[Effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice].

OBJECTIVE: To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis. METHODS: A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CD3 were detected by immunohistochemistry; the expression level of serum interleukin (IL) -17A was detected by ELISA, and the relative expressions of tumor necrosis factor-α (TNF-α), IL-1ß and IL-6 mRNA in skin lesions were detected by real-time PCR. RESULTS: The increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (P<0.01). The scale score, infiltration score, and total score of PASI in the moxibustion group were lower than those in the model group (P<0.01); the infiltration score and total score of PASI in the medication group were lower than those in the model group (P<0.01, P<0.05). The inflammatory cell infiltration in the model group was obvious, and the thickness of epidermal layer was increased compared with that in the normal group (P<0.01); the inflammatory cell infiltration and Munro micro abscess were decreased in the moxibustion group and the medication group, and the thickness of epidermal layer was decreased compared with that in the model group (P<0.01). Compared with the normal group, the positive cell number of PCNA and T was increased (P<0.01), and the body mass was decreased, and the spleen index was increased (P<0.01), and the expression of serum IL-17A and the relative expression of TNF-α, IL-1ß and IL-6 mRNA in the skin lesions was increased in the model group (P<0.01). Compared with the model group, the positive cell number of PCNA and T was reduced (P<0.01), and the spleen index and the relative expression of TNF-α, IL-1ß and IL-6 mRNA were reduced (P<0.01) in the moxibustion group and the medication group; the body mass of mice in the moxibustion group was higher than that in the model group (P<0.01); the content of serum IL-17A in the medication group was lower than that in the model group (P<0.01); the relative expression of TNF-α, IL-1ß mRNA in the moxibustion group was higher than that in the medication group (P<0.01). CONCLUSION: Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway.

BACKGROUND: Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. METHODS: Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). RESULTS: Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. CONCLUSIONS: SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

Fire needle acupuncture or moxibustion for chronic plaque psoriasis: study protocol for a randomized controlled trial.

BACKGROUND: Psoriasis is a chronic, immune-mediated disorder with chronic plaque psoriasis being the primary manifestation during the remission stage. Patients often have a slow course and long history of the disease. The refractory type of psoriasis is a stubborn rash that does not subside easily. We designed this randomized controlled trial to compare the effectiveness and relapse rates of plaque psoriasis in patients treated with either acupuncture, moxibustion or calcipotriol ointment. The ultimate aim of the study is to select an effective traditional Chinese medicine therapy for patients with plaque psoriasis. METHODS: The study will be a multicenter, prospective, randomized controlled trial that compares the effectiveness of fire needle therapy, moxibustion and calcipotriol ointment. In total, 160 patients with plaque psoriasis who meet the inclusion criteria will be recruited from three hospitals in Beijing and then randomly assigned to receive either fire needle therapy (group A1), moxibustion (group A2) or calcipotriol ointment (group B). All participants will receive an 8-week treatment and will then be followed up for another 24 weeks, with time points at weeks 12 and 24 after treatment completion. The primary outcomes to be measured are relapse rates and psoriasis area and severity index score of the target lesions. In addition, the target lesion onset time, dermatology life quality index, traditional Chinese medicine syndrome score, and the relapse interval of the target lesion will be measured. Adverse events will be recorded for safety assessment. DISCUSSION: The aim of this study is to determine whether fire needle therapy or moxibustion could improve the clinical effectiveness for psoriasis lesions and reduce the relapse rate. Once completed, it will provide information regarding therapeutic evaluation on fire needle therapy or moxibustion for plaque psoriasis, which will assist clinicians in selecting the most effective treatment options for patients. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ChiCTR1800019588. Registered on 19 November 2018.

The Effect of Ginkgo Biloba Dropping Pills on Hemorheology and Blood Lipid: A Systematic Review of Randomized Trials.

OBJECTIVE: A systematic review of randomized trials was performed to assess the effect of Ginkgo Biloba Dropping Pills (GBDP) on clinical hemorheology and blood lipid indicators. METHODS: The data of the Embase, Cochrane Library, PubMed, Clinical Trials, China National Knowledge Infrastructure, the Wanfang database, the VIP database, and the Sinomed were retrieved by computers from the establishment of the database to March 27, 2018, and screened and extracted by two researchers according to inclusion and exclusion criteria. Cochrane 5.0 recommended bias risk assessment tool was used to evaluate the methodological quality of the included literature, and Revman 5.3 software were used for meta-analysis. RESULTS: 10 literatures were finally selected in accordance with the standard. There were a total of 1201 cases, 608 cases in ginkgo biloba dropping pill group and 593 in routine treatment group. Compared with control group, GBDP significantly improved plasma viscosity [N=383, RR= - 0.45, 95%CI=(-0.86,-0.04), P=0.03], whole blood high shear [N=232, RR= - 0.92,95%CI=(-1.69, -0.16), P =0.02], whole blood low shear [N = 232, RR = - 2.22, 95% CI = (- 3.74, -0.7), P = 0.004], red blood cell specific volume [N =132, RR = - 4.55, 95% CI = (- 6.36, 2.73), P < 0.000 01], fibrinogen [N=243, RR=-0.60,95%CI=(-0.82,-0.39), P<0.00001], triglyceride [N=912, RR=-0.60,95%CI=(-1.12, -0.07), P =0.03], cholesterol [N=912, RR=-0.97,95%CI=(-1.41, -0.52), P <0.0001], low-density cholesterol [N=1100, RR=-0.72,95%CI=(-1.19, -0.25), P =0.003], and sensitivity analysis before and after of high-density cholesterol [N=1020, RR=0.08,95%CI=(-0.17,0.34), P =0.52] and [N=683, RR=0.27,95%CI=(0.13,0.42), P =0.0003]. And seven adverse reactions were reported. CONCLUSION: GBDP can improve hemorheology indexes, which is to reduce the blood viscosity, to improve blood lipid status, and to prevent and treat cardiocerebral and renal vascular diseases to a certain extent, with slight clinical adverse reactions. But our results were based on small amount of clinical studies with poor quality and insufficient evidence, which may lead to low credibility of conclusions. Therefore, more large-sample, multiple-center, randomized controlled clinical trials and related mechanisms researches are needed to obtain better clinical trial evidence in order to verify the further effectiveness and safety of GBDP on hemorheology.

Paeonol inhibits the development of 1­chloro­2,4­dinitrobenzene­induced atopic dermatitis via mast and T cells in BALB/c mice.

Our previous studies suggested that paeonol, the active constituent of the traditional Chinese medicine Cortex Moutan, may be an effective treatment for inflammatory disorders. In the present study, the therapeutic potential of paeonol on atopic dermatitis (AD) was investigated using animal and cell experiments. AD­like lesions were induced by repeated application of 1­chloro­2,4­dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice, and P815 cells were used for in vitro assays. The skin lesions, serum and spleens of the mice were analyzed using lesion severity scoring, histological analysis, flow cytometry, reverse transcription­quantitative polymerase chain reaction, western blotting and ELISA, in order to investigate the anti­AD effects of paeonol. In addition, western blotting and ELISA were conducted for in vitro analysis of P815 cells. The results demonstrated that oral administration of paeonol inhibited the development of DNCB­induced AD­like lesions in the BALB/c mice by reducing severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of immunoglobulin E and inflammatory cytokines [interleukin (IL)­4, histamine, IL­13, IL­31 and thymic stromal lymphopoietin], along with regulation of the T helper (Th) cell subset (Th1/Th2) ratio. Application of paeonol also reduced the protein expression levels of phosphorylated (p)­p38 and p­extracellular signal­regulated kinase (ERK) in skin lesions. In vitro, paeonol reduced the expression levels of tumor necrosis factor­α and histamine in P815 cells, and inhibited p38/ERK/mitogen­activated protein kinase signaling. The present findings indicated that paeonol may relieve dermatitis by acting on cluster of differentiation 4+ T and mast cells; therefore, paeonol may represent a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.

Matrine alleviates imiquimod-induced psoriasiform dermatitis in BALB/c mice via dendritic cell regulation.

Matrine, is a bioactive compound isolated from Sophora flavescens (Ku shen), an herb used in Chinese traditional medicine that possesses wide-reaching pharmacological action. Psoriasis is a chronic relapsing inflammatory disorder with an incompletely understood pathophysiology, and dendritic cells (DCs) play a central role in the disease. This study aimed to explore DCs related potential mechanisms based on the effect of matrine on imiquimod (IMQ)-induced psoriasiform dermatitis in BALB/c mice and DCs simulated by resiquimod. Mice with IMQ-induced psoriasiform cutaneous lesions were treated with matrine [12.5, 25 or 50 mg/(kg·d), for 6 days]. Morphology, histological changes, keratinocyte proliferation and differentiation, inflammatory cell infiltration, protein expression levels of myeloid differentiation factor 88 (MyD88), and mRNA expression levels of inflammatory factors [interleukin (IL)-12, IL-23, and IL-1ß] in lesional skin were assessed. The application of matrine decreased the proliferation of IMQ-induced keratinocytes. The treatment attenuated the infiltration of PCNA+ and CD3+ cells in the lesions. Matrine reduced the expression of the MyD88 protein and the inflammatory factors' mRNA in lesional skin, but also in BMDCs (bone marrow derived dendritic cells). These results indicated that matrine suppressed expression of the inflammatory factors by decreasing the expression of the MyD88 protein on the surface of BMDCs, finally alleviating psoriasiform skin lesions. Therefore, the findings suggest that matrine might be a potential candidate for treating psoriasis.

Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial.

BACKGROUND: The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients. METHODS: A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events. RESULTS: Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity. CONCLUSIONS: In conjunction with prednisone, TAC may be an alternative therapeutic regimen for adult SRNS patients. However, adverse events in these patients should be carefully monitored, especially at the beginning of treatment. Randomized controlled trials with longer follow-up are warranted.