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

OBJECTIVE: To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization (MR) study. METHODS: A two-sample MR study was performed using summarized statistics from the genome-wide association studies (GWAS) conducted in reproductive traits, as well as GWAS data on overall psoriasis, psoriatic arthritis (PsA), and psoriasis vulgaris (PV). Besides univariable MR (UVMR), multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index (BMI). RESULTS: Genetically predicted early age at first sexual intercourse (AFS) led to an increased risk of overall psoriasis [odds ratio ( OR) _UVMR: 0.54]; 36.13% of this effect was mediated through BMI and 47.79% through educational attainment. The direct negative casual association between age at first birth (AFB)-PsA was dominant ( OR _UVMR: 0.76), with 49.61% proportion of the mediation due to BMI. The mediating effect was found for BMI on the AFS-PV relationship, which accounted for 26.27% of the proportion. AFS was inversely associated with the risk of overall psoriasis and PV, with considerable mediation by BMI and educational attainment. CONCLUSION Early AFB may cause a higher risk of PsA, while the AFS-PsA association was fully mediated by BMI.
Humans ; Body Mass Index ; Psoriasis/etiology* ; Mendelian Randomization Analysis ; Educational Status ; Female ; Genome-Wide Association Study ; Risk Factors ; Male ; Reproduction ; Adult

Colitis, Ulcerative ; complications ; drug therapy ; Humans ; Male ; Middle Aged ; Psoriasis ; complications ; drug therapy ; Pyoderma Gangrenosum ; drug therapy ; etiology

Psoriasis is a chronic inflammatory disease related to genome-wide and surroundings, it is important to develop a suitable animal model to research psoriasis pathogenesis and evolve pharmacotherapeutics. With the development of transgenetic technology in the past few years, psoriasis virulence gene animal model become a hotspot. Research of animal model of human psoriasis genes is reviewed in the paper.
Aminoquinolines ; toxicity ; Amphiregulin ; Animals ; Disease Models, Animal ; EGF Family of Proteins ; genetics ; metabolism ; Humans ; Keratin-14 ; genetics ; metabolism ; Keratin-5 ; genetics ; metabolism ; Keratinocytes ; metabolism ; Membrane Glycoproteins ; agonists ; Mice, Transgenic ; Psoriasis ; etiology ; genetics ; metabolism ; Receptor, TIE-2 ; genetics ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; Toll-Like Receptor 7 ; agonists ; Transforming Growth Factor beta1 ; genetics ; metabolism

Psoriasis is an immune-abnormal, chronic, proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors. It causes worldwide concern because of its high-prevalence, harmful and incurable characteristics. Over the years, Chinese medicine (CM) treatment of psoriasis has accumulated a wealth of clinical experience. Disease-syndrome combination, which achieves more satisfactory clinical effect, is the basis to highlight the special CM advantages in treating psoriasis. In this paper, we review the advantages of treating psoriasis with the combination of disease and syndrome, analyze the prospects of research on treating psoriasis combining disease with syndrome. We also make a point that there are several key points for the clinical research of combination of disease and syndrome. It can be expected that carrying out clinical research on the combination of disease and syndrome will help improve the clinical efficacy of medical treatment of psoriasis, which will be the main direction of research in the future.
Biomedical Research ; trends ; Humans ; Medicine, Chinese Traditional ; Psoriasis ; etiology ; therapy ; Syndrome ; Treatment Outcome

Dental Amalgam ; adverse effects ; therapeutic use ; Dental Caries ; therapy ; Dentists ; legislation & jurisprudence ; Dissent and Disputes ; legislation & jurisprudence ; Humans ; Impetigo ; etiology ; Liability, Legal ; Psoriasis ; etiology

OBJECTIVETo analyze and investigate the rules for drug utilization of Chinese medicine for the treatment of psoriasis vulgaris with blood-heat syndrome.

METHODSThe literatures that met the following inclusion criteria were screened out from China National Knowledge Infrastructure (CNKI) from January 1998 to December 2008, including the compositions and dosages of the recipes reported completely and accurately, the sample size being [Symbol: see text] 30 cases and the total effective rate being [Symbol: see text] 70%.

RESULTSIn total, 289 papers meeting the inclusion criteria were retrieved, involving 301 recipes; in which 111 recipes consisting of 145 individual drugs were the function for clearing the heat, accounting for 52.84%. The three drugs with the highest utilized frequency were Radix Rehmanniae, Radix Arnebiae seu Lithospermi and Cortex Moutan. Meridian adscription of the drugs was mainly the Gan-meridian.

CONCLUSIONThere were rules for the treatment of psoriasis vulgaris of blood-heat syndrome with Chinese medicine prescriptions.

Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; therapeutic use ; Hematologic Diseases ; drug therapy ; etiology ; Hot Temperature ; Humans ; Medicine, Chinese Traditional ; methods ; Psoriasis ; complications ; drug therapy ; Review Literature as Topic ; Syndrome

Cases of psoriasis complicated with venous thromboembolism are rarely reported. Here, we report two cases and review the current literature on the subject. Two patients with long-standing severe psoriasis presented with chest pain, shortness of breath and breathing difficulties. The patients were diagnosed using lung ventilation-perfusion scans or computed tomographic pulmonary angiography. Anticoagulation or thrombolytic therapy was initiated, and long-term continuous anticoagulation with warfarin prevented any recurrences.
Aged ; Humans ; Male ; Middle Aged ; Psoriasis ; complications ; Venous Thromboembolism ; etiology

BACKGROUNDPsoriasis is a common inflammatory skin disease, yet knowledge of the factors that may induce, trigger, or exacerbate psoriasis is not fully delineated. Recent advances have improved our understanding of the link between psoriasis and cell-wall-deficient bacteria (CWDB) infections. In the present study we assessed the prevalence of CWDB infection in patients with psoriasis.

METHODSThe carriage rate of CWDB in the tonsil or pharynx of psoriasis patients, chronic tonsillitis patients and controls were investigated using hypertonic medium. Psoriasis patients with CWDB were randomly assigned to two groups and respectively treated with antibiotics or systemic therapy without antibiotic. Human peripheral blood mononuclear cells (PBMC) from psoriasis patients, chronic tonsillitis patients and control subjects were stimulated with bacteria antigens and extra-cellular levels of interferon-gamma (IFN-gamma) and interleukin (IL)-10 were measured in the supernatants using the ELISA technique, in vitro. Meanwhile, the proliferation ability of PBMC to respond to bacteria antigens was detected by MTT assay.

RESULTSCWDB were isolated from 74.2% of psoriasis patients, 23.5% of chronic tonsillitis patients and only 6.3% of controls. Antibiotic therapy was appropriate for approximately 80% of psoriasis patients with CWDB infection, and in only 8.9% psoriasis patients CWDB infection was detected after antibiotic therapy. Meanwhile, our study showed that CWDB and wide-type bacteria did remarkably enhance the production of IFN-gamma, in vitro, and PBMC proliferation.

CONCLUSIONCWDB infection may be a virtual triggering factor in psoriasis by regulating T-cell activation.

Adult ; Anti-Bacterial Agents ; therapeutic use ; Bacteria ; cytology ; drug effects ; isolation & purification ; Cell Wall ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Male ; Middle Aged ; Psoriasis ; drug therapy ; etiology ; metabolism ; microbiology ; Young Adult

Psoriasis is a common, chronic, recurrent inflammatory skin disorder whose etiology is still unknown. It is believed that a multiple-gene inheritance is involved and it also involves various factors such as immunity, inflammation, cell proliferation, apoptosis, neural media, etc. Since cytokines are key mediators in inflammation, a number of Chinese medicines (CMs) have been reported to have certain antagonist effects on pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), platelet active factor (PAF) and interleukin-8 (IL-8). Some researches on CMs have made significant breakthroughs in psoriasis by intervening with cytokines. Abnormalities with keratinocyte proliferation and apoptosis are considered to be present in patients with psoriasis and a number of studies show that the mechanism of CMs on psoriasis may be through the inhibition of the keratinocyte proliferation and induction of apoptosis. Other studies also show that the inhibition of fibroblast-secreted cytokines could regulate keratinocyte proliferation and differentiation and reduce the level of Calcitonin gene-related peptide (CGRP) in plasma and in lesions so as to slow down the process of inflammation and proliferation in psoriasis. The most commonly used models for psoriasis are the scaled tails or the vaginal epithelium of mice in China. They were used to observe the histopathological changes after the model mice were treated with CMs with the inhibition on the mitosis of vaginal epithelium or promotion of granular layer in rat tail taken as the indices of clinical efficacy. A variety of signs occur in psoriasis patients with TCM blood-stasis syndrome type and the effect of CMs in activating blood circulation to remove blood stasis on psoriasis suggested that the mechanism of CMs may be partially correlated to hemorrheology and microcirculation. Along with the continuous development of the biosciences, some TCM theories for psoriasis have been confirmed by laboratory studies. However, the exploration into traditional Chinese medicines' biomechanics in psoriasis and the therapeutic mechanism of CMs by integrative medicine still requires further studies.
Animals ; China ; Cytokines ; physiology ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Fibroblasts ; drug effects ; physiology ; Hemorheology ; Humans ; Keratinocytes ; drug effects ; physiology ; Materia Medica ; administration & dosage ; Medicine, Chinese Traditional ; methods ; Microcirculation ; drug effects ; physiology ; Neuropeptides ; physiology ; Psoriasis ; etiology ; pathology ; therapy ; Research ; trends