmaceutical companies. However, using GPCRs drugs for treating neurodegenerative diseases has limitations, including side effects and uncertain effective time frame.
View Article and Find Full Text PDFBackground: The KCNQ1+KCNE1 (I) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a fatal neurodegenerative disease in which senile plaques and neurofibrillary tangles are crucially involved in its physiological and pathophysiological processes. Growing animal and clinical studies have suggested that AD is also comorbid with some metabolic diseases, including type 2 diabetes mellitus (T2DM), and therefore, it is often considered brain diabetes. AD and T2DM share multiple molecular and biochemical mechanisms, including impaired insulin signaling, oxidative stress, gut microbiota dysbiosis, and mitochondrial dysfunction.
View Article and Find Full Text PDFIn contrast to its widespread traditional and popular culinary use to reduce weight, (adzuki beans) was not subjected to sufficient scientific scrutiny. Particularly, its saponins whose role was never investigated before to unveil the beans' antidiabetic and anti-obesity effects. Four vital pancreatic and intestinal carbohydrate enzymes were selected to assess the potency of the triterpenoidal saponins of to bind and activate these proteins through high-precision molecular modeling and dynamics mechanisms with accurate molecular mechanics Generalized Born Surface Area (MMGBSA) energy calculations; thus, recognizing their anti-obesity potential.
View Article and Find Full Text PDFWater-soluble inorganic ions (WSIIs, primarily NH, SO, and NO) are major components in ambient PM, but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment.
View Article and Find Full Text PDFVascular etiology is the second most prevalent cause of cognitive impairment globally. Endothelin-1, which is produced and secreted by endothelial cells and astrocytes, is implicated in the pathogenesis of stroke. However, the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.
View Article and Find Full Text PDFEpalrestat, an aldose reductase inhibitor (ARI), has been clinically adopted in treating diabetic neuropathy in China and Japan. Apart from the involvement in diabetic complications, AR has been implicated in inflammation. Here, we seek to investigate the feasibility of clinically approved ARI, epalrestat, for the treatment of rheumatoid arthritis (RA).
View Article and Find Full Text PDFMitochondrial dysfunction has been implicated in Parkinson's Disease (PD) progression; however, the mitochondrial factors underlying the development of PD symptoms remain unclear. One candidate is CR6-interacting factor1 (CRIF1), which controls translation and membrane insertion of 13 mitochondrial proteins involved in oxidative phosphorylation. Here, we found that CRIF1 mRNA and protein expression were significantly reduced in postmortem brains of elderly PD patients compared to normal controls.
View Article and Find Full Text PDFTricin, a natural nontoxic flavonoid distributed in grasses and euphorbia plants, has been reported to scavenge free radicals, possess anti-inflammatory and antioxidative effects. However, its autophagic effect on Parkinson's disease (PD) has not been elucidated. By adopting cellular and C.
View Article and Find Full Text PDFThe microbiota present in the respiratory tract (RT) responds to environmental stimuli and engages in a continuous interaction with the host immune system to maintain homeostasis. A total of 40 C57BL/6 mice were divided into four groups and exposed to varying concentrations of PM nitrate aerosol and clean air. After 10 weeks of exposure, assessments were conducted on the lung and airway microbiome, lung functions, and pulmonary inflammation.
View Article and Find Full Text PDFCardiovascular disease (CVD) remains the leading cause of morbidity and mortality, imposing an increasing global health burden. Cardiac ion channels (voltage-gated Na, Ca, Ks, and others) synergistically shape the cardiac action potential (AP) and control the heartbeat. Dysfunction of these channels, due to genetic mutations, transcriptional or post-translational modifications, may disturb the AP and lead to arrhythmia, a major risk for CVD patients.
View Article and Find Full Text PDFBackground: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension.
Methods: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years).
Lymph nodes (LNs) are always embedded in the metabolically-active white adipose tissue (WAT), whereas their functional relationship remains obscure. Here, we identify fibroblastic reticular cells (FRCs) in inguinal LNs (iLNs) as a major source of IL-33 in mediating cold-induced beiging and thermogenesis of subcutaneous WAT (scWAT). Depletion of iLNs in male mice results in defective cold-induced beiging of scWAT.
View Article and Find Full Text PDFBrachial plexus root avulsion (BPRA) is frequently caused by high-energy trauma including traffic accident and birth trauma, which will induces massive motoneurons (MNs) death as well as loss of motor and sensory function in the upper limb. The death of MNs is attributed to energy deficiency, neuroinflammation and oxidative stress at the injured ventral horn of spinal cord triggered by BPRA injury. It has been reported which aldose reductase (AR), an endogenous enzyme that catalyzes fructose synthesis, positively correlates with the poor prognosis following cerebral ischemic injury, diabetic retinopathy and diabetic peripheral neuropathy.
View Article and Find Full Text PDFBackground: Gut microbiota (GM) dysregulation, known as dysbiosis, has been proposed as a crucial driver of obesity associated with "Western" diet (WD) consumption. Gut dysbiosis is associated with increased gut permeability, inflammation, and insulin resistance. However, host metabolic pathways implicated in the pathophysiology of gut dysbiosis are still elusive.
View Article and Find Full Text PDFBackground: Nutritional status affects the health of the public and is one of the key factors influencing social-economic development. To date, little research on the nutritional status of the Macao university student population has been conducted.
Objectives: To identify and evaluate the dietary pattern and the nutritional intake among Macao university students.
Retinopathy of prematurity (ROP) is a common cause of blindness in preterm babies. As a hypoxia-induced eye disease characterized by neovascularization, its association with retinal microglia has been noted but not well documented. We performed a comprehensive analysis of retinal microglia and retinal vessels in mouse oxygen-induced retinopathy (OIR), an animal model of ROP.
View Article and Find Full Text PDFBackground: Oxidative stress plays an important role in the pathology of ischemic stroke. Studies have confirmedthat scutellarin has antioxidant effects against ischemic injury, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism.
Methods: C57BL/6N mice (Wild-type, WT) and AR knockout (AR) mice suffered from transient middle cerebral artery occlusion (tMCAO) injury (1 h occlusion followed by 3 days reperfusion), and scutellarin was administered from 2 h before surgery to 3 days after surgery.
Investigation of the polysaccharides from an edible marine brown algae has led to obtaining three fractional sulfated polysaccharides UPPs 1-3 with molecular weights of 7.212 kDa, 13.924 kDa, and 55.
View Article and Find Full Text PDFThe current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC-MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 μg/kg) and 2-methylfuran (100%, 2-29639 μg/kg) were the compounds with the highest concentrations and detection rates in coffee products.
View Article and Find Full Text PDF