Effects of Fu brick tea polysaccharides on gut microbiota and fecal metabolites of HFD/STZ-induced type 2 diabetes rats.

The prevalence of type 2 diabetes mellitus (T2DM) has dramatically increased globally, and the antidiabetic effects and underlying mechanisms of the polysaccharides extracted from Fu brick tea (FBTP) were investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM rats. Administration of FBTP at 200 and 400 mg per kg bw significantly relieved dyslipidemia (i.e. TC, TG, LDL-C and HDL-C), insulin resistance (IR) and pancreas oxidative stress (i.e. CAT and GSH-Px) in T2DM rats. Mechanistically, FBTP rescued the HFD/STZ-induced alterations in the abundance of Bacteroidota, Actinobacteriota, Proteobacteria and Firmicutes. At the genus level, FBTP notably increased the abundance of Ruminococcus, Lactobacillus and Lachnospiraece_NK4A136_group, but reduced the population of Prevotella and Faecalibaculum in T2DM rats. FBTP also significantly elevated colonic short-chain fatty acid (SCFAs) levels. Moreover, apparent changes in amino acid absorption and metabolism were observed upon FBTP intervention. These findings suggested that FBTP might alleviate T2DM by reshaping the gut microbiota and regulating intestinal metabolites.

Theabrownin from Fu Brick Tea Improves Ulcerative Colitis by Shaping the Gut Microbiota and Modulating the Tryptophan Metabolism.

Fu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.

Fu Brick Tea Polysaccharides Prevent Obesity via Gut Microbiota-Controlled Promotion of Adipocyte Browning and Thermogenesis.

The antiobesity efficacy and underlying mechanisms of polysaccharides extracted from Fu brick tea (FBTP) were investigated. An 8-week administration of FBTP dose-dependently inhibited increases in body weight and weights of the epididymal-, retroperitoneal- and inguinal-white adipose tissues and stimulated beige-fat development and brown adipose tissue-derived nonshivering thermogenesis in high-fat diet-induced obese mice. FBTP protected against obesity-associated abnormality in serum adiponectin and leptin, indicating its positive regulation of energy metabolism. FBTP reversed gut dysbiosis by enriching beneficial bacteria, for example, Lactobacillus, Parabacteroides, Akkermansia, Bifidobacterium, and Roseburia. Results from the fecal microbiota transplantation further confirmed that FBTP-induced microbial shifts contributed to adipose browning and thermogenesis, thereby alleviating host adiposity, glucose homeostasis, dyslipidemia, and its related hepatic steatosis. Our study demonstrates the great potential of FBTP with prebiotic-like activities in preventing diet-induced obesity and its related metabolic complications via gut microbiota-derived enhancement of fat burning and energy expenditures.

Fu Brick Tea Manages HFD/STZ-Induced Type 2 Diabetes by Regulating the Gut Microbiota and Activating the IRS1/PI3K/Akt Signaling Pathway.

The antidiabetic effects of Fu brick tea aqueous extract (FTE) and its underlying molecular mechanism in type 2 diabetes mellitus (T2DM) mice were investigated. FTE treatment significantly relieved dyslipidemia, insulin resistance (IR), and hepatic oxidative stress caused by T2DM. FTE also ameliorated the T2DM-induced gut dysbiosis by decreasing the Firmicutes/Bacteroidota (F/B) ratio at the phylum level and promoting the proliferation of Bifidobacterium, Parabacteroides, and Roseburia at the genus level. Besides, FTE significantly improved colonic short-chain fatty acid levels of T2DM mice. Furthermore, the antidiabetic effects of FTE were proved to be mediated by the IRS1/PI3K/Akt and AMPK-mediated gluconeogenesis signaling pathways. Metabolomics analysis illustrated that FTE recovered the levels of 28 metabolites associated with T2DM to the levels of normal mice. Taken together, these findings suggest that FTE can alleviate T2DM by reshaping the gut microbiota, activating the IRS1/PI3K/Akt pathway, and regulating intestinal metabolites.

Real-World Experience with Artificial Intelligence-Based Triage in Transferred Large Vessel Occlusion Stroke Patients.

BACKGROUND AND PURPOSE: Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes. METHODS: A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts. RESULTS: The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; p = 0.01) with less variation (p < 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (p = 0.15). CONCLUSIONS: Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

High l-Carnitine Ingestion Impairs Liver Function by Disordering Gut Bacteria Composition in Mice.

This article studied the effects of high l-carnitine consumption on intestinal microbiota, liver function, and metabolite distribution in mice. 16S rRNA results showed that high l-carnitine supplementation could induce the accumulation of Anaerobiospirillum, Coriobacteriaceae, Akkermansia_muciniphila, and Helicobacter. High intake of l-carnitine also induced liver injury, which was proved by the increases in the serum AST and ALT activities, production of inflammatory liver cytokines (IL-1, IL-6, TNF-α, and TNF-ß), lipid metabolism (TC, TG, HDL, and LDL) disorder, and decline in antioxidant ability (SOD, GSH-Px, MDA, and RAHFR). The correlation analysis results showed that Anaerobiospirillum, Akkermansia_muciniphila, and Helicobacter were strongly positively correlated with AST, IL-1, TNF-α, TNF-ß, and MDA levels (r > 0.5, p < 0.01 or p < 0.05). All in all, high l-carnitine ingestion could induce a decline in the liver function by disorder in the gut bacteria composition, resulting in an increase in TMAO metabolism.

Decaisnea insignis Seed Oil Inhibits Trimethylamine-N-oxide Formation and Remodels Intestinal Microbiota to Alleviate Liver Dysfunction in l-Carnitine Feeding Mice.

Elevated circulating level of the intestinal microbiota-derived l-carnitine metabolite trimethylamine-N-oxide (TMAO) has recently been linked to many chronic diseases. The purpose of our study was to investigate the effects of omega-7-enriched Decaisnea insignis seed oil (DISO) on reducing TMAO formation to prevent the l-carnitine-induced hepatic damage in mice. Feeding of mice with 3% l-carnitine in drinking water clearly increased the serum and urinary levels of TMAO (p < 0.05 vs Normal), whereas the serum and urinary TMAO formation was sharply reduced by DISO administration (p < 0.05). Meanwhile, DISO resulted in strong inhibition against the elevation of hepatic injury marker (AST, ALT, and ALP) activities and dyslipidemia (TC, TG, LDL-C, and HDL-C), as well as liver inflammatory cytokine (IL-1, IL-6, TNF-α, and TNF-ß) release in l-carnitine-fed mice (p < 0.05). As revealed by 16S rDNA gene sequencing, DISO significantly inhibited the l-carnitine-induced elevations in the abundance of Firmicutes, Proteobacteria, and Erysipelotrichaceae and the increases in the proportion of Lactobacillus and Akkermansia, revealing that DISO attenuated the l-carnitine-caused gut dysbiosis. These findings suggested that DISO could alleviate liver dysfunction in l-carnitine-fed mice, which might be due to the protection against TMAO formation by modulating the gut microbiota.

Effects of music therapy on anxiety and physiologic parameters in angiography: a systematic review and meta-analysis.

BACKGROUND: Given the anxiety patients experience during angiography, evidence supporting the efficacy of music therapy during these angiographic procedures is potentially of clinical value. OBJECTIVE: To analyze the existing literature forthe use of music therapy during cerebral, coronary, and peripheral angiography to determine whether it improves patient anxiety levels, heart rate, and blood pressure during the procedure. METHODS: PubMed, Embase, and Scopus were searched to identify studies of interest. Inclusion criteria included studies reporting using music therapy in either cerebral, coronary, or peripheral angiography. Studies focused on a pediatric population; animal studies and case reports were excluded. Participant demographics, interventions, and outcomes were collected by two study authors. Bias and study quality of randomized controlled trials (RCTs) were assessed using the Cochrane Risk of Bias Tool. Separate meta-analyses of the RCTs were performed to compare State Trait Anxiety Inventory (STAI), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) in the music intervention group versus control group. Heterogeneity was determined by calculating I2 values, and a random-effects model was used when heterogeneity exceeded 50%. RESULTS: The preprocedure to postprocedure improvement in STAI was significantly greater in the experimental group than the control group (p=0.004), while the decrease in HR, SBP, and DBP was not significant. CONCLUSIONS: Recorded music and/or music therapy in angiography significantly decreases patients' anxiety levels, while it has little to no effect on HR and BP. This meta-analysis is limited by the relatively few RCTs published on this subject. PROSPERO REGISTRATION NUMBER: CRD42018099103.

The Prophylactic and Therapeutic Effects of Fermented Cordyceps sinensis Powder, Cs-C-Q80, on Subcortical Ischemic Vascular Dementia in Mice.

Corbrin Capsule, a preparation of Cordyceps sinensis analogue, is a pleiotropic traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The neuroprotective effects of Cs-C-Q80, as a substitution of Cordyceps sinensis, have not been fully identified. The objectives of this study were to explore the prophylactic and therapeutic effects of Cs-C-Q80 in vascular dementia mice model. The efficacy of Cs-C-Q80 was investigated in a molecular level as well. The subcortical ischemic vascular dementia was modelled by permanent right unilateral common carotid arteries occlusion (rUCCAO) in adult male mice. The animals were randomly divided and treated by gavage with vehicle (1% CMC-Na solution) (rUCCAO model) or Cs-C-Q80 powder at 0.2 g/kg or 1.0 g/kg, respectively. Preventive treatment was administrated by gavage daily for 7 days before rUCCAO, while therapeutic treatment was administrated continuously from 28 days after rUCCAO. Object recognition test and Morris water maze test were performed to evaluate the learning and working memory. The luxol fast blue stain (Kluver-Barrera method) and immunohistochemistry for myelin basic protein (MBP) were employed to determine the severity of white matter damage. Both preventive and therapeutic treatment with Cs-C-Q80 protected against the rUCCAO-induced memory impair in mice as determined by object recognition and Morris water maze tests. The histopathological analyses revealed significant white matter rarefaction and reduction of MBP expression in corpus callosum after rUCCAO, which could be counteracted by either preventive or therapeutic treatment with Cs-C-Q80. Moreover, the Cs-C-Q80 treatments inhibited rUCCAO-induced astrocytes activation and the tumor necrosis factor α (TNF-α) and interleukin-1ß expression, indicating the anti-inflammatory roles of Cs-C-Q80 against subcortical ischemia. Cs-C-Q80 is a potential preparation for the prophylaxis and treatment of subcortical ischemic vascular dementia. The underlying pharmacological efficacy might be associated with suppression of myelin degeneration, glia activation, and inflammatory cytokines release.

Effect of acetazolamide and gingko biloba on the human pulmonary vascular response to an acute altitude ascent.

Acetazolamide and gingko biloba are the two most investigated drugs for the prevention of acute mountain sickness (AMS). Evidence suggests that they may also reduce pulmonary artery systolic pressure (PASP). To investigate whether these two drugs for AMS prevention also reduce PASP with rapid airlift ascent to high altitude, a randomized controlled trial was conducted on 28 healthy young men with acetazolamide (125 mg bid), gingko biloba (120 mg bid), or placebo for 3 days prior to airlift ascent (397 m) and for the first 3 days at high altitude (3658 m). PASP, AMS, arterial oxygen saturation (Sao2), mean arterial pressure (MAP), heart rate (HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were assessed both at 397 m and 3658 m. HR, PEF, and PASP increased with altitude exposure (p<0.05), and SaO2 decreased (p<0.05). PASP with acetazolamide (mean at 3658 m, 26.2 mm Hg; incremental change, 4.7 mm Hg, 95% CI., 2.6-6.9 mm Hg) was lower than that with ginkgo biloba (mean at 3658 m, 33.7 mm Hg, p=0.001; incremental change, 13.1 mm Hg, 95%CI., 9.6-16.5 mm Hg, p=0.002), and with placebo (mean at 3658 m, 34.7 mm Hg, p<0.001; 14.4 mm Hg, 95% CI., 8.8-20.0 mm Hg, p=0.001). The data show that a low prophylactic dosage of acetazolamide, but not gingko biloba, mitigates the early increase of PASP in a quick ascent profile.

Chronic h1-antihistamine treatment increases seizure susceptibility after withdrawal by impairing glutamine synthetase.

AIM: To investigate the effect of chronic H1-antihistamine treatment on seizure susceptibility after drug withdrawal in nonepileptic rats and to further study its relation to glutamine synthetase (GS), which is the key enzyme for glutamate metabolism and gamma aminobutyric acid (GABA) synthesis. METHODS: After drug withdrawal from a 2-week treatment with diphenhydramine or pyrilamine, seizure susceptibility was determined by amygdaloid kindling or pentylenetetrazol model; meanwhile, the GS expression or activity was analyzed. The glutamine, glutamate, and GABA contents were measured by high-performance liquid chromatography. RESULTS: Seizure susceptibility significantly increased in amygdaloid kindling and pentylenetetrazol model 10 days after drug withdrawal from a 2-week treatment with H1-antihistamines. Meanwhile, GS activity and expression in the cortex or hippocampus decreased simultaneously with a marked decline of glutamine and GABA content. Comparable inhibition of GS activity by methionine sulfoximine was also sufficient to increase the susceptibility, while supplementation with glutamine reversed the high susceptibility 10 days after diphenhydramine withdrawal. Moreover, the seizure susceptibility increased 10 days after diphenhydramine withdrawal in wild-type mice but not in histidine decarboxylase knockout mice, which lack histamine. CONCLUSIONS: Chronic H1-antihistamine treatment produces long-lasting increase in seizure susceptibility in nonepileptic rodents after drug withdrawal and its mechanism involves impairment of GS through blocking the action of histamine.

Dietary vitamin E, brain redox status and expression of Alzheimer's disease-relevant genes in rats.

Oxidative stress is one of the major pathological features of Alzheimer's disease (AD). Here, we investigated whether dietary vitamin E (VE) depletion may induce adverse effects and supplementation with alpha-tocopherol (alphaT) may result in beneficial effects on redox status and the regulation of genes relevant in the pathogenesis of AD in healthy rats. Three groups of eight male rats each were fed diets with deficient ( < 1 mg alphaT equivalents/kg diet), marginal (9 mg alphaT equivalents/kg diet) or sufficient (18 mg alphaT equivalents/kg diet) concentrations of natural-source VE for 6 months; a fourth group was fed the VE-sufficient diet fortified with alphaT (total VE, 146 mg alphaT equivalents/kg diet). Feeding of the experimental diets dose dependently altered alphaT concentrations in the cortex and plasma. No significant changes in F2-isoprostane concentrations, activities of antioxidative enzymes (total superoxide dismutase, Se-dependent glutathione peroxidase) and concentrations of glutathione or the expression of AD-relevant genes were observed. In this non-AD model, depletion of VE did not induce adverse effects and supplementation of alphaT did not induce positive effects on the parameters related to the progression of AD.

[Directed differentiation of mouse embryonic stem cells into neuronal cells induced by icaritin in vitro].

OBJECTIVE: To evaluate the inductive effects of icaritin (ICT) on the directed differentiation of mouse embryonic stem (ES) cells into neuronal cells in vitro. METHODS: ES cells were cultured with embryoid body (EB) formation cultures, ICT in different concentrations was added in the cultural media and the cells were harvested in several differentiation phases. The expression spectrums of neuronal cell-specific genes and proteins were verified by semi-quantitative RT-PCR and immunocytochemistry analysis, respectively. RESULTS: Differentiation of neurocyte phenotype from ES cells was promoted by ICT in a concentration-and time-dependent manner. ICT at 10(-7)mol/L significantly enhanced the differentiation toward neuronal cells, and up to 80 % of EBs outgrowth in d 8+8 incubation. The gene expressions of beta-tubulin III in neuron and GFAP in glial cells were detected in neuronal cell phenotype derived from EBs. Furthermore, nestin was detected in precursor cells, beta-tubulin III and GFAP were detected in the generated precursor neurocytes immunocytochemically. CONCLUSION: Directed differentiation of neurons is facilitated by ICT in EB formation culture, which is associated with the expression of developmental-dependent gene and protein.

[Protective effect of icaritin on apoptosis of primarily cultured rat neurons induced by Abeta25-35 peptide].

OBJECTIVE: To investigate the protective effects of icaritin (ICT) on apoptosis of primarily cultured rat neurons induced by Abeta(25-35) peptide and its mechanism. METHODS: Cortical neurons from rat embryonic cortical on d17 pregnancy were cultured in neural basal medium for 7 days. Icaritin (ICT) was pre-incubated for 24 h before adding Abeta(25-35) peptide and then the cells were incubated for 72 h. Neuroprotective effects of ICT were evaluated by MTT assay, LDH level in medium and cell morphological observation. Meanwhile, apoptosis was determined by JC-1 staining for mitochondria membrane potential (DeltaPsim) and AO/EB double staining for genetic damage of nucleoli in monolayer cells. RESULTS: 0.1 micromol.L(-1) ICT pre-incubation for 24 h prevented rat neurons from Abeta(25-35) peptide induced apoptosis significantly as demonstrated by MTT, LDH assay and morphological observation. AO/EB double staining also indicated that ICT prevented neurons from apoptosis. JC-1 staining further showed that ICT prevented decreasing of mitochondrial DeltaPsim induced by Abeta(25-35) peptide. CONCLUSION: ICT could protect primarily cultured rat neurons from Abeta(25-35) peptide induced apoptosis.