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Hyperplasia of epidermal keratinocytes that depend on glycolysis is a new hallmark of psoriasis pathogenesis. Our previous studies demonstrated that PSORI-CM02 could halt the pathological progression of psoriasis by targeting inflammatory response and angiogenesis, but its effect(s) and mechanism(s) on proliferating keratinocytes remained unclear. In this study, we aim to identify components of PSORI-CM02 that are absorbed into the blood and to determine the effect(s) of PSORI-CM02 on keratinocyte proliferation and its molecular mechanism(s). We used the immortalized human epidermal keratinocyte cell line, HaCaT, as an in vitro model of proliferating keratinocytes and the imiquimod-induced psoriasis mouse (IMQ) as an in vivo model. Metabolite profiles of vehicle pharmaceutic serum (VPS), PSORI-CM02 pharmaceutic serum (PPS), and water extraction (PWE) were compared, and 23 components of PSORI-CM02 were identified that were absorbed into the blood of mice. Both PPS and PWE inhibited the proliferation of HaCaT cells and consequently reduced the expression of the proliferation marker ki67. Additionally, PPS and PWE reduced phosphorylation levels of mTOR pathway kinases. Seahorse experiments demonstrated that PPS significantly inhibited glycolysis, glycolytic capacity, and mitochondrial respiration, thus reducing ATP production in HaCaT cells. Upon treatments of PPS or PWE, hexokinase 2 (HK2) expression was significantly decreased, as observed from the set of glycolytic genes we screened. Finally, in the IMQ model, we observed that treatment with PSORI-CM02 or BPTES, an inhibitor of mTOR signaling, reduced hyperproliferation of epidermal keratinocytes, inhibited the expression of p-S6 and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells in lesioned skin. Taken together, we demonstrate that PSORI-CM02 has an anti-proliferative effect on psoriatic keratinocytes, at least in part, by inhibiting the mTOR/HK2/glycolysis axis.

An increasing number of people are affected by overweight or obesity, and the personal and social health burden is growing rapidly. Acupuncture is gaining popularity as an alternative treatment to manage weight. This research aims to update and synthesize the evidence of acupuncture therapies from systematic reviews for treating overweight and obesity.Nine databases were searched from their inception to March 2022. Overweight or obesity was classified using standard diagnostic criteria. Published systematic reviews that included randomized controlled trials and quasi-randomized studies were eligible. Quality was assessed via the AMSTAR-2 scale and risk of bias using the ROBIS tool.Thirty-eight systematic reviews were identified. Acupuncture therapies and auricular acupoint stimulation showed benefits in terms of reducing body weight and body mass index. Catgut embedding therapy and abdominal acupuncture are currently not in widespread use with insufficient evidence. Acupuncture therapies appear to be safe. Most of the reviews were assessed as having high risk of bias and low confidence in the findings.There is a need for larger and more methodologically sound randomized controlled trials to evaluate the effectiveness of acupuncture therapies for individuals who are affected by overweight or obesity.

This review article serves to assess the consistency of recommendations from guidelines on biologic agents for psoriasis, based on the quality evaluation of psoriasis Clinical Practice Guidelines (CPGs).We conducted a systematic literature search to identify CPGs that provide recommendations on diagnosis and treatment for psoriasis. Four reviewers performed a quality assessment of the included CPGs with the Appraisal of Guidelines Research and Evaluation II (AGREE II) Instrument.A total of 51 sets of CPGs from 22 medical societies or separate working groups fulfilled the inclusion criteria. The overall quality of the eligible sets of guidelines was moderate to high, with an overall average score of 55%. The highest domain scores were Score and Purpose (70%) and Clarity of Presentation (68%). A total of 95 biologic agent recommendations were extracted from the 18 recommended CPGs. Three biologic agents (Etanercept, Adalimumab, Ustekinumab) were recommended for pediatric patients. Three biologic agents (Adalimumab, Ustekinumab, Secukinumab) were recommended as first-line biologic agents for adults with psoriasis.The overall methodological quality of CPGs for psoriasis is medium to high. More attention should be paid to applicability in guideline development. The recommendations and the basis for them among various sets guidelines were almost consistent.

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis.Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.

Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment. Activation of autophagy can be observed during myocardial injury, during which inflammatory responses are strongly triggered. Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria. In addition, autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue. In this paper, we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions, including myocardial ischemia, ischemia/reperfusion injury and sepsis cardiomyopathy.

Psoriasis is an immune-mediated, persistent inflammatory disease with a genetic predisposition, and the involvement of multiple organs in psoriasis remains indicative of systemic disease. Atherosclerosis (AS) is a common complication of patients with severe or prolonged psoriasis. The specific pathogenesis of psoriasis is still unclear. Current studies suggest that psoriasis is a polygenic genetic disease with the interaction of multiple factors such as heredity and environment. Keratinocytes are proliferated through immune-mediated inflammatory pathway, which leads to cell activation, infiltration of dermis cells and release of inflammatory factors. Activation of inflammatory cells and pro-inflammatory factors play an important role in the progression of psoriasis and atherosclerosis. Studies have found that there is a close relationship between psoriasis and atherosclerosis, and systemic inflammation may be the common feature of psoriasis and AS. This paper attempts to explore the possibility of the relationship between psoriasis and atherosclerotic comorbidities from the aspects of potential epidemiology and immune mechanism, in order to provide some reference for the subsequent scientific research.

Objective: Given the existing evidence for the analgesic effect of acupuncture, the current study aimed to assess whether acupuncture could be feasible and manageable as an adjunctive therapy for cancer pain in a real-world hospital setting. Methods: Thirty patients in an Oncology department with moderate or severe pain were recruited and randomized to an adjunctive acupuncture group or control group, who received pharmacotherapy for pain management without acupuncture. The duration of the treatment course was 1 week with a 2-week follow-up. In total, four acupuncture sessions were administered, on days 1/2/4/6 of the trial. Pain intensity was measured using a numerical rating scale (NRS) and the daily opioid dose was recorded. Results: The overall trends favored acupuncture for both pain intensity and daily opioid consumption. The proportion of participants experiencing at least a 2-point reduction in the NRS at the end of the treatment was 93% (n = 14/15) for the acupuncture group and 57% (n = 8/14) for the control group (risk difference (RD) 36.1%, 95% confidence interval (CI) [7.4%–65.0%]; relative risk (RR) 1.63, 95% CI [1.02–2.62]; p = 0.04). There were no serious adverse events and no dropouts during the treatment. Conclusion: This pilot study showed that adding acupuncture to routine analgesia for patients with cancer pain was feasible and acceptable to patients. The clinical effects of adding acupuncture as an adjunctive therapy need to be further evaluated. Clinical trial registration number: ChiCTR1800017023 (Chinese Clinical Trial Registry)

Background Psoriasis is a chronic autoimmune disease with a long disease course and frequent relapse characteristics, however, its pathogenesis is still not completely clear. Clinical study indicated that blood state is abnormal in psoriasis and seems related with the severity of psoriasis. However, whether this is true and which constituents of blood play the key role and its mechanism behind is not clear. Methods Effect of blood constituents on the psoriasis development was determined by comparing serum, red cells, and leukocytes of psoriasis on the onset of psoriasis of NOG mice, using samples of healthy people as the control. The effect of red cell on psoriasis was further demonstrated by splenectomy using Kunming mice. Red cell morphology and spleen histopathology were studied by microscope. IL-6, IL-17A, IL-23, VEGF, IL-22, MDA, NO and HIF were determined by Elisa kits, and q-PCR was used to detect the mRNA of IL-6, IL-22, and IL-23, and western blot was used to detect CD-11b, SPIC, SIPR-α, TSP-1, and CD47. Results The hemorheology of psoriatic patients to be abnormal, and aging and deformed erythrocytes increased in the blood. Red cell and leukocyte from psoriasis were more likely to induce psoriasis when comparing with that of from the healthy volunteers, and the effect of red cell was more strong. When splenectomy, mice were also easy to induce psoriasis, demonstrating by the skin lesion, inflammatory factors and histopathology which all similar with psoriasis patients. Psoriasis spleen showed an increased red pulp and white pulp, and increased CD-11b, SPIC, TSP-1 and decreased SPRP-α, CD47 showed marginal change, indicated that the weakening of the “eat me” function of spleen macrophages phagocytizing aging and deformed erythrocytes, resulting in the dysfunction of spleen filtration and the increase of aging and deformed erythrocytes in the body. Additionally, the decreased oxygen-carrying capacity and the declined antioxidant capacity of those erythrocytes led to the hypoxia environment, making psoriasis more likely to be induced. Conclusion These findings demonstrate that spleen filtration dysfunction contributes to the pathogenesis of psoriasis and suggest that improving it may be an effective therapy for psoriasis and control its relapse.

This systematic review aims to assess the effects and safety of Chinese herbal medicines (CHMs) in the management of rhinosinusitis (RS); inform clinicians of the current state of the evidence; identify the best available evidence; and suggest further directions for research. Five English and four Chinese language databases, and four clinical trial registries were searched. Eligible studies were randomised controlled trials (RCTs). Participants were diagnosed with RS based on established criteria. Test interventions were CHMs administered orally and/or nasally, excluding injections and displacement techniques. Control interventions included placebos, no additional treatment, and conventional non-invasive treatments including pharmacotherapies and/or nasal irrigation, and/or inhalations. Polyposis and post-surgical recovery were excluded. Outcomes were Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy Endoscopic score (LK), Mucociliary transport time (MTT), Mucociliary transport rate (MTR), quality of life and adverse events (AEs). Risk of bias used the Cochrane tool. Meta-analysis in Review Manager 5.4.1 used random effects for mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Heterogeneity was assessed as I2. Thirty-four RCTs were included, 30 of chronic RS (CRS) and four of acute RS (ARS). These enrolled 3,752 participants. Five RCTs blinded participants. For CRS, comparisons with placebo showed greater improvements in the CHM groups for SNOT-20 and VAS-TNS (total nasal symptoms). Blinded comparisons with pharmacotherapies showed no differences between groups in the degree of improvement for SNOT-20, VAS-TNS, and LM, suggesting these CHMs had similar effects, at least in the short term. In ARS, pooled results found improved scores on VAS-TNS and LK suggesting a benefit for combining these CHMs with pharmacotherapies. Limitations included inadequacies in study design and methodological reporting, and insufficient reporting of AEs. Heterogeneity in some pooled results precluded strong conclusions. Further well-designed studies are needed to test whether the results are replicable. Systematic review registration number: PROSPERO (CRD42019119586).

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap.Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised.Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia.Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

Psoriasis is a chronic inflammatory skin disorder. Although it has been studied extensively, the molecular mechanisms driving the disease remain unclear. In this study, we utilized a tree-based machine learning approach to explore the gene regulatory networks underlying psoriasis. We then validated the regulators and their networks in an independent cohort. We identified some key regulators of psoriasis, which are candidates to serve as potential drug targets and disease severity biomarkers. According to the gene regulatory network that we identified, we suggest that interferon signaling represents a key pathway of psoriatic inflammation.

The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling.We collected the skin tissue biopsies and swabs in both lesional and non-lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high-throughput RNA-sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling.We found that lesional and non-lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a 'core' set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network.We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin.

IL-23/Th17 (IL-17) axis plays a critical role in psoriasis. Rosmarinic acid (RA) was proved the inhibitory effect of T cell infiltration in the skin. However, whether and how RA has beneficial effects on psoriasis did not really know yet. So lipopolysaccharide (LPS)-induced abnormal proliferation Hacat cell line and Imiquimod (IMQ)-induced psoriasis-like mouse dermatitis were used to assess the pharmacological effects and mechanisms of RA by Psoriasis Area Severity Index (PASI) score, histopathology, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The results showed that RA inhibited LPS-induced aberrant expression of Hacat cell line, and significantly alleviated IMQ-induced skin inflammation. Although RA had no obviously effect on the ratio of epidermal Langerhans cell (LC) and LC migration from the skin to the skin draining lymph nodes, RA inhibited the expression of IL-23 in skin lesions, as well as reduced the differentiation of Th17 cells and producing of IL-17A by down regulating the transcriptor factor RORγt and JAK2/Stat3 signal pathway, comparing to IMQ treated group. The findings suggest that RA inhibits psoriasis-like skin inflammation in vivo and in vitro by reducing the expression of IL-23, inhibiting Th17 dominated inflammation and down regulating the Jak2/Stat3 signal pathway.

Background. This study aimed to explore the mechanisms of action of the PSORI-CM01 and Yinxieling formulas in the treatment of patients with psoriasis vulgaris by analyzing gene expression in peripheral blood mononuclear cells (PBMCs). Methods. PBMC samples were collected from 21 patients before and after treatment. The study included nine patients in the PSORI-CM01 treatment group, 12 patients in the Yinxieling treatment group, and nine patients in the healthy control group. Gene expression levels in PBMCs were determined using the Affymetrix gene chip technology. Results. In the PSORI-CM01 group before and after treatment, a total of 668 differentially expressed genes were found, of which 445 were upregulated and 223 were downregulated. Before and after Yinxieling treatment, 657 differentially expressed genes were found, of which 168 were upregulated and 489 were downregulated. Venn analysis showed that 78 genes were not differentially expressed in the PSORI-CM01 group and 74 were not differentially expressed in the Yinxieling group compared with those in the controls. Among these genes, 72 genes were common to both groups, which were the genes on which the two drugs acted jointly. The results of KEGG analysis and Venn analysis on the signalling pathways of drug action in treatment groups showed that haemostasis and pathways involving Rho GTPases were common signalling pathways of drug action in the two groups. Conclusions. By a comparative analysis of the treatment groups, we found that both drugs have a positive effect on patients with psoriasis vulgaris, primarily by regulating the pathways related to platelet activation, aggregation, and blood coagulation. Trial registration: ChiCTR, ChiCTR-TRC-14005185, Registered 8 August 2014, http://www.chictr.org.cn/showproj.aspx?proj=4390

Background To compare the efficacy and safety of PSORI-CM01 granules with Yinxieling tablets in patients with chronic plaque psoriasis (CPP), we plan to conduct a multicentre, randomized, double-blinded, double-dummy, controlled trial. This pilot study was conducted to determine the feasibility and the potential of the protocol for the full-scale randomized controlled trial (RCT). Methods This pilot study was conducted in three centers, and compared PSORI-CM01 granules with Yinxieling tablets in patients with CPP during a 12-week treatment and 3-month follow-up period. The primary efficacy endpoint was the decrease of the psoriasis area severity index (PASI) at week 12. The secondary outcome measures included reduction rates of PASI, pruritus scores on the Visual Analogue Scale (VAS), body surface area (BSA), and the Dermatology Life Quality Index (DLQI). Safety was assessed via the incidence of adverse events (AEs) in each treatment group. Results A total of 211 patients were screened, and 63 subjects who met the inclusion criteria were randomised to PSORI-CM01 granule group (N=31) or Yinxieling tablets group (N=32) while 39 subjects finished the study. The primary outcome measure showed a mean decrease of PASI of 2.03 in the PSORICM01 group compared to 0.89 in the Yinxieling group at week 12. Except for the VAS score (t=-2.261, P=0.027), the secondary outcomes showed no significant improvement from baseline in both groups at week 12. No safety or tolerability concerns related to the drugs were observed in either group. Conclusions This pilot study showed that the RCT is feasible for randomization, patient recruitment, and assessment. Major strategies are necessary to reduce the patient dropout rate before conducting the full RCT. In this pilot study, the PSORI-CM01 granule exhibited greater potential for development compared to its original formula (Yinxieling tablets) for the treatment of CPP.

Background Poria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM). Objective The purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials. Methods English (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration’s procedures. Stata software (13.0) was used for data analysis. Results Seventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87). Conclusion Evidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated. Trail registration This review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635).

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography–mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

Background Increasing antibiotic resistance has motivated interest in non-antibiotic prophylaxis of recurrent urinary tract infections (rUTI). Objectives To conduct a systematic review of the current state of evidence of acupuncture for uncomplicated rUTI in women. Search strategy Nine databases (PubMed, Embase, CENTRAL, CINAHL, AMED, CBM, CNKI, CQVIP, Wanfang) were searched from inception to February 2019. Selection criteria Randomised controlled trials (RCTs) evaluating the effects of acupuncture and related therapies for prophylaxis or treatment of uncomplicated rUTI in women were included. Data collection and analysis Risk of bias was assessed, and the quality and strength of evidence evaluated using the GRADE framework. Results were reported as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). Main results Five RCTs involving 341 participants were included. Methodological quality of studies and strength of the evidence were low to moderate. The chance of achieving a composite cure with acupuncture therapies was greater than that with antibiotics (three studies, 170 participants, RR 1.92, 95% CI 1.31-2.81, I2 = 38%). The risk of UTI recurrence was lower with acupuncture than with no treatment (two studies, 135 participants, RR 0.39, 95% CI 0.26-0.58, I2 = 0%) and sham acupuncture (one study, 53 participants, RR 0.45, 95% CI 0.22-0.92). Conclusions Acupuncture appeared to be beneficial for treatment and prophylaxis of rUTIs, noting the limitations of the current evidence. Given the growing challenge of antibiotic resistance, there is a need for high-quality RCTs of non-pharmacological interventions such as acupuncture. Tweetable abstract This review found that acupuncture may improve treatment and prevent recurrence of urinary tract infection in women.

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehe...

Conventional immunosuppressants cause side effects and do not prevent the recurrence of autoimmune diseases. Moreover, they may not inhibit autoimmunity mediated by pathogenic memory T-cells. Dihydroartemisinin (DHA) has been shown to regulate autoimmunity. However, it remains unknown whether DHA impacts psoriasis and its recurrence. The objective of this study was to determine therapeutic effects of DHA on psoriasis and its relapse as well as its underlying mechanisms. Methods: We established animal models of imiquimod (IMQ)-induced psoriasis-like wild-type mice and humanized NSG mice receiving lesional human skin from patients with psoriasis. Many immunoassays, including immunohistochemistry, flow cytometry, quantitative RT-PCR and Western blotting, were performed. Results: We found that DHA not only ameliorated acute skin lesion of psoriatic mice, but also alleviated its recurrence by diminishing CD8+ central memory T (TCM) and CD8+ resident memory T (TRM) cells. It attenuated epidermal pathology and T-cell infiltration in the skin of IMQ-induced psoriatic mice while suppressing expression of IL-15, IL-17 and other proinflammatory cytokines in the skin. Surprisingly, DHA reduced the frequency and number of CD8+, but not CD4+, subset of CD44highCD62Lhigh TCM in psoriatic mice, whereas methotrexate (MTX) lowered CD4+, but not CD8+, TCM frequency and number. Indeed, DHA, but not MTX, downregulated eomesodermin (EOMES) and BCL-6 expression in CD8+ T-cells. Furthermore, DHA, but not MTX, reduced the presence of CD8+CLA+, CD8+CD69+ or CD8+CD103+ TRM cells in mouse skin. Interestingly, treatment with DHA, but not MTX, during the first onset of psoriasis largely prevented psoriasis relapse induced by low doses of IMQ two weeks later. Administration of recombinant IL-15 or CD8+, but not CD4+, TCM cells resulted in complete recurrence of psoriasis in mice previously treated with DHA. Finally, we demonstrated that DHA alleviated psoriatic human skin lesions in humanized NSG mice grafted with lesional skin from psoriatic patients while reducing human CD8+ TCM and CD103+ TRM cells in humanized mice. Conclusion: We have provided the first evidence that DHA is advantageous over MTX in preventing psoriasis relapse by reducing memory CD8+ T-cells.

Psoriasis is a chronic and refractory inflammatory and autoimmune-mediated cutaneous disease affecting approximately 2%–3% of the global population. Most of the current therapies could relieve symptoms rapidly, while the side effects cannot be negligible. Hence, it is urgent to explore much safer and more effective treatments. In the current work, we evaluated the potential beneficial effect of Punica granatum peel polysaccharides (PPPs) in an imiquimod-elicited psoriasis-like mouse model and unraveled their mechanism of action. Firstly, PPPs were isolated from P. granatum peels, and then the molecular weight was determined and monosaccharide analysis was performed. The results revealed that PPPs significantly ameliorated psoriasis-like skin lesions and reduced the Psoriasis Area and Severity Index (PASI) scores and transepidermal water loss (TEWL). PPPs also attenuated the expressions of CD3 and Ki67 in psoriasis-like mouse skin and suppressed the serum or skin levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-1β, IL-8, IL-17, and IL-23. Moreover, PPPs were able to upregulate the mRNA and protein expressions of aquaporin-3 (AQP3) and filaggrin (FLG) in the skin of mice. In addition, PPPs inhibited the NF-κB and STAT3 signaling pathways. Overall, these results indicated that PPPs ameliorated the symptoms of psoriasis through inhibition of the inflammatory cytokines by suppressing the NF-κB and STAT3 signaling pathways and improved skin barrier protection via enhancing AQP3 and FLG. These observations potentially contribute to providing theoretical and experimental evidence for the clinical application of PPPs for psoriasis.

Psoriasis is a chronic and inflammatory skin disorder characterized by inflammation and epidermal hyperplasia. Punicalagin (PUN) is a main active ingredient of pomegranate (Punica granatum L.) peel with multiple biological activities, such as antibacterial, antioxidant and anti-tumor effects. However, the potential effect of PUN on psoriasis remains unknown. In this study, we want to investigate the pharmacological effect of PUN on psoriasis by using imiquimod (IMQ)-induced psoriatic mice model in vivo and tumor necrosis factor a (TNF-α) and interleukin-17A (IL-17A)-stimulated HaCaT cells in vitro. Our results showed that PUN can effectively alleviate the severity of psoriasis-like symptoms. Mechanistically, PUN potently suppresses the aberrant upregulation of interleukin-1β (IL-1β) and subsequent IL-1β-mediated inflammatory cascade in keratinocytes by inhibiting the nuclear factor kappa B (NF-κB) activation and cleaved caspase-1 expression in vitro and in vivo. Taken together, our findings indicate that PUN can relieve psoriasis by repressing NF-κB-mediated IL-1β transcription and caspase-1-regulated IL-1β secretion, which provide evidence that PUN might represent a novel and promising candidate for the treatment of psoriasis.

Guben Xiaozhen prescription (GXP), a prescription of traditional Chinese medicine, has been used to treat skin diseases for a long history and achieved satisfactory therapeutic effects. However, its active ingredients and targets remain to be further elucidated.Identify activity ingredients of GXP for the treatment of chronic urticaria (CU) and further validate the efficacy and targets of the selected component.Firstly, the pharmacokinetics of different disassemble groups of GXP was investigated to screen for active ingredients with improved bioavailability. Then, shared targets between active ingredients and CU were performed by network pharmacology. Finally, the ovalbumin (OVA) induced CU model was used to verify the efficacy and targets of the screened active ingredient.Pharmacokinetic results showed that, compared with sub-division groups, the maximum concentration (CIn this study, integrated pharmacokinetics and network pharmacology methods were established to screen out six effective active ingredients in GXP for the treatment of CU. This study provides a new idea for screening active substances in traditional Chinese medicine.

Background: Psoriasis vulgaris and chronic urticaria are common skin conditions with a significant health burden. Achieving long-term control remains a challenge, and some patients choose Chinese herbal medicine (CHM) to meet this need. Little is known about the motivators and experiences of using CHM for these skin conditions.Objectives: To determine the motivators for choosing CHM, and experience of using CHM for psoriasis vulgaris and chronic urticaria.Methods: We conducted semi-structured interviews with participants who had previously used CHM for these conditions. Interviews were transcribed for data analysis.Results: Twenty participants completed the interviews in Guangzhou (n = 16), China, and Melbourne (n = 4), Australia. Motivators included wanting an alternative to conventional medicine, beliefs about CHM and previous experience. Participants expected that CHM would be safer and could prevent relapse; this expectation was met for some participants. Preparing CHM decoctions was onerous, and CHM granules were more convenient.Conclusion: Beliefs, previous experience of using CHM, desire to prevent relapse, and safety are important motivators for choosing CHM in people with psoriasis vulgaris and chronic urticaria. Further clinical evidence is required to enable patients to make informed clinical decisions. Patient preferences should be considered in the context of available evidence when prescribing CHM.

Summary Psoriasis is an immune-mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, anti-oxidant and anti-cancerous properties. However, it is unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesions and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesions induced by topical administration of IMQ. Kaempferol reduced CD3+ T cell infiltration and gene expression of major proinflammatory cytokines, including interleukin (IL)-6, IL-17A and tumor necrosis factor (TNF)-α, in the psoriatic skin lesion. It also down-regulated proinflammatory nuclear factor kappa B (NF-κB) signaling in the skin. The therapeutic effects were associated with a significant increase in CD4+forkhead box protein 3 (FoxP3)+ regulatory T cell (Treg) frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. Conversely, depletion of CD4+CD25+ Tregs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL-17A+CD4+ T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future.

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.

Background: Skin diseases impair patients’ quality of life (QoL). Psoriasis is of particular concern because it affects multiple facets of patients’ lives.Objective: The aim of this study was to investigate whether having psoriasis was associated with the more severe QoL impairment compared with the other 12 skin diseases, based on the Dermatology Life Quality Index (DLQI).Methods: This multicenter observational cross-sectional study was conducted in 9centers in China. Socio-demographic variables and health history were collected with a standardized form questionnaire. QoL was measured by the DLQI. DLQI scores were compared between patients with psoriasis and without psoriasis using univariate analysis. Then multivariate linear regression was used to related QoL to groups (psoriasis vs. non psoriasis), clinical and socio-demographic characteristics.Results: Of 8,339 included dermatological participants, 1,310 (15.7%) had psoriasis, and 7,029 (84.3%) did not. The QoL of patients with psoriasis was lower than that of patients without psoriasis based on the DLQI score (11.20 ± 7.37 vs 8.12 ± 6.26, P < 0.05). The results of multivariate linear regression indicated the same results when adjusting clinical and socio-demographic characteristics.Conclusion: Patients with psoriasis experience more quality of life impairment than patients without psoriasis. More attention should be paid to patients with psoriasis in dermatological health policy decision.

Background Psoriasis is a chronic immune-mediated skin disease affecting approximately 2–3% of world's population. Fuzhenghefuzhiyang decoction (FZHFZY), a Chinese medicine formula created by Prof. Lu Chuanjian, has been shown to have remarkable anti-psoriasis effect in clinical practice. However, the mechanism of action of FZHFZY is unknown. The purpose of this study was to investigate the protective effects of FZHFZY in psoriasis-like skin inflammation both in vitro and in vivo and elucidate the mechanism of action of FZHFZY. Methods In vivo study, we evaluated the protective effect of FZHFZY in imiquimod-induced psoriasis-like mice model. Results indicated that FZHFZY can obviously decrease psoriasis area and severity index (PASI) scores. FZHFZY also suppressed the mRNA levels of IL-6, TNF-α, IL-23 and IL-8 in the skin and its anti-inflammatory activity may be related to its suppression of the P38/Erk/NF-κB signaling. In addition, immunohistochemistry (IHC) data showed that FZHFZY can suppress the expression of F4/80 which is the marker of macrophages in the psoriasis skin. Therefore, we designed to investigate the roles and underlying mechanisms of FZHFZY in LPS-stimulated RAW264.7 macrophages in vitro. Results Our results revealed FZHFZY treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-6, TNF-α, IL-23 and IL-8, which expression was increased remarkably in the activated RAW264.7 cells. Our results also showed that FZHFZY inhibited the P38/Erk/NF-κB signaling pathways in RAW264.7 cells induced by LPS. Conclusions Taken together, our present study demonstrates that FZHFZY alleviated inflammatory response by suppressing the P38/Erk/NF-κB signaling in imiquimod-induced psoriasis-like mice model and LPS-stimulated RAW264.7.

Psoriasis is a chronic inflammatory skin disease that is associated with multiple coexisting conditions. Extensive literature suggests that psoriasis is a T-cell-mediated condition, and its pathogenesis is related to dysfunction of the immune system. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that have suppressive effects on T cells. MDSCs are present at very low levels in healthy individuals but can substantially expand in tumours or inflammatory conditions. PSORI-CM02, a Chinese medical formula designed based on the Chinese medicine theory (Blood Stasis), has been prescribed extensively for psoriasis therapy and shows a stable clinical effect and safety. This study discusses the mechanisms of MDSCs involved in disease development and therapeutic progress. Our data provides evidence that monocytic myeloid-derived suppressor cells (M-MDSCs) play a role in IMQ-induced psoriatic dermatitis. Functional characterization and correlation analysis indicated that MDSCs are positively correlated with Th17 cells. PSORI-CM02 alleviated IMQ-induced psoriatic dermatitis and suppressed the proliferation of Th17 cells via M-MDSC-induced Arg1 upregulation, suggesting M-MDSCs could be a novel therapeutic target for psoriasis, and PSORI-CM02 exerted its effects via the perturbation of M-MDSCs and Th17 cell crosstalk.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Background Mild‐moderate psoriasis vulgaris is a common dermatological autoimmune condition with limited conventional therapeutic options. Safe and effective adjunct therapies to topical non‐steroidal antipsoriatic therapy are needed. The oral Chinese herbal medicine (CHM) formula PSORI‐CM01 has been evidenced potential antipsoriatic pharmacological activity. This article reports a pilot study which was designed as a double‐blinded, placebo‐controlled randomized controlled trial (RCT) evaluating the effects of PSORI‐CM01 when added to topical calcipotriol cream. Methods People with moderate psoriasis vulgaris were randomized to receive oral PSORI‐CM01 or placebo administered for 12 weeks in combination with calcipotriol. The primary clinical outcome was the change of psoriasis area severity index (PASI) score at week 12 and week 24. Secondary clinical outcomes were PASI75, PASI50, relapse rate, change in body surface area, dermatology life quality index and Skindex29, and adverse events (AEs). Participants’ satisfaction and willingness to repeat were also assessed. Results The pilot study was conducted in Australia and China, 29 participants were randomized with 26 completed the treatment and follow‐up. Participants’ baseline basic characteristics were comparable. No between‐group statistical significance was found on pre‐defined clinical outcome measures, although there seemed a trend of treatment effects favoring the combination of PSORI‐CM01 with calcipotriol. Frequency and severity of AEs were similar between two groups, with no severe AEs reported. Conclusions The design and duration of the study appears feasible. A proper powered RCT with slight adjustments in the methods is needed to reveal the add‐on effects of oral CHM PSORI‐CM01. The experience and results from this pilot study will contribute to the refine of objectives and design of a future study, and assist the sample size calculation for the full‐scale RCT.

N6-methyladenosine (m6A) modification, the addition of a methylation decoration at the position of N6 of adenosine, is one of the most prevalent modifications among the over 100 known chemical modifications of RNA. Numerous studies have recently characterized that RNA m6A modification functions as a critical post-transcriptional regulator of gene expression through modulating various aspects of RNA metabolism. In this review, we will illustrate the current perspectives on the biological process of m6A methylation. Then we will further summarize the vital modulatory effects of m6A modification on immunity, viral infection, and autoinflammatory disorders. Recent studies suggest that m6A decoration plays an important role in immunity, viral infection, and autoimmune diseases, thereby providing promising biomarkers and therapeutic targets for viral infection and autoimmune disorders.

Treg cells are essential for re-establishing self-tolerance in lupus. However, given that direct Treg therapies may be inadequate to control autoimmunity and inflammation, a strategy of inducing or expanding endogenous Treg cells in vivo may be a good option. Macrophages are main tissue-infiltrating cells and play a role in promoting Treg differentiation while paeoniflorin (PF), a monoterpene glycoside, exhibits anti-inflammatory and immunoregulatory effects. Here, we studied the effects of PF on CD4

Background Many previous studies have reported factors that contribute to health-related quality of life (HRQoL) for a single skin disease. However, little is known about generalized factors associated with HRQoL across skin diseases. The objective of this study was to investigate overall HRQoL, and to identify factors related to severely impaired HRQoL among patients with 16 different skin diseases. Methods A cross-sectional study of 9845 patients with skin disease was conducted in 9 hospitals in China. HRQoL was assessed with the Chinese version of the Skindex-29 which measures dermatology-specific health along three domains (symptoms, emotions and functioning). With the published Skindex-29 cut-off scores for severely impaired HRQoL, logistic regression models assessed the relationship between severely impaired HRQoL and demographic/clinical characteristics, with adjustments for different skin diseases. To guarantee the models’ convergence, 16 skin diseases with frequencies of at least 100 were included, and the sample size was 8789. Results Emotions was the most impaired aspect of HRQoL. Co-existing chronic diseases, 3 years or longer duration, and more severity were identified as associated factors for severely impaired HRQoL for each Skindex-29 domain, and for the aggregate. Being female, under 45 years old, and consuming alcohol were associated with a severely impaired emotion domain; Lack of exercise and smoking were associated with severely impaired symptoms and function domains, respectively. Conclusions Skin diseases can affect many facets of HRQoL, but the emotional impairment deserves more attention. In addition to skin disease severity, this study shows that other chronic diseases and long duration are correlated with severely impaired HRQoL for patients with 16 clinical common skin diseases. This suggests the need for increased awareness in treating skin disease as a chronic disease. It also suggests that disease management decisions should consider HRQoL improvement, especially emotional conditions, when making management decisions.

Background: Traditional Chinese medicines (TCMs) have been used to manage psoriasis since thousands of years and are associated with advantages such as long remission period and few side effects. PSORI-CM01 is a clinical TCM formula for treating the blood stasis syndrome of psoriasis vulgaris. It is optimised from Yin Xie Ling, a herbal preparation formulated by the Chinese national medical master Xuan Guowei. In the present study, we used microRNA (miRNA) chip technology to analyse the effects of PSORI-CM01 and Yin Xie Ling on miRNA differential expression in the peripheral blood monocytes of patients with blood stasis syndrome of psoriasis vulgaris.Methods: Blood samples collected from healthy subjects and patients with blood stasis syndrome of psoriasis vulgaris were obtained from the Department of Dermatology in the Guangdong Provincial Hospital of Chinese Medicine. These samples were obtained before and after treatment with PSORI-CM01 or Yin Xie Ling. Differentially expressed miRNAs were analysed by performing miRNA expression microarray to evaluate the mechanisms underlying the effects of the two formulations.Results: It was found that hsa-miR-3184-3p, hsa-miR-3653-3p, hsa-miR-20a-3p, hsa-miR-5681b, and hsa-miR-26a-5p were differentially expressed between the PSORI-CM01 and healthy control groups as well as between the Yin Xie Ling and healthy control groups before treatment, without any significant differences in their expression after treatment. The results revealed that the therapeutic effect of PSORI-CM01 on psoriasis was mediated mainly via the regulation of the adherens junction, thyroid hormone signalling, and proteoglycans in cancer pathways, whereas that of Yin Xie Ling was mediated mainly via the regulation of the endoplasmic reticulum protein processing, Hippo signalling, adherens junction, thyroid hormone signalling, cell cycle, proteoglycans in cancer, p53 signalling, oocyte meiosis, and unsaturated fatty acid biosynthesis pathways.Conclusions: The findings demonstrate that PSORI-CM01 and Yin Xie Ling are beneficial for treating blood stasis syndrome of psoriasis vulgaris through the regulation of hsa-miR-20a-3p and hsa-miR-3184-3p expression and, consequently, through the adherens junction, thyroid hormone signalling, and proteoglycans in cancer pathways.Trial registration: Registration number, ChiCTR-TRC-14005185; Date of registration, 8 August 2014.

Background: Recent studies have shown that patients with psoriasis, a chronic inflammatory skin disorder that may accompany the serious systemic disease, are at risk of developing sudden sensorineural hearing loss. The pathogenesis remains unclear, and the mechanisms of this disorder are difficult to explore in the clinical setting due to psoriasis hearing loss’s infrequent incidence. Here, we aimed to identify key candidate genes that may be involved in the pathogenesis of psoriatic hearing loss. Method: In the present study, through online database and literature review, we utilized microRNA-mRNA network analysis and gene ontology annotation analysis, coupled with experimental data from clinical samples, to investigate the relationship between psoriasis and hearing loss. Results: We identified nine miRNAs implicated in both psoriasis and the auditory system. By using bioinformatics techniques, 12 target genes were identified. Finally, the gap junction beta-2 protein (GJB2) was found to be relevant to both psoriasis and hearing loss. In addition, the expression of connexin 26 (Cx26), encoded by GJB2, was significantly downregulated in psoriatic patients’ plasma (p < 0.0001) and was negatively correlated with psoriasis area and severity index (PASI) clinical score (r, −0.286; p = 0.036). Conclusion: GJB2 is a potential candidate gene for hearing loss in psoriasis.