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Cinnamon is one of the world's oldest and most popular spices, and is derived from the inner bark of several tree species from the genus Cinnamomum. During the last two decades, cinnamon has demonstrated beneficial metabolic effects not only in animal experiments but also in clinical trials. Even recent meta-analyses have shown the protective effects of cinnamon on different components of metabolic syndrome and their complications. In the last 5 years, several experimental studies have unraveled the intricate molecular mechanisms underlying the antihypertensive, antihyperglycemic, lipid-lowering, weight-lowering, and cardioprotective properties of cinnamon. This review paper will discuss how cinnamon and its active components, particularly cinnamaldehyde, suppress inflammation and oxidative stress, modulate mitochondrial dysfunction, and regulate glucose uptake, insulin resistance, lipogenesis, beta-oxidation, Ca2+ signaling, and other cellar events at the molecular level. Specifically, we will delve into the molecular mechanisms involved in the metabolic effects of cinnamon to provide a deeper insight into how cinnamon can bring such beneficial effects. This review hopes to encourage the use of cinnamon in clinical settings, guide the combination of cinnamon with other drugs used to treat different components of metabolic syndrome based on their mechanism of action, and support the concept of complementary medicine for metabolic diseases. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)–like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. Methods: A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results: Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme‐linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin‐eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and Aβ protein accumulation in AD mice. Western blot validated protein expression in the Kelch‐like ECH‐associated protein 1 (Keap1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/HO‐1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO‐1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO‐1, caspase‐3, Bcl‐2, and Bax proteins in the Keap1/Nrf2/HO‐1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Conclusion: Quercetin can improve cognitive impairment and AD‐like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO‐1 pathway and reduction of cell apoptosis. [ABSTRACT FROM AUTHOR]

Aim: Blood–brain barrier (BBB) disorder is one of the early findings in cognitive impairments. We have recently found that Porphyromonas gingivalis bacteraemia can cause cognitive impairment and increased BBB permeability. This study aimed to find out the possible key virulence factors of P. gingivalis contributing to the pathological process. Materials and Methods: C57/BL6 mice were infected with P. gingivalis or gingipains or P. gingivalis lipopolysaccharide (P. gingivalis LPS group) by tail vein injection for 8 weeks. The cognitive behaviour changes in mice, the histopathological changes in the hippocampus and cerebral cortex, the alternations of BBB permeability, and the changes in Mfsd2a and Cav‐1 levels were measured. The mechanisms of Ddx3x‐induced regulation on Mfsd2a by arginine‐specific gingipain A (RgpA) in BMECs were explored. Results: P. gingivalis and gingipains significantly promoted mice cognitive impairment, pathological changes in the hippocampus and cerebral cortex, increased BBB permeability, inhibited Mfsd2a expression and up‐regulated Cav‐1 expression. After RgpA stimulation, the permeability of the BBB model in vitro increased, and the Ddx3x/Mfsd2a/Cav‐1 regulatory axis was activated. Conclusions: Gingipains may be one of the key virulence factors of P. gingivalis to impair cognition and enhance BBB permeability by the Ddx3x/Mfsd2a/Cav‐1 axis. [ABSTRACT FROM AUTHOR]

This study aims to investigate the mechanism of the anti‐atherosclerosis effect of Huayu Qutan Recipe (HYQT) on the inhibition of foam cell formation. In vivo, the mice were randomly divided into three groups: CTRL group, MOD group and HYQT group. The HYQT group received HYQT oral administration twice a day (20.54 g/kg/d), and the plaque formation in ApoE−/− mice was observed using haematoxylin–eosin (HE) staining and oil red O (ORO) staining. The co‐localization of aortic macrophages and lipid droplets (LDs) was examined using fluorescent labelling of CD11b and BODIPY fluorescence probe. In vitro, RAW 264.7 cells were exposed to 50 μg/mL ox‐LDL for 48 h and then treated with HYQT for 24 h. The accumulation of LDs was evaluated using ORO and BODIPY. Cell viability was assessed using the CCK‐8 assay. The co‐localization of LC3b and BODIPY was detected via immunofluorescence and fluorescence probe. LysoTracker Red and BODIPY 493/503 were used as markers for lysosomes and LDs, respectively. Autophagosome formation were observed via transmission electron microscopy. The levels of LC3A/B II/LC3A/B I, p‐mTOR/mTOR, p‐4EBP1/4EBP1, p‐P70S6K/P70S6K and TFEB protein level were examined via western blotting, while SQSTM1/p62, Beclin1, ABCA1, ABCG1 and SCARB1 were examined via qRT‐PCR and western blotting. The nuclear translocation of TFEB was detected using immunofluorescence. The components of HYQT medicated serum were determined using Q‐Orbitrap high‐resolution MS analysis. Molecular docking was employed to identify the components of HYQT medicated serum responsible for the mTOR signalling pathway. The mechanism of taurine was illustrated. HYQT has a remarkable effect on atherosclerotic plaque formation and blood lipid level in ApoE−/− mice. HYQT decreased the co‐localization of CD11b and BODIPY. HYQT (10% medicated serum) reduced the LDs accumulation in RAW 264.7 cells. HYQT and RAPA (rapamycin, a mTOR inhibitor) could promote cholesterol efflux, while chloroquine (CQ, an autophagy inhibitor) weakened the effect of HYQT. Moreover, MHY1485 (a mTOR agonist) also mitigated the effects of HYQT by reduced cholesterol efflux. qRT‐PCR and WB results suggested that HYQT improved the expression of the proteins ABCA1, ABCG1 and SCARB1.HYQT regulates ABCA1 and SCARB1 protein depending on the mTORC1/TFEB signalling pathway. However, the activation of ABCG1 does not depend on this pathway. Q‐Orbitrap high‐resolution MS analysis results demonstrated that seven core compounds have good binding ability to the mTOR protein. Taurine may play an important role in the mechanism regulation. HYQT may reduce cardiovascular risk by promoting cholesterol efflux and degrading macrophage‐derived foam cell formation. It has been observed that HYQT and ox‐LDL regulate lipophagy through the mTOR/TFEB signalling pathway, rather than the mTOR/4EBP1/P70S6K pathway. Additionally, HYQT is found to regulate cholesterol efflux through the mTORC1/TFEB/ABCA1‐SCARB1 signal axis, while taurine plays a significant role in lipophagy. [ABSTRACT FROM AUTHOR]

The aim of this study is to examine the long-term effects of prenatal and early-life WIFI signal exposure on neurodevelopment and behaviors as well as biochemical alterations of Wistar rats. On the first day of pregnancy (E0), expectant rats were allocated into two groups: the control group (n = 12) and the WiFi-exposed group (WiFi group, n = 12). WiFi group was exposed to turn on WiFi for 24 h/day from E0 to postnatal day (PND) 42. The control group was exposed to turn-off WiFi at the same time. On PND7-42, we evaluated the development and behavior of the offspring, including body weight, pain threshold, and swimming ability, spatial learning, and memory among others. Also, levels of proteins involved in apoptosis were analyzed histologically in the hippocampus in response to oxidative stress. The results showed that WiFi signal exposure in utero and early life (1) increased the body weight of WiFi + M (WiFi + male) group; (2) no change in neuro-behavioral development was observed in WiFi group; (3) increased learning and memory function in WiFi + M group; (4) enhanced comparative levels of BDNF and p-CREB proteins in the hippocampus of WiFi + M group; (5) no neuronal loss or degeneration was detected, and neuronal numbers in hippocampal CA1 were no evidently differences in each group; (6) no change in the apoptosis-related proteins (caspase-3 and Bax) levels; and (7) no difference in GSH-PX and SOD activities in the hippocampus. Prenatal WiFi exposure has no effects on hippocampal CA1 neurons, oxidative equilibrium in brain, and neurodevelopment of rats. Some effects of prenatal WiFi exposure are sex dependent. Prenatal WiFi exposure increased the body weight, improved the spatial memory and learning function, and induced behavioral hyperactivity of male rats. [ABSTRACT FROM AUTHOR]

Background: A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia.Methods: Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs.Results: Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis.Conclusions: Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required. [ABSTRACT FROM AUTHOR]

Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population with high self-renewal ability that originates from the cranial neural crest. Since SHED are homologous to the central nervous system, they possess superior capacity to differentiate into neural cells. However, whether and how SHED ameliorate degenerative central nervous disease are unclear. Chronic cerebral ischemia (CCI) is a kind of neurological disease caused by long-term cerebral circulation insufficiency and is characterized by progressive cognitive and behavioral deterioration. In this study, we showed that either systemic transplantation of SHED or SHED infusion into the hippocampus ameliorated cognitive impairment of CCI rats in four weeks after SHED treatment by rescuing the number of neurons in the hippocampus area. Mechanistically, SHED transplantation decreased the apoptosis of neuronal cells in the hippocampus area of CCI rats through downregulation of cleaved caspase-3. In summary, SHED transplantation protected the neuronal function and reduced neuronal apoptosis, resulting in amelioration of cognitive impairment from CCI. Our findings suggest that SHED are a promising stem cell source for cell therapy of neurological diseases in the clinic. [ABSTRACT FROM AUTHOR]

For the first time, a simple and validated reversed-phase liquid chromatography (RP-LC) with fluorescence detection has been developed for the simultaneous analysis of glutamate (Glu), γ-aminobutyric acid (GABA), glycine (Gly) and taurine (Tau) in Wistar and tremor rats brain synaptosomes. The samples were separated on a C18 analytical column with gradient elution of methanol and 0.1 mol L potassium acetate at a flow rate of 1 mL min. Total run time was approximately 25 min. All calibration curves exhibited good linearity ( r > 0.999) within test ranges. The reproducibility was estimated by intra-and inter-day assays and RSD values were less than 2.48%. The recoveries were between 96.32 and 105.21%. The method was successfully applied to the quantification of amino acids in Wistar and tremor rats brain synaptosomes. Through this developed protocol, the levels of Glu in hippocampal and prefrontal cortical synaptosomes of tremor rats were both significantly elevated than those of adult Wistar rats whereas significantly decreased concentrations of GABA and Gly were observed in the hippocampal region of tremor rats without evident difference in the prefrontal cortex between experimental and control groups. In addition, our studies also showed a marked elevation of Tau in tremor rats hippocampal synaptosomes although there was no pronounced difference in the prefrontal cortical region of Wistar and tremor rats. [ABSTRACT FROM AUTHOR]