Identification of characteristic genes and herbal compounds for the treatment of psoriasis based on machine learning and molecular dynamics simulation.

Psoriasis brings economic and mental burdens to patients, the exact etiology and pathogenesis of psoriasis are still unclear. Compounds of herbal medicine have the potential for psoriasis treatment. This study aims to explore the characteristic genes for psoriasis, which herbal compounds may target. Four differential gene expression datasets, with 181 healthy skin and 181 psoriasis skin lesion samples, were used for analysis. This study employed random forest, neural network, and support vector machine algorithms to identify the characteristic genes associated with psoriasis. The identified genes were validated using external datasets. Then, the main compounds were identified. The targets of compounds were collected through SwissTargetPrediction, Super-PRED, HERB databases, and so on. Finally, a batch virtual screening of compounds with the identified characteristic genes was conducted. Open Babel and AutoDock Tools 1.5.6 were used for molecular docking, and Desmond was used to evaluate molecular dynamics simulations. Twelve characteristic genes, successfully validated in external datasets genes, were identified from 1270 differential genes. The 59 compounds identified contained 1795 targets. There are 143 intersections between differential genes and compound targets. Two-hundred and ninety-four compound-target combinations were selected for molecular docking screening. It was finally found that 8 protein-ligand combinations are highly critical for treating psoriasis, namely AKR1B10-Astilbin, AKR1B10-Ferulic acid, AKR1B10-Cianidanol, IL36G-Astilbin, MMP9-Ferulic acid, OASL-Astilbin, PPARG-Astilbin, SERPINB3-Astilbin, molecular dynamics simulations also indicate that these eight pairs of combinations are stable. This research brings a new perspective to the treatment of psoriasis, these characteristic genes and compounds deserve the attention of clinical researchers.Communicated by Ramaswamy H. Sarma.

Chromosome-level genome of Ambrosia trifida provides insights into adaptation and the evolution of pollen allergens.

Ambrosia trifida (giant ragweed) is an invasive plant that can cause serious damage to natural ecosystems and severe respiratory allergies. However, the genomic basis of invasive adaptation and pollen allergens in Ambrosia species remain largely unknown. Here, we present a 1.66 Gb chromosome-scale reference genome for giant ragweed and identified multiple types of genome duplications, which are responsible for its rapid environmental adaptation and pollen development. The largest copies number and species-specific expansions of resistance-related gene families compared to Heliantheae alliance might contribute to resist stresses, pathogens and rapid adaptation. To extend the knowledge of evolutionary process of allergic pollen proteins, we predicted 26 and 168 potential pollen allergen candidates for giant ragweed and other Asteraceae plant species by combining machine learning and identity screening. Interestingly, we observed a specific tandemly repeated array for potential allergenic pectate lyases among Ambrosia species. Rapid evolutionary rates on putative pectate lyase allergens may imply a crucial role of nonsynonymous mutations on amino acid residues for plant biological function and allergenicity. Altogether, this study provides insight into the molecular ecological adaptation and putative pollen allergens prediction that will be helpful in promoting invasion genomic research and evolution of putative pollen allergy in giant ragweed.

[Analysis and prospects of common problems in clinical data mining of traditional Chinese medicine prescriptions].

Mining data from traditional Chinese medicine(TCM) prescriptions is one of the important methods for inheriting the experience of famous doctors and developing new drugs. However, current research work has problems such as to be optimized research plans and non-standard statistics. The main problems and corresponding solutions summarized by the research mainly include four aspects.(1)The research plan design needs to consider the efficacy and quality of individual cases.(2)The significance of the difference in confidence order of association rules needs to be further considered, and the lift should not be ignored.(3)The clustering analysis steps are complex. The selection of clustering variables should comprehensively consider factors such as the frequency of TCM, network topology parameters, and practical application significance. The selection of distance calculation and clustering methods should be improved based on the characteristics of TCM clinical data. Jaccard distance and its improvement plan should be given attention in the future. A single, unexplained clustering result should not be presented, but the final clustering plan should be selected based on a comprehensive consideration of TCM clinical characteristics and objective evaluation indicators for clustering.(4)When calculating correlation coefficients, algorithms that are only suitable for continuous variables should not be applied to binary variables. This article explained the connotations of the above problems based on the characteristics of TCM clinical research and statistical principles and proposed corresponding suggestions to provide important references for future data mining research work.

Inhibition of invasive plant Mikania micrantha rapid growth by host-specific rust (Puccinia spegazzinii).

Mikania micrantha Kunth is a fast-growing global invasive weed species that causes severe damage to natural ecosystems and very large economic losses of forest and crop production. Although Puccinia spegazzinii can effectively inhibit the growth of M. micrantha and is used as a biological control strain in many countries, the mechanism of inhibiting the growth of M. micrantha is not clear. Here, we used a combination of phenotypic, enzyme activity, transcriptomic, and metabolomic approaches to study the response of M. micrantha after infection by P. spegazzinii. In the early stages of rust infection, jasmonic acid (JA), jasmonoyl-isoleucine (JA-Ile), and salicylic acid (SA) levels in infected leaves were significantly lower than those in uninfected leaves. In teliospore initial and developed stages of P. spegazzinii, JA and JA-Ile levels substantially increased by more than 6 times, which resulted in a significant decrease in the accumulation of defense hormone SA in infected leaves of M. micrantha. The contents of plant growth-promoting hormones were significantly reduced in the infected plants as a result of substantial downregulation of the expression of key genes related to hormone biosynthesis. Furthermore, rust infection led to high levels of reactive oxygen species in chloroplasts and the destruction of chlorophyll structure, which also led to decreased photosynthetic gene expression, net photosynthetic rate, activity of Rubisco, and levels of important organic acids in the Calvin cycle. We hypothesized that after P. spegazzinii infection, JA or JA-Ile accumulation not only inhibited SA levels to promote rust infection and development, but also impeded the rapid growth of M. micrantha by affecting plant growth hormones, carbon, and nitrogen metabolic pathways.

Panax Notoginseng Saponins Regulate Transforming Growth Factor-ß1 through MAPK and Snail/TWIST1 Signaling Pathway to Inhibit Epithelial-Mesenchymal Transition of Pulmonary Fibrosis in A549 Cells.

Panaxnotoginseng saponins (PNS) is one of the active components of traditional Chinese medicine Panax notoginseng which has the function of reducing oxygen consumption, expansion of the cerebrovascular system, and is antithrombotic. PNS also plays a role in the treatment of pulmonary fibrosis. In this study, we found that PNS suppresses fibroblast-like changes in A549 cells through epithelial-mesenchymal transition (EMT). PNS promoted E-cadherin (E-cad) in epithelial cells and decreased Fibronectin (FN) and Vimentin (Vim) expression in myofibroblasts in a dose-dependent manner. Further mechanism studies have shown that PNS inhibits the EMT process by regulating p38, JNK, and Erk signaling factors in the MAPK signaling pathway and then blocking Snail and TWIST1 transcription factors from entering the nucleus. This indicates that PNS can regulate epithelial-mesenchymal transition through MAPK and the Snail/TWIST1 signaling pathway, thereby exerting its antipulmonary fibrosis effect.

Preventive online and offline health management intervention in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a cause of infertility. Hypothalamus-pituitary-ovarian axis dysregulation is important in the pathogenesis of PCOS and the associated chronic excess of sex hormones can lead to cardiovascular and cerebrovascular diseases, diabetes, and malignancies such as endometrial cancer, and breast cancer. At present, most scholars agree that lifestyle interventions in conjunction with drug treatment can help PCOS patients achieve their goals of successful pregnancy and childbirth. AIM: To investigate the clinical effect of an online and offline (O2O) preventive health management model on PCOS with kidney deficiency and phlegm dampness. METHODS: A total of 82 patients with PCOS of the kidney deficiency and phlegm dampness type who were admitted to Beijing Luhe Hospital Affiliated to Capital Medical University from April 2019 to June 2020 were randomly divided into two groups. The treatment group was treated with oral Diane-35 for 3 mo and received preventive O2O medical health management for 6 mo (including eating and living, exercise, drug management). The control group was treated with oral Diane-35 for 3 mo and completed outpatient health education. The traditional Chinese medicine (TCM) syndrome score, acne score, hair score, sex hormone level and clinical effects were compared between the two groups before and after the intervention. RESULTS: After treatment, the TCM syndrome score, acne score, and serum luteinizing hormone/follicle stimulating hormone level were significantly lower in the treatment group than in the control group (P < 0.05). After 3 mo of treatment, the TCM syndrome curative effect index in the treatment group was 97.30% compared to 54.05% in the control group (P < 0.05), whereas the total treatment effect in the treatment group was 91.89%, compared to 54.05% in the control group (P < 0.05). CONCLUSION: An integrated therapeutic approach incorporating medication, TCM methods and social media is more effective than standard treatment for PCOS.

[Moxibustion on plaque psoriasis of blood stasis: a randomized controlled trial].

OBJECTIVE: To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment. METHODS: A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to ashi point (target skin lesions), Zusanli (ST 36), Xuehai (SP 10) and Qihai (CV 6) for 30 min each time, 3 times a week. The control group was treated with calcipotriol ointment (0.25 g each time, once in the morning and evening) on the target skin lesions. Both groups were treated for 8 weeks. The psoriasis area and severity index (PASI) score before and after treatment, main clinical symptoms of TCM score and dermatology life quality index (DLQI) score before and after treatment and 3 and 6 moths follow-up were observed in the two groups; the clinical efficacy after treatment was evaluated and the recurrence rates of the two groups were followed up for 3 and 6 months after treatment. RESULTS: After treatment, the PASI scores in the both groups were lower than before treatment (P<0.01). After treatment and 3 and 6 months follow-up, the main clinical symptoms of TCM scores and DLQI scores of the two groups were lower than those before treatment (P<0.05), and at 3 and 6 months follow-up, those in the observation group were lower than the control group (P<0.01). There was no statistically significant difference between the observation group and the control group in overall effective rate and target skin lesion effective rate (P>0.05). At 3 and 6 months follow-up, the overall recurrence rate and target skin lesion recurrence rate in the observation group were lower than those in the control group (P<0.05). CONCLUSION: Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Yangxue Jiedu Fang Ameliorates Psoriasis by Regulating Vascular Regression via Survivin/PI3K/Akt Pathway.

BACKGROUND: Psoriasis (PA) is a chronic autoimmune disease of the skin that adversely affects patients' quality of life. Yangxue Jiedu Fang (YXJD) has been used for decades to treat psoriasis in China. However, its antipsoriatic mechanisms are still poorly understood. In this study, we explored the effects of YXJD on angiogenesis and apoptosis of microvessels in PA, the underlying mechanisms in HUVEC cells transfected by Survivin overexpression plasmid and in a mouse model of imiquimod-induced psoriasis and the relationship between VEGF (vascular endothelial growth factor) and Survivin. METHODS: A BALB/c mouse model of imiquimod- (IMQ-) induced PA was established, and the mice were treated with YXJD. Cell viability was assessed by CCK8 assay. Apoptosis was detected by annexin V-FITC/PI double-staining and caspase-3 assays. The PI3K/Akt/ß-catenin pathway was analyzed by western blotting, ELISA, and immunochemical analysis. RESULTS: YXJD ameliorated symptoms and psoriasis area and severity index (PASI) scores and also reduced the number of microvessels, as determined by the microvessel density (MVD). The expression of apoptotic protein Survivin in endothelial cells, autophagy-related proteins p62, and angiogenic proteins VEGF was inhibited by YXJD, and the repressed expression of LC3II/I increased by YXJD. The proteins related to the PI3K/Akt pathway and ß-catenin expression and the nuclear entry of ß-catenin were reduced in IMQ-induced PA mice treated with YXJD. In HUVEC cells transfected by Survivin overexpression plasmid, we observed YXJD regulated the expression of Survivin, LC3II/I, and p62, VEGF, and PI3K/Akt pathway-relative proteins and the nuclear entry of ß-catenin. CONCLUSIONS: YXJD inhibited the expression of Survivin via PI3K/Akt pathway to adjust apoptosis, autophagy, and angiogenesis of microvessels and thus improve the vascular sustainability in psoriasis. YXJD may represent a new direction of drug research and development for immunomodulatory therapy for psoriasis.

Acupuncture combined with herbal medicine versus herbal medicine alone for plaque psoriasis: a systematic review protocol.

BACKGROUND: Psoriasis is a condition with a multifactorial etiopathogenesis worldwide, and plaque psoriasis, which is characterized by redness, thickness, and scaling, is the most common kind. Individuals living with psoriasis show low levels of life quality, and having fewer or less extensive lesions may improve spiritual and mental health. Therefore, our objective is to explore the effectiveness of acupuncture combined with herbal medicine for plaque psoriasis and to compare acupuncture combined with herbal medicine with herbal medicine alone. METHODS: Databases including PubMed, MEDLINE, the Cochrane Library, Excerpta Medica (EMBASE), the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure Database (CNKI), the Wanfang database and the Chinese Scientific Journal Database (VIP database) will be searched from inception to March 2018. We will employ hand searches, and grey literature will also be obtained. Only randomized controlled trials evaluating acupuncture combined with herbal medicine to treat plaque psoriasis in adults will be assessed. The Psoriasis Area and Severity Index score (PASI score), the itching index, the life quality scores, and the anxiety index will be the outcome measures. Two independent reviewers will select the articles included, assess the risk of bias and extract data according to the inclusion criteria. A third reviewer will resolve disagreements. The purpose of this study will be to identify the effect of acupuncture combined with herbal medicine on the lesions (PASI score), symptoms (itching index, life quality scores) and mental status (anxiety index) of the patients. DISCUSSION: The meta-analysis will retrospectively examine current evidence regarding the effectiveness of the practice of acupuncture combined with herbal medicine to treat plaque psoriasis. This study may reveal, for the first time, an adjuvant therapy for psoriasis. TRIAL REGISTRATION: As the study is a systematic review protocol, trial registration will not be necessary. An article containing the results will be published in a peer-reviewed journal and disseminated through scientific conferences.

Effect of Traditional Chinese Medicine plus narrow-band medium-wave ultraviolet B radiation on moderate-to-severe psoriasis vulgaris in a case series.

OBJECTIVE: To investigate the efficacy and safety of Traditional Chinese Medicine (TCM) therapy combined with ultraviolet B light therapy in the treatment of moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe psoriasis (skin lesion area > 10% of the body surface area) for 2 consecutive years were treated with TCM (oral and external use of herbal medicines, acupuncture, and herbal bathing) and narrow-band medium-wave ultraviolet B light treatment for 12 weeks. The treatment effect was evaluated based on the Psoriasis Area Severity Index (PASI), the achievement of a 50% reduction in the PASI (PASI50), the achievement of a 75% reduction in the PASI (PASI75), pruritus score, Dermatology Life Quality Index, and safety. RESULTS: A total of 95 outpatients were enrolled, and 92 subjects (96.8%) completed the 12-week treatment course. At baseline, the average proportion of the body surface area covered by skin lesions was 12.4%, and the average PASI was 17.7. All patients had previously been treated with conventional medicine (89.1% of patients received ultraviolet light treatment, 50.0% received glucocorticoids, and 21.7% received acitretin). After the 12-week treatment course, 22 patients (23.9%) achieved PASI75, and 43 (46.7%) achieved PASI50. The post-treatment pruritus score and Dermatology Life Quality Index of all treated patients were significantly lower than the respective baseline values (P < 0.0001). No adverse effects were detected by the monitoring of blood, urine, stools, liver and kidney function, and echocardiography. CONCLUSION: Comprehensive therapy comprising TCM therapy combined with ultraviolet B light therapy achieved good outcomes for patients with moderate-to-severe psoriasis.

Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome: a multi-center, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Traditional Chinese medicine (TCM) has a long history in the treatment of psoriasis vulgaris. We aimed to evaluate the clinical efficacy and safety of Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Participants with psoriasis vulgaris of blood-heat syndrome were blinded and randomized to receive Pulian ointment or placebo ointment twice daily for 4 weeks, with follow-up 8 weeks after treatment. Psoriasis Area Severity Index (PASI) scores, severity of each symptom and area of skin lesion and quality of life were assessed at baseline, 2 weeks, and 4 weeks. Adverse events were recorded during the study. SAS 9.4 software and SPSS 17.0 software was applied for data analysis. RESULTS: A total of 300 participants with psoriasis vulgaris of blood-heat syndrome were assessed for eligibility, and 294 were randomly assigned to the Pulian ointment and placebo group from six study centers. Full analysis set (FAS): after 4 weeks of treatment, there were significant differences between groups in PASI score and the separate score of skin lesion area, favoring Pulian ointment group (P < 0.05). However, no significant differences were observed in scores of scaling, erythema and induration/thickness (P > 0.05). Per protocol set (PPS): There was no statistically significant difference in PASI score and separate score of each symptom and area of skin lesion between two groups (P > 0.05). Quality of life measured by Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health Survey (SF-36) improved after treatment in both groups, but there was no significant difference between the two groups (P > 0.05). After being followed up for 8 weeks, the total relapse rates of the Pulian Ointment group and placebo group were 5.88 and 8.45%, respectively, and the difference was not statistically significant between the two groups (P > 0.05). No adverse event was observed in both groups throughout the study. CONCLUSIONS: Pulian Ointment seems effective and well tolerated in improving the PASI score and separate score of skin lesion area for patients with psoriasis vulgaris of blood-heat syndrome. Further research could build on the current study to explore whether other preparation forms and greater intervention intensity are necessary for better therapeutic effects. TRIAL REGISTRATION: Chictr.org.cn Identifier ChiCTR-TRC-12002054 .

Multi-glycoside of Tripterygium wilfordii Hook. f. ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses.

Multi-glycoside of Tripterygium wilfordii Hook. f.(GTW) possesses anti-inflammatory and immunosuppressive properties, and has been used as a traditional treatment for psoriasis for many years, although the underlying immunological mechanisms remain poorly understood. The T helper (Th)17 cell response is considered to play a major role in the pathogenesis of psoriasis. Th17 cells are implicated in the mechanism of pathogenesis of imiquimod (IMQ)­induced skin inflammation. Using a mouse model, we demonstrated that GTW protected mice from developing psoriasis-like lesions induced by topical IMQ administration. This protection was associated with significantly decreased mRNA levels of Th17 cytokines such as interleukin (IL)-17A, IL-17F and IL-22 in mouse skin samples as well as fewer IL-17-secreting splenic CD4+ lymphocytes in IMQ-exposed mice. There were no significant effects on the proportion of CD4+ interferon (IFN)-γ+ T cells, CD4+IL-4+ T cells and CD4+CD25+Foxp3+ Treg cells in the spleen cells. Taken together with the unchanged mRNA levels of Th1 cytokine IFN-γ, Th2 cytokine IL-4 and Treg cytokine IL-10 in IMQ-exposed mouse skin following GTW administration, our findings suggest that the immunosuppressive effect of GTW in psoriasis is exerted mainly on Th17 cells, rather than on Th1, Th2 or Treg cells. Furthermore, we showed that GTW suppressed Th17 function through the inhibition of STAT3 phosphorylation. These results have the potential to pave the way for the use of GTW as an agent for the treatment of psoriasis.

Distribution and development of the TCM syndromes in psoriasis vulgaris.

OBJECTIVE: To study the distribution and development rules of the TCM syndromes in psoriasis vulgaris. METHODS: Based on the clinical epidemiologic mass survey, the study was carried out by means of a status survey, multi-center and large-sample research. The data base was set up by EPIINFO6.0. The SPSS was used to do the statistical analyses in 2651 cases of psoriasis vulgaris to study the correlations among the distribution and development of the TCM syndromes, the stages of the disease, nationality, psoriasis history, family history, smoking history, alcohol drinking history, and severity of the disease. RESULTS: The TCM syndromes in psoriasis vulgaris mainly include the blood-heat syndrome (53.8%), blood-dryness syndrome (27.4%), and blood-stasis syndrome (18.1%). Other syndromes were rarely seen, covering 0.6%. The concurrent syndromes mainly involve dampness, heat, blood stasis and toxin. The distribution differences of the main syndromes at different stages of the disease had statistical significance (P < 0.01). The syndrome distribution is not related with nationality and family history (P > 0.05), but it was closely related with the psoriasis history, smoking history, alcohol drinking history, and severity of the disease (P < 0.01). CONCLUSION: At the initial stage, psoriasis vulgaris usually manifests itself as the blood-heat syndrome, and later it may be improved or turn into the blood-dryness or blood-stasis syndrome. Smoking, alcohol consumption, and severity of the disease may play a role in the syndrome's transformation.