Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer’s disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, Ganoderma lucidum, for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D-galactose to induce accelerated aging showed that alcohol extracts of G. lucidum contained the main active anti-aging extract. The effects on DNA methylation of these G. lucidum extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from G. lucidum. Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of G. lucidum, including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that G. lucidum alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ1-42. We concluded that alcohol extracts from G. lucidum, including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer’s Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis

Gut microbiota influences the central nervous system disorders such as Alzheimer’s disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology

Electrocatalytic Water Oxidation by a Water-Soluble Nickel Porphyrin Complex at Neutral pH with Low Overpotential

The water-soluble cationic nickel­(II) complex of <i>meso</i>-tetrakis­(4-<i>N</i>-methylpyridyl)­porphyrin (<b>1</b>) can electrocatalyze water oxidation to O₂ in neutral aqueous solution (pH 7.0) with the onset of the catalytic wave appearing at ∼1.0 V (vs NHE). The homogeneous catalysis with <b>1</b> was verified. Catalyst <b>1</b> exhibited water oxidation activity in a pH range 2.0–8.0 and had a strict linear dependence of catalytic current on its concentration. After 10 h of constant potential electrolysis at 1.32 V (vs NHE), a negligible difference of the solution was observed by UV–vis. In addition, inspection of the working electrode by electrochemistry, scanning electron microscope (SEM), and energy dispersive X-ray spectroscopy (EDX) showed no sign of deposition of NiO_<i>x</i> films. These results strongly argued that <b>1</b> is a real molecular electrocatalyst for water oxidation. The turnover frequency (TOF) for this process was 0.67 s^–1 at 20 °C. On the basis of results from the kinetic isotope effect (KIE) and inhibition experiments, electrochemical studies in various buffer solutions with different anions and pHs, and DFT calculations, a catalytic cycle of <b>1</b> for water oxidation via a formally Ni­(IV) species was proposed

Novel PRKAR1A mutation in Carney complex: a case report and literature review

ObjectiveCarney complex is a rare autosomal dominant syndrome that has been shown to be associated with inactivation due to PRKAR1A mutations. We revealed a novel PRKAR1A gene mutation in Chinese patient with Carney complex and review the literature to enhance understanding of Carney complex.Case presentationA 23-year-old Chinese male patient with a family history cardiac myxoma was admitted to our Department of Endocrinology because of central obesity and hyperpigmentation. Physical examination revealed a maximum blood pressure of 150/93mmHg, a waist circumference of 102cm, a weight of 70kg, a height of 170cm, and a BMI of 24.22kg/m2. Additionally, there was spotty skin pigmentation on the lip mucosa, purple striae on the abdomen, thin skin on both legs, and visible veins. Blood examination revealed hypercortisolemia, decreased adrenocorticotropic hormone (ACTH) levels and failure to suppress cortisol with low and high-dose dexamethasone suppression tests. Magnetic resonance imaging (MRI) scan revealed multiple small adrenal nodules and Retroperitoneal neurogenic tumor. Genetic testing showed a novel heterozygous mutation in exon 5 of PRKAR1A (c.500_502 + 8delAAGGTAAGGGC). The patient underwent resection of the right adrenal gland and retroperitoneal neoplasms in 2020. Postoperative pathology following the right adrenal gland resection showed nodular hyperplasia of the adrenal cortex. The pathology from the retroperitoneal tumor resection revealed spindle cell tumors rich in pigment and cells. The patient was diagnosed as Carney complex according to Stratakis CA in 2001 guidelines. After long-term follow-up, the patient’s condition was stable, with weight loss, waist circumference reduction, significantly lower cortisol levels, and normal blood lipids.ConclusionThis case reported a Carney complex in a Chinese patient, characterized clinically by non-ACTH-dependent Cushing’s syndrome, familial recurrent cardiac myxomas, psammomatous melanotic schwannoma (PMS) and skin and mucosal pigmentation. A novel subtype of PRKAR1A mutation was discovered, which may affect the characteristics of the PRKAR1A protein and contribute to the development of Carney complex

Maternal Caffeine Consumption during Pregnancy and Risk of Low Birth Weight: A Dose-Response Meta-Analysis of Observational Studies

Epidemiologic studies have shown inconsistent conclusions about the effect of caffeine intake during pregnancy on the risk of low birth weight (LBW). We performed a meta-analysis and linear-dose response analysis examining the association between caffeine consumption during pregnancy and risk of LBW. PubMed and EMBASE were searched for relevant articles published up to March 2014. Eight cohort and four case-control studies met all inclusion criteria. Using a random-effects model of the twelve studies, the pooled odds ratio (OR) for the risk of LBW comparing the highest versus lowest level of caffeine intake during pregnancy was 1.38 (95% CI: 1.10, 1.73). Linear dose-response analysis showed that every additional 100 mg of caffeine intake (1 cup of coffee or 2 cups of tea) per day during pregnancy was associated with a 3.0% increase in OR for LBW. There was a moderate level of overall heterogeneity with an I-squared value of 55% (95% CI: 13, 76%), and no evidence of publication bias based on Egger’s test (P = 0.20) and the funnel plot. Thus, high caffeine intake during pregnancy is associated with a significant increase in the risk of LBW, and this risk appears to increase linearly as caffeine intake increases

Effects of Oligosaccharides From Morinda officinalis on Gut Microbiota and Metabolome of APP/PS1 Transgenic Mice

Alzheimer's disease (AD), a progressive neurodegenerative disorder, lacks preclinical diagnostic biomarkers and therapeutic drugs. Thus, earlier intervention in AD is a top priority. Studies have shown that the gut microbiota influences central nervous system disorders and that prebiotics can improve the cognition of hosts with AD, but these effects are not well understood. Preliminary research has shown that oligosaccharides from Morinda officinalis (OMO) are a useful prebiotic and cause substantial memory improvements in animal models of AD; however, the mechanism is still unclear. Therefore, this study was conducted to investigate whether OMO are clinically effective in alleviating AD by improving gut microbiota. OMO were administered to APP/PS1 transgenic mice, and potential clinical biomarkers of AD were identified with metabolomics and bioinformatics. Behavioral experiments demonstrated that OMO significantly ameliorated the memory of the AD animal model. Histological changes indicated that OMO ameliorated brain tissue swelling and neuronal apoptosis and downregulated the expression of the intracellular AD marker Aβ1−42. 16S rRNA sequencing analyses indicated that OMO maintained the diversity and stability of the microbial community. The data also indicated that OMO are an efficacious prebiotic in an animal model of AD, regulating the composition and metabolism of the gut microbiota. A serum metabolomics assay was performed using UHPLC-LTQ Orbitrap mass spectrometry to delineate the metabolic changes and potential early biomarkers in APP/PS1 transgenic mice. Multivariate statistical analysis showed that 14 metabolites were significantly upregulated, and 8 metabolites were downregulated in the model animals compared to the normal controls. Thus, key metabolites represent early indicators of the development of AD. Overall, we report a drug and signaling pathway with therapeutic potential, including proteins associated with cognitive deficits in normal mice or gene mutations that cause AD

Linear dose-response analysis on the effect of caffeine intake during pregnancy on low birth weight.

<p>Linear dose-response analysis on the effect of caffeine intake during pregnancy on low birth weight.</p

Literature search results for publications related to caffeine consumption during pregnancy and risk of low birth weight.

<p>Literature search results for publications related to caffeine consumption during pregnancy and risk of low birth weight.</p