OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

Humans ; Gastrointestinal Microbiome ; Atherosclerosis ; Methylamines/metabolism*

The main cause of death in patients with end-stage renal disease (ESRD) is cardiovascular disease, and trimethylamine-N-oxide (TMAO) has been found to be one of the specific risk factors in the pathogenic process in recent years. TMAO is derived from intestinal bacterial metabolism of dietary choline, carnitine and other substances and subsequently catalyzed by flavin monooxygenase enzymes in the liver. The changes of intestinal bacteria in ESRD patients have contributed to the accumulation of gut-derived uremic toxins such as TMAO, indoxyl sulfate and indole-3-acetic acid. While elevated TMAO concentration accelerates atherosclerosis through mechanisms such as inflammation, increased scavenger receptor expression, and inhibition of reverse cholesterol transport. In this review, this research introduces the biological function, metabolic processes of TMAO and mechanisms by which TMAO promotes the progression of cardiovascular disease in ESRD patients and summarizes current interventions that may be used to reverse gut microbiota disturbances, such as activated carbon, fecal microbial transplantation, dietary improvement, probiotic and probiotic introduction. It also focuses on exploring intervention targets to reduce the gut-derived uremic toxin TMAO in order to explore the possibility of more cardiovascular disease treatments for ESRD patients.
Cardiovascular Diseases ; Humans ; Kidney Failure, Chronic ; Methylamines ; Oxides ; Uremic Toxins

OBJECTIVE: To compare the clinical therapeutic effect on acute ischemic stroke between Naochang Tongtiao acupuncture (acupuncture for brain-gut homology) and conventional acupuncture, and to explore the possible mechanism. METHODS: A total of 64 patients with acute ischemic stroke were randomized into an observation group and a control group, 32 cases in each one. Basic western medical therapy was adopted in both groups. In the observation group, Naochang Tongtiao acupuncture was applied at anterior oblique line of vertex-temporal, Zhongwan (CV 12), Guanyuan (CV 4), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, conventional acupuncture was applied. The treatment was given once a day, 6 days a week for 3 weeks in both groups. Before and after treatment, National Institution of Health stroke scale (NIHSS) score, serum levels of interleukin-17 (IL-17) and hypersensitive C reactive protein (hs-CRP), and plasma level of trimethylamine oxide (TMAO) were compared in the two groups. RESULTS: After treatment, NIHSS scores, serum levels of IL-17 and hs-CRP, and plasma levels of TMAO were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.05). CONCLUSION Naochang Tongtiao acupuncture can improve the nerve function in patients with acute ischemic stroke, its therapeutic effect is superior to conventional acupuncture, the mechanism may relate to the regulation on inflammatory reaction and the level of intestinal flora metabolite.
Acupuncture Points ; Acupuncture Therapy ; Brain-Gut Axis ; C-Reactive Protein ; Humans ; Interleukin-17 ; Ischemic Stroke/therapy* ; Methylamines ; Stroke/therapy* ; Treatment Outcome

Objective: To explore the value of the assessment of plasma trimethylamine N-oxide (TMAO) combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the all-cause mortality, length of hospitalization, and hospital cost in ischemic heart failure (IHF) patients. Methods: This prospective cohort study included 189 patients (157 males, mean age (64.0±10.5) years) with a left ventricular ejection fraction<45% caused by coronary artery disease, who hospitalized in our department from March 2016 to December 2020. Baseline data, including demographics, comorbid conditions and laboratory examination, were analyzed. The cumulative rate of all-cause mortality was evaluated using the Kaplan-Meier method and compared between the groups according to the log-rank test. Relative risks were reported as hazard ratios (HR) and 95% confidence interval (95%CI) calculated using the Cox proportional-hazards analysis, with stepwise adjustment for covariables. Spearman correlation analysis was then performed to determine the relationship between TMAO combined with NT-proBNP and length of hospitalization and hospital cost. Results: There were 50 patients in the low TMAO+low NT-proBNP group, 89 patients in high TMAO or high NT-proBNP group, 50 patients in high TMAO+high NT-proBNP group. The mean follow-up period was 3.0 years. Death occurred in 70 patients (37.0%), 27 patients (54.0%) in high TMAO+high NT-proBNP group, 29 patients (32.6%) in high TMAO or high NT-proBNP group and 14 patients (28.0%) in low TMAO+low NT-proBNP group. TMAO, in combination with NT-proBNP, improved all-cause mortality prediction in IHF patients when stratified as none, one or both biomarker(s) elevation, with the highest risk of all-cause mortality in high TMAO+high NT-proBNP group (HR=3.62, 95%CI 1.89-6.96, P<0.001). ROC curve analysis further confirmed that TMAO combined with NT-proBNP strengthened the prediction performance on the risk of all-cause death (AUC=0.727(95%CI 0.640-0.813), sensitivity 55.0%, characteristic 83.1%). Spearman correlation analysis showed that IHF patients with high TMAO and high NT-proBNP were positively associated with longer duration of hospitalization (r=0.191,P=0.009), but not associated with higher hospital cost (r=0.030, P=0.686). Conclusions: TMAO combined with NT-proBNP are valuable prediction tool on risk stratification of patients with IHF, and those with two biomarkers elevation face the highest risk of mortality during follow-up period, and are associated with the longer hospital stay.
Aged ; Biomarkers/blood* ; Female ; Heart Failure/diagnosis* ; Hospitalization ; Humans ; Male ; Methylamines/blood* ; Middle Aged ; Natriuretic Peptide, Brain/blood* ; Peptide Fragments ; Prognosis ; Prospective Studies

The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine ; Choline/metabolism* ; Chronic Disease ; Heart Failure/genetics* ; Humans ; Methylamines ; Oxygenases ; Prospective Studies

Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.
Coronary Artery Disease ; Gastrointestinal Microbiome ; Humans ; Methylamines ; Oxides

Cardiovascular Diseases ; Gastrointestinal Microbiome ; Humans ; Methylamines

PURPOSE: The efficacy of periarticular multimodal drug injection and adductor canal block after a medial opening-wedge high tibial osteotomy was compared in terms of the postoperative pain level. MATERIALS AND METHODS: From November 2016 to March 2017, 60 patients underwent a medial opening-wedge high tibial osteotomy under spinal anesthesia. Preemptive analgesic medication, intravenous patient controlled anesthesia were used for pain control in all patients. Thirty patients received a periarticular multimodal drug injection (group I), and 30 patients received an adductor canal block (group II). These two groups were compared regarding the postoperative pain level, frequency of additional tramadol injections, total amount of patient-controlled analgesia, and number of times that the patients pushed the patient-controlled analgesia button at each time interval. RESULTS: The visual analogue scale scores over the two-week postoperative period showed no statistical significance. The frequency of additional tramadol hydrochloride injections was similar in the two groups over time. The mean number of times that patients pushed the patient-controlled analgesia button was similar in two groups over time. The total amount of patient-controlled analgesia was similar in the two groups over time. CONCLUSION: This study shows that intraoperative periarticular multimodal drug injections and adductor canal block may have a similar effect on postoperative pain control in patients who have undergone a medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee.
Analgesia, Patient-Controlled ; Anesthesia ; Anesthesia, Spinal ; Humans ; Knee ; Nerve Block ; Osteoarthritis ; Osteotomy ; Pain, Postoperative ; Postoperative Period ; Tramadol

BACKGROUND: The transversus abdominis plane (TAP) block is an effective technique to block the thoracolumbar nerves innervating the anterolateral abdominal wall. This study was conducted to evaluate the analgesic efficacy and opioid consumption with the use of perineural buprenorphine or dexamethasone in TAP blocks after unilateral inguinal hernioplasties. METHODS: This prospective, randomized, double-blinded, placebo-controlled study enrolled 93 patients scheduled for unilateral inguinal hernioplasty, followed by an ultrasound-guided TAP block. The participants were randomized into 3 groups (31 patients each). Group L received 20 ml 0.25% levobupivacaine + 1 ml normal saline (NS); group LB, 20 ml 0.25% levobupivacaine + 0.3 mg (1 ml) buprenorphine; and group LD, 20 ml 0.25% levobupivacaine + 4 mg (1 ml) dexamethasone. The patients were observed postoperatively for 24 h for first rescue analgesic requirement, total rescue analgesic consumption, and pain scores on the numeric rating scale (NRS). RESULTS: The time to first rescue analgesic requirement was significantly longer in Group LB than in groups LD and L (688.87 ± 36.11 min, 601.45 ± 39.85 min, and 383.06 ± 36.21 min, respectively; P < 0.001). The mean total tramadol consumption in the first 24 h was the lowest in group LB (P < 0.001, L vs. LB / LD). Groups LB and LD displayed significantly lower NRS scores than group L (P < 0.001 both). CONCLUSIONS: Levobupivacaine with perineural buprenorphine in a TAP block after unilateral open inguinal hernioplasty facilitates prolonged analgesia and reduced requirement for rescue analgesics compared to perineural dexamethasone, without significant side effects.
Abdominal Wall ; Analgesia ; Analgesics ; Buprenorphine ; Dexamethasone ; Hernia, Inguinal ; Herniorrhaphy ; Humans ; Prospective Studies ; Tramadol ; Ultrasonography