Expression and prognostic role of sphingosine 1-phosphate receptor 4 (S1PR4) as a biomarker of skin cutaneous melanoma.

Background: Skin cutaneous melanoma (SKCM) is one of the most lethal skin malignancies worldwide. Sphingosine 1-phosphate (S1P) regulates tumor cells through S1P receptors (S1PRs). Unlike S1PR1/2/3/5, whose anti-apoptotic effects have been widely studied, the regulatory effect of S1PR4 on tumors has not been studied extensively. In this study, we aimed to investigate the correlation between S1PR4 expression and survival, clinical manifestations, tumor microenvironment, and immune infiltration in patients with SKCM. Results: Low S1PR4 expression was associated with poor prognosis in patients with SKCM. Patients in the high-expression group had significantly longer disease survival and progression-free survival than those in the low-expression group. Conclusion: High S1PR4 expression was highly associated with better prognosis and milder clinical manifestations; thus, S1PR4 may be used as a prognostic marker to help physicians monitor patients with SKCM.

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.

Xiaoyin Jiedu Granules may alleviate psoriasis-like skin diseases in mice by regulating sphingosine 1-phosphate receptor expression and reducing Th17 cells.

Sphingosine-1-phosphate (S1P) is associated with the onset and severity of psoriasis, a chronic inflammatory skin disease linked to innate and adaptive immune responses. This study explores the therapeutic effect of Xiaoyin Jiedu Granules, a combination of traditional Chinese medicines, on psoriasis-like skin lesions in mice and the underlying mechanism. We used imiquimod (IMQ) to induce psoriasis-like dermatitis in mice; the effects of Xiaoyin Jiedu Granules on S1P receptors (S1PRs) were investigated using histology and immunohistochemistry. The effects of Xiaoyin Jiedu Granules on the proliferation, differentiation, and activation of the NF-κB pathway in keratinocytes were verified using quantitative polymerase chain reaction (qPCR) and western blotting analyses. CD4+Th17 cells were screened using flow cytometry; the effects of Xiaoyin Jiedu Granules on the differentiation of Th17 cells and the content of related inflammatory factors were also verified. S1PR1-5 was highly expressed in psoriatic lesions. Xiaoyin Jiedu Granules significantly inhibited the secretion of proliferation-related proteins (K6, K16, K17, and IL-36γ) and proinflammatory cytokines (IL-17 and IL-22), transformation of Th17 cells, and activation of the NF-κB pathway and effectively alleviated IMQ-induced psoriasis-like dermatitis. Overall, our findings indicate that Xiaoyin Jiedu Granules have anti-inflammatory activity against S1PR expression, keratinocytes, and immune cells and can therefore mitigate psoriasis. Inhibiting the expression of S1PRs may be an effective treatment strategy against psoriasis.

Knowledge Mapping of Drug Repositioning's Theme and Development.

Background: In recent years, the emergence of new diseases and resistance to known diseases have led to increasing demand for new drugs. By means of bibliometric analysis, this paper studied the relevant articles on drug repositioning in recent years and analyzed the current research foci and trends. Methodology: The Web of Science database was searched to collect all relevant literature on drug repositioning from 2001 to 2022. These data were imported into CiteSpace and bibliometric online analysis platforms for bibliometric analysis. The processed data and visualized images predict the development trends in the research field. Results: The quality and quantity of articles published after 2011 have improved significantly, with 45 of them cited more than 100 times. Articles posted by journals from different countries have high citation values. Authors from other institutions have also collaborated to analyze drug rediscovery. Keywords found in the literature include molecular docking (N=223), virtual screening (N=170), drug discovery (N=126), machine learning (N=125), and drug-target interaction (N=68); these words represent the core content of drug repositioning. Conclusion: The key focus of drug research and development is related to the discovery of new indications for drugs. Researchers are starting to retarget drugs after analyzing online databases and clinical trials. More and more drugs are being targeted at other diseases to treat more patients, based on saving money and time. It is worth noting that researchers need more financial and technical support to complete drug development.

Metabolomics and Transcriptomics Reveal the Response Mechanisms of Mikania micrantha to Puccinia spegazzinii Infection.

Mikania micrantha is one of the worst invasive species globally and can cause significant negative impacts on agricultural and forestry economics, particularly in Asia and the Pacific region. The rust Puccinia spegazzinii has been used successfully as a biological control agent in several countries to help manage M. micrantha. However, the response mechanisms of M. micrantha to P. spegazzinii infection have never been studied. To investigate the response of M. micrantha to infection by P. spegazzinii, an integrated analysis of metabolomics and transcriptomics was performed. The levels of 74 metabolites, including organic acids, amino acids, and secondary metabolites in M. micrantha infected with P. spegazzinii, were significantly different compared to those in plants that were not infected. After P. spegazzinii infection, the expression of the TCA cycle gene was significantly induced to participate in energy biosynthesis and produce more ATP. The content of most amino acids, such as L-isoleucine, L-tryptophan and L-citrulline, increased. In addition, phytoalexins, such as maackiain, nobiletin, vasicin, arachidonic acid, and JA-Ile, accumulated in M. micrantha. A total of 4978 differentially expressed genes were identified in M. micrantha infected by P. spegazzinii. Many key genes of M. micrantha in the PTI (pattern-triggered immunity) and ETI (effector-triggered immunity) pathways showed significantly higher expression under P. spegazzinii infection. Through these reactions, M. micrantha is able to resist the infection of P. spegazzinii and maintain its growth. These results are helpful for us to understand the changes in metabolites and gene expression in M. micrantha after being infected by P. spegazzinii. Our results can provide a theoretical basis for weakening the defense response of M. micrantha to P. spegazzinii, and for P. spegazzinii as a long-term biological control agent of M. micrantha.

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.

Abnormal functional connectivity in psoriasis patients with depression is associated with their clinical symptoms.

Psoriasis is a chronic, autoimmune disorder that is related to mental health disorders such as depression. However, few studies have focused on the features of brain activity in psoriasis patients with depression (PPD) and the association between brain activity and disease severity. A total of 29 PPD and 24 healthy controls were involved in this study, and all participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning. The psoriasis area and severity index (PASI) and the self-rating depression scale (SDS) were used to measure clinical symptoms. Compared with HCs, PPD patients showed increased fractional amplitude of low-frequency fluctuation (fALFF) in the Frontal_Mid_L and increased functional connectivity (FC) between the hypothalamus-R and the Cingulum_Mid_R. Correlation analysis suggested a positive correlation between PASI and SDS scores in PPD, while the fALFF and FC values were negatively correlated with their SDS and PASI scores. These brain regions may be associated with the development of depressive symptoms and disease severity in psoriasis patients.

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.

Comparison of gut microbiota compositions and corresponding genetic and metabolic features between guttate and plaque psoriasis by metagenomic sequencing.

BACKGROUND: Guttate psoriasis (GP) and psoriasis plaques (PP) are common subtypes of psoriasis. Previous studies have fully researched the association between psoriasis and gut microbiota. However, the differences in gut microbiota between GPs and PPs are still unknown. METHODS: Fecal samples were collected from 30 psoriatic patients (15 GP and 15 PP) and 15 healthy subjects. Metagenomic sequencing was then used to compare gut microbiota compositions and corresponding genetic and metabolic features between GP and PP. RESULTS: We found that the genus Megamonas was increased in PP and reduced in GP. The genus Eubacterium was increased in GP and decreased in PP. Ten KEGG pathway were significantly enriched in GP: bacterial secretion system, ribosome, sphingolipid signaling pathway, steroid hormone biosynthesis, complement and coagulation cascades, proteoglycans in cancer, FOXO signaling pathway, cGMP-PKG signaling pathway, insulin resistance, and Epstein-Barr virus infection. Ten metabolites were significantly differentially abundant between GP and PP. Among them, thiamine, biotin, butylamine, phenylethylamine, folic acid, 1,2-propanediol, and 4-aminobutyrate were enriched in PP and l-glutamate, l-glutamine, and propanoate were enriched in GP. CONCLUSIONS: These results provide a theoretical basis for the microbiome-guided stratification of patients with psoriasis.

[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.

Deciphering Gut Microbiota Dysbiosis and Corresponding Genetic and Metabolic Dysregulation in Psoriasis Patients Using Metagenomics Sequencing.

Background: Increasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking. Objectives: To comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis. Methods: DNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis. Results: Compared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes, Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides, Bifidobacterium, Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes, and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis. Conclusions: A clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches.

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.

Dysregulation of the gut-brain-skin axis and key overlapping inflammatory and immune mechanisms of psoriasis and depression.

The occurrence, progression and recurrence of psoriasis are thought to be related to mood and psychological disorders such as depression. Psoriasis can lead to depression, and depression, in turn, exacerbates psoriasis. No specific mechanism can explain the association between psoriasis and depression. The gut-brain-skin axis has been used to explain correlations among the gut microbiota, emotional states and systemic and skin inflammation, and this axis may be associated with overlapping mechanisms between psoriasis and depression. Therefore, in the context of the gut-brain-skin axis, we systematically summarized and comparatively analysed the inflammatory and immune mechanisms of psoriasis and depression and illustrated the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the gut microbiota. This review provides a theoretical basis and new targets for the treatment of psoriasis and depression.

A study on the pathogenesis of blood-heat psoriasis with transcriptome analysis.

BACKGROUND: Most existing studies on psoriasis' pathogenesis have focused on collecting epithelial cell gene sequences from psoriasis patients and normal subjects. In this paper, for the first time, high-throughput microarray was used to study the differential expression of genes in venous blood between patients with blood-heat psoriasis and normal subjects, providing theoretical support for studying the pathogenesis of blood-heat psoriasis. METHODS: Peripheral venous blood was collected from ten patients with blood-heat psoriasis and ten healthy volunteers for high-throughput microarray. The mRNAs, lncRNAs, and circRNAs related to blood-heat psoriasis were selected by analyzing the transcriptome microarray results. Then gene ontology (GO) analysis and KEGG signaling pathway analysis were used to explore further the biological functions of these mRNAs, lncRNAs, and circRNAs in blood-heat pathogenesis psoriasis. Network pharmacology was used to analyze the protein-protein interaction (PPI) network of the genes with differential expression, and the core genes to transmit information were obtained. RESULTS: A total of 205 circRNAs, 393 lncRNAs, and 157 mRNAs with differential expression associated with psoriasis were selected using high-throughput microarray. GO analysis showed these mRNAs, lncRNAs, and circRNAs were mainly enriched in cellular processes, biological regulation, ribosome formation, and negative regulation of protein binding. However, KEGG enrichment analysis suggested they were mainly enriched in autoimmunity pathways, lipid metabolism, translation, and signal transduction. PPI network analysis of mRNAs with significant difference revealed 11 core genes that transmitted information in psoriasis primarily. CONCLUSIONS: The mRNAs, lncRNAs, and circRNAs with differential expression related to the pathogenesis of blood-heat psoriasis were found using high-throughput microarray for the first time. And the mRNAs, lncRNAs, and circRNAs with potential regulatory functions related to blood-heat psoriasis were then screened by bioinformatics analysis, effectively providing a new research entry point to the pathogenesis of blood-heat psoriasis.

Plasma MicroRNA Expression Profiles in Psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis. METHODS: A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples. RESULTS: We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis. CONCLUSIONS: This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.

Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD). It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our previous research established that taVNS significantly increases amygdala-dorsolateral prefrontal cortex connectivity, which is associated with a reduction in depression severity. However, the relationship between taVNS and the central/peripheral functional state of the immune system, as well as changes in brain neural circuits, have not as yet been elucidated. In the present paper, we outline the anatomic foundation of taVNS and emphasize that it significantly modulates the activity and connectivity of a wide range of neural networks, including the default mode network, executive network, and networks involved in emotional and reward circuits. In addition, we present the inflammatory mechanism of MDD and describe how taVNS inhibits central and peripheral inflammation, which is possibly related to the effectiveness of taVNS in reducing depression severity. Our review suggests a link between the suppression of inflammation and changes in brain regions/circuits post taVNS.

Role of inflammation in depression relapse.

Major depressive disorder (MDD) is a leading cause of disability worldwide. After the first episode, patients with remitted MDD have a 60% chance of experiencing a second episode. Consideration of therapy continuation should be viewed in terms of the balance between the adverse effects of medication and the need to prevent a possible relapse. Relapse during the early stages of MDD could be prevented more efficiently by conducting individual risk assessments and providing justification for continuing therapy. Our previous work established the neuroimaging markers of relapse by comparing patients with recurrent major depressive disorder (rMDD) in depressive and remitted states. However, it is not known which of these markers are trait markers that present before initial relapse and, consequently, predict disease course. Here, we first describe how inflammation can be translated to subtype-specific clinical features and suggest how this could be used to facilitate clinical diagnosis and treatment. Next, we address the central and peripheral functional state of the immune system in patients with MDD. In addition, we emphasize the important link between the number of depressive episodes and rMDD and use neuroimaging to propose a model for the latter. Last, we address how inflammation can affect brain circuits, providing a possible mechanism for rMDD. Our review suggests a link between inflammatory processes and brain region/circuits in rMDD.