Corrigendum: Deep sequencing of plasma exosomal microRNA level in psoriasis vulgaris patients.

[This corrects the article DOI: 10.3389/fmed.2022.895564.].

Single cell landscape of parietal epithelial cells in healthy and diseased states.

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.

Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis.

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

Deep Sequencing of Plasma Exosomal microRNA Level in Psoriasis Vulgaris Patients.

Psoriasis is a chronic skin disease affecting 1% to 3% of the world population. Psoriasis vulgaris (PV) is the most common form of psoriasis. PV patients suffer from inflamed, pruritic and painful lesions for years (even a lifetime). However, conventional drugs for PV are costly. Considering the need for long-term treatment of PV, it is urgent to discover novel biomarkers and therapeutic targets. Plasma exosomal miRNAs have been identified as the reliable biomarkers and therapy targets of human diseases. Here, we described the levels of serum exosomal miRNAs in PV patients and analyzed the functional features of differently expressed miRNAs and their potential target genes for the first time. We identified 1182 miRNAs including 336 novel miRNAs and 246 differently expressed miRNAs in serum exosomes of healthy people and PV patients. Furthermore, the functional analysis found differently expressed miRNA-regulated target genes enriched for specific GO terms including primary metabolic process, cellular metabolic process, metabolic process, organic substance metabolic process, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway containing cellular processes, human diseases, metabolic pathways, metabolism and organismal systems. In addition, we found that some predicted target genes of differentially expressed miRNAs, such as CREB1, RUNX2, EGFR, are both involved in inflammatory response and metabolism. In summary, our study identifies many candidate miRNAs involved in PV, which could provide potential biomarkers for diagnosis of PV and targets for clinical therapies against PV.

[Adverse events/adverse reactions of acupoint catgut embedding therapy for psoriasis vulgaris: a systematic review].

OBJECTIVE: To systematically review the occurrence of adverse events/adverse reactions (AEs/ARs) induced by acupoint catgut embedding therapy for psoriasis vulgaris (PV) and its safety. METHODS: Randomized controlled trials, controlled clinical trials, cohort studies, case-control studies, case-series, and case reports concerning the treatment of PV with acupoint catgut embedding therapy were searched from Chinese and English databases from their inception to January 7th, 2021. The AEs/ARs related to acupoint catgut embedding therapy for PV were subjected to descriptive statistics, followed by the analysis of possible reasons. RESULTS: Finally, 16 studies were included, involving 1 158 patients. A total of 79 cases were reported to present with mild to moderate AEs/ARs related to acupoint catgut embedding therapy for PV, and there were no serious AEs/ARs or death cases. The most common AEs/ARs were local redness, swelling, heat, and pain (31.65%,25/79), followed by low-grade fever and fatigue (29.11%,23/79), isomorphic reaction (16.46%,13/79), local induration (13.92%,11/79), and fainting (8.86%,7/79). In terms of embedding materials, catgut (93.67%,74/79) and lumbar puncture needles or other puncture needles (49.37%,39/79) were proved the most common AEs/ARs-inducing factors. The proportion of AEs/ARs resulting from treatment interval≤two weeks (67.09%,53/79) and treatment course≤eight weeks (55.70%,44/79) was relatively high. Because the incidence of AEs/ARs fails to be calcula-ted, it is not yet possible to accurately assess the risk and safety of acupoint catgut embedding therapy for PV. CONCLUSION: Available evidence suggests that in the treatment of PV, acupoint catgut embedding therapy may induce a series of mild to moderate AEs/ARs, so its clinical practice deserves attention. We should strictly grasp its indications and contraindications, and prevent the occurrence of related AEs/ARs by standardizing the operation and improving the embedding materials.

Total Glucosides of Paeony Ameliorate Pristane-Induced Lupus Nephritis by Inducing PD-1 ligands+ Macrophages via Activating IL-4/STAT6/PD-L2 Signaling.

Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Further, it has been reported that PD-1 ligands (PD-Ls) contribute to M2 polarization of macrophages and their immunosuppressive effects. Total glucosides of paeony (TGP), originally extracted from Radix Paeoniae Alba, has been approved in China to treat some autoimmune diseases. Here, we investigated the potentially therapeutic effects of TGP on lupus nephritis in a pristane-induced murine model and explored the molecular mechanisms regulating macrophage phenotypes. We found that TGP treatment significantly improved renal function by decreasing the urinary protein and serum creatinine, reducing serum anti-ds-DNA level and ameliorating renal immunopathology. TGP increased the frequency of splenic and peritoneal F4/80+CD11b+CD206+ M2-like macrophages with no any significant effect on F4/80+CD11b+CD86+ M1-like macrophages. Immunofluorescence double-stainings of the renal tissue showed that TGP treatment increased the frequency of F4/80+Arg1+ subset while decreasing the percentage of F4/80+iNOS+ subset. Importantly, TGP treatment increased the percentage of both F4/80+CD11b+PD-L1+ and F4/80+CD11b+PD-L2+ subsets in spleen and peritoneal lavage fluid as well as the kidney. Furthermore, TGP augmented the expressions of CD206, PD-L2 and phosphorylated STAT6 in IL-4-treated Raw264.7 macrophages in vitro while its effects on PD-L2 were abolished by pretreatment of the cells with an inhibitor of STAT6, AS1517499. However, TGP treatment did not affect the expressions of STAT1 and PD-L1 in Raw264.7 macrophages treated with LPS/IFN-γ in vitro, indicating a possibly indirect effect of TGP on PD-L1 expression on macrophages in vivo. Thus, for the first time, we demonstrated that TGP may be a potent drug to treat lupus nephritis by inducing F4/80+CD11b+CD206+ and F4/80+CD11b+PD-L2+ macrophages through IL-4/STAT6/PD-L2 signaling pathway.

Berberine Promotes Induction of Immunological Tolerance to an Allograft via Downregulating Memory CD8+ T-Cells Through Altering the Gut Microbiota.

Emerging evidence has linked the gut microbiota dysbiosis to transplant rejection while memory T-cells pose a threat to long-term transplant survival. However, it's unclear if the gut microbiome alters the formation and function of alloreactive memory T-cells. Here we studied the effects of berberine, a narrow-spectrum antibiotic that is barely absorbed when orally administered, on the gut microbiota, memory T-cells, and allograft survival. In this study, C57BL/6 mice transplanted with islets or a heart from BALB/c mice were treated orally with berberine. Allograft survival was observed, while spleen, and lymph node T-cells from recipient mice were analyzed using a flow cytometer. High-throughput sequencing and qPCR were performed to analyze the gut microbiota. CD8+ T-cells from recipients were cultured with the bacteria to determine potential T-cell memory cross-reactivity to a specific pathogen. We found that berberine suppressed islet allograft rejection, reduced effector CD8+CD44highCD62Llow and central memory CD8+CD44highCD62Lhigh T-cells (TCM), altered the gut microbiota composition and specifically lowered Bacillus cereus abundance. Further, berberine promoted long-term islet allograft survival induced by conventional costimulatory blockade and induced cardiac allograft tolerance as well. Re-colonization of B. cereus upregulated CD8+ TCM cells and reversed long-term islet allograft survival induced by berberine plus the conventional costimulatory blockade. Finally, alloantigen-experienced memory CD8+ T-cells from transplanted recipients rapidly responded to B. cereus in vitro. Thus, berberine prolonged allograft survival by repressing CD8+ TCM through regulating the gut microbiota. We have provided the first evidence that donor-specific memory T-cell generation is linked to a specific microbe and uncovered a novel mechanism underlying the therapeutic effects of berberine. This study may be implicated for suppressing human transplant rejection since berberine is already used in clinic to treat intestinal infections.

Comparison of PSORI-CM01 granules and Yinxieling tablets for patients with chronic plaque psoriasis: a pilot study for a randomized, double-blinded, double-dummy, multicentre trial.

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.

Metabonomics Study on Serum Characteristic Metabolites of Psoriasis Vulgaris Patients With Blood-Stasis Syndrome.

Psoriasis is a chronic, refractory, systemic inflammatory skin disease. Traditional Chinese medicine (TCM) shows unique advantage in the treatment of psoriasis based on syndrome differentiation. An untargeted high-throughput metabonomics method based on liquid chromatography coupled to mass spectrometry was applied to study the serum metabolic characteristics in different TCM syndrome types in patients with psoriasis vulgaris (PV), and to discover potential serum biomarkers for its pathogenesis on the endogenous metabolite differentiation basis. The serum metabolic profiles of 45 healthy controls and 124 patients with PV (50 in the blood-stasis group, 30 in the blood-heat group, and 44 in the blood-dryness group) were acquired. The raw spectrometric data were processed using multivariate statistical analysis, and 14 biomarkers related to TCM syndrome differentiation and psoriasis types were screened and identified. The blood-stasis syndrome group showed abnormal lipid metabolism, which was characterized by a low level of phosphatidylcholine (PC) and a high level of lysophosphatidylcholine (LPC). We propose that platelet-activating factor can be applied as a potential biomarker in clinical diagnosis and differentiation of PV with blood-stasis syndrome. The difference in the serum metabolites among PV types with different TCM syndromes and healthy control group illustrated the objective material basis in TCM syndrome differentiation and classification of psoriasis.

The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review.

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.

Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis.

BACKGROUND: Circulating exosomal microRNAs modulate not only cancer cell metabolism but also the immune response, and therefore plasma exosomal microRNAs might have the potential to be the biomarkers for a number of immune disorders. OBJECTIVE: This study was conducted to identify the common mechanisms among psoriatic arthritis (PsA), psoriasis vulgaris (PV), rheumatoid arthritis (RA), and gouty arthritis (GA). The common expressed plasma exosomal microRNAs in these diseases were determined. METHODS: The expression of microRNAs derived from plasma exosome of patients with PsA (n=30), PV (n=15), RA (n=15), GA (n=15), and healthy controls (n=15) was evaluated via sequencing. Function analysis of common expressed microRNAs was conducted by the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Coexpression analysis was conducted to identify novel and significant genes and proteins by using the Search Tool for the Retrieval of Interacting Genes (STRING). A systematic literature review was conducted to uncover the role of the common microRNAs in the pathogenesis of PsA, PV, RA, and GA. RESULTS: A total of 36 common expressed microRNAs were detected in patients with PsA, PV, RA, and GA. The most significantly enriched biological processes, cellular components, and molecular functions were "homophilic cell adhesion via plasma membrane adhesion molecules," "CCR4-NOT complex," and "calcium ion binding," respectively. "Antigen processing and presentation" was the most significantly enriched pathway. A total of 91 validated coexpressed gene pairs were identified and 16 common expressed microRNAs and 85 potential target genes were screened based on Cytoscape. Of 36 common expressed microRNAs, 5 microRNAs, including hsa-miR-151a-3p, hsa-miR-199a-5p, hsa-miR-370-3p, hsa-miR-589-5p, and hsa-miR-769-5p, were considered to be connected with the common pathogenesis of PsA, PV, RA, and GA. Systemic review revealed that the roles of these 5 microRNAs are related to immune disorder and bone injury, which matches the conclusion from GO and KEGG analyses. CONCLUSION: (1) Both immune disorder and bone metabolic dysregulation could be the shared mechanism in the development of PsA, PV, RA, and GA. (2) Immune dysfunction is involved in GA. Our study may shed new light on the diagnosis and treatment strategy of these autoimmune diseases and GA, which warrants further studies.

Acupuncture for cancer pain: protocol for a pilot pragmatic randomised controlled trial.

INTRODUCTION: Although acupuncture has been recommended for alleviating cancer pain by clinical guidelines, the level of the supporting evidence needs to be improved. A pragmatic randomised controlled trial (pRCT) in a hospital setting would provide real-world assessments of the overall clinical effects of acupuncture. This pilot trial aims to explore the feasibility and provide data for sample size calculations for a pRCT evaluating the effectiveness of acupuncture as an adjunctive therapy to routine medical care for cancer pain. METHODS AND ANALYSIS: Thirty patients with cancer admitted to the oncology department with moderate or severe pain will be recruited. Participants will be randomised at a ratio of 1:1 to the adjunctive acupuncture group or a control group which receives routine pain management without acupuncture. The standardised section of the acupuncture protocol will be developed based on the results of reviews of the literature, recommendations in clinical guidelines and interviews with clinical experts. The acupuncturist will be allowed to tailor the protocol according to the individual situation of each participant. Primary outcomes relevant to the feasibility of conducting a fully powered trial include: numbers and proportions of participants recruited, screened, consented and randomised; numbers and reasons for withdrawals and dropouts; numbers and types of adverse events; feasibility of implementing the trial procedures; evaluation of the comprehensiveness and ease-of-use of the case report form. Secondary outcomes are clinical measurements of the effectiveness of the treatment that are intended for use in the full-scale trial. Analysis of feasibility will be descriptive and pain intensity measures will be analysed using mixed-effects regression. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (approval no: Z2017-184-01) and RMIT University Human Research Ethics Committee (reference no: 21361). Results will be disseminated in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls. TRIAL REGISTRATION NUMBER: ChiCTR1800017023.

PSORI-CM02 alleviates IMQ-induced mouse dermatitis via differentially regulating pro- and anti-inflammatory cytokines targeting of Th2 specific transcript factor GATA3.

The IL-17-producing CD4+ T cell and γδT cells play critical roles in the pathogenesis of psoriasis (PS). PSORI-CM02 is a representative herbal formula for the treatment for PS in South China. It was confirmed to improve PS without obvious side effects in the clinic. Here we sought to clarify whether and how PSORI-CM02 regulates T cell differentiation and functions in IMQ-induced psoriasis-like BALB/c mouse model. Mice pre-treated 3 days with PSORI-CM02 significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections. CD3 and CD4 positive T cells were also fewer in the skin lesions of PSORI-CM02 groups, comparing to control group. PSORI-CM02 also decreased pro-inflammatory IFNγ mRNA and IL-17 A mRNA, while increased IL-4 mRNA in mouse skin lesions. In skin draining lymph nodes (DLN), PSORI-CM02 reduced the ratio of γδT cells and inhibited their function of producing IL-17 A. Nevertheless PSORI-CM02 had no effects on the ratio of total TCRß+T cells and CD4 + T cells. But it regulated CD4 + T helper cells differentiation, and resulted in the decreasing percentage of IFNγ producing Th1 cells and IL-17 A producing Th17 cells, while increasing the ratio of IL-4 producing Th2 cells in DLN. Further data showed that PSORI-CM02 promote expression of Th2 specific transcript factor GATA3, but had no effects on T-bet and RORγ. Thus, we tentatively interpret that PSORI-CM02 impairs IMQ-induced psoriasis by promoting Th2 cell response targeting of GATA3.

Formula PSORI-CM01 inhibits the inflammatory cytokine and chemokine release in keratinocytes via NF-κB expression.

Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced. Th1 related cytokine IFN-γ and Th17 related cytokine IL-17/IL-22 was used to induce inflammatory models on human keratinocyte cell line HaCaT in vitro, respectively. PCM01CS significantly reduced IFN-γ induced mRNA expression of IL-6, IL-12 and CXCL-10, reduced IL-6 and CXCL-10 release into HaCaT supernatant. 20ng/ml IL-17/IL-22 co-stimulation significantly upregulated expression of IL-6, IL-8 and CCL20 mRNA expression in HaCaT cells, PCM01CS significantly inhibit these cytokines expression both in mRNA and in protein levels. Finally, PCM01CS could obviously inhibit nuclear NF-κB p65 expression which activated by IFN-γ and IL-17/IL-22 stimulation. Thus, our new findings reveal that Formula PSORI-CM01 may possess therapeutic action on psoriasis by inhibiting inflammatory within skin environments.

Roles of microRNAs in psoriasis: Immunological functions and potential biomarkers.

MicroRNAs (miRNAs) are small non-coding RNA molecules, which function in RNA silencing and post-transcriptional regulation of gene expression. Psoriasis is an inflammatory skin disease characterized by the dysfunction of keratinocytes, with the immune dysregulation. We reviewed the recent studies on the roles of miRNAs in psoriasis and showed that miRNAs play key roles in psoriasis, including the regulation of hyperproliferation, cytokine and chemokine production in keratinocyte, as well as mediating immune dysfunction in psoriasis. Furthermore, miRNAs, particularly, circulating miRNAs may serve as novel biomarkers for diagnosis, monitoring therapy response and reflecting the disease severity. Thus, targeting specific miRNAs may be used to develop new therapeutic methods for psoriasis.

Role of an imbalanced miRNAs axis in pathogenesis of psoriasis: novel perspectives based on review of the literature.

BACKGROUND: Specific profile of microRNAs (miRNAs, miR) expressed in psoriasis has been identified in the past few years, while the studies on roles and molecular mechanisms of these miRNAs are still on the way. In our previous study, four specific miRNAs (miR-31, miR-203, hsa-miR-99a and miR-125b) were found to be specifically altered in psoriatic lesions.We therefore conducted a systematic literature review in this study to reveal the role of these miRNAs in the pathogenesis of psoriasis in order to inform future research. METHODS: The related articles indexed in PubMed (MEDLINE) database were searched and analyzed. We identified eligible studies related to the mechanism research of miR-31, miR-203, hsa-miR-99a and miR-125b in psoriasis or psoriatic lesional skin from inception up to July 2016. The experts in the field of miRNAs and Psoriasis were involved in analysis process. RESULTS: Both miR-31 and miR-203 are dramatically upregulated in psoriatic lesions. The former plays the pro-proliferative, pro-differentiative and pro-inflammatory roles and the latter holds the potentials for anti-proliferation, pro-inflammation and pro-differentiation in psoriatic keratinocytes. Conversely, both hsa-miR-99a and miR-125b are significantly downregulated in psoriatic skin. These two miRNAs are able to inhibit proliferation while promote differentiation of psoriatic keratinocytes, and miR-125b can also suppress inflammation in psoriatic lesions. By analyzing the contexts related to these miRNAs, we found that each of them does not act alone but rather work in concert with other miRNAs. The imbalance between miR-31/miR-203and hsa-miR-99a/miR-125b may contribute to the intense proliferation and abnormal differentiation of psoriatic keratinocytes, which is a characteristic of pathogenesis of psoriasis. CONCLUSION: An imbalanced miRNAs axis was for the first time outlined. Apparently, upregulation of miR-31/miR-203 and downregulation of hsa-miR-99a/miR-125b work together in concert to facilitate the development of psoriasis pathogenesis. Further work in this field holds the potentials to open a new way to study psoriasis.

Structural characterization and macrophage immunomodulatory activity of a novel polysaccharide from Smilax glabra Roxb.

A novel heteropolysaccharide (SGRP1) with great immunomodulatory activity was isolated from the root of Smilax glabra Roxb. by hot water extraction. Physical and chemical analyses showed that SGRP1 had an average molecular weight of 1.26×104Da and was composed of mannose, fucose and glucose in molar ratio of 1.00:3.09:39.41. The glycosidic linkage types of SGRP1 were proven to be (1→3)-linked -α-l-Fuc, (1→3)-linked-α-l-Man, (1→)-linked-α-d-Glc, and (1→6)-linked-α-d-Glc. The in vitro immunomodulatory assays demonstrated that SGRP1 could evidently promote the phagocytosis and increase macrophage-derived biological factors including nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) secretion via JNK and ERK signaling pathways and NLRP3 inflammasome signaling pathway. The data supported that SGRP1 had immunomodulatory potential through activating macrophages and enhancing host immune system function, which enabled it to be a novel immunomodulator for application in immunological diseases or functional food.

Memory Impairment, Dementia, and Alzheimer's Disease in Classical and Contemporary Traditional Chinese Medicine.

OBJECTIVES: To identify and analyze records of the treatment of dementia and memory disorders in the classical Chinese medical literature that were consistent with the signs and symptoms of Alzheimer's disease (AD), with the aim of determining which traditional medicines have histories of use for these disorders. METHODS: Encyclopedia of Traditional Chinese Medicine (Zhong Hua Yi Dian), a database of more than 1000 classical and premodern Chinese medical books, was systematically searched. Search terms were identified from dictionaries, medical nomenclatures, guidelines, and specialist clinical manuals on aging, neurology, or brain disorders. Inclusion and exclusion criteria were used to identify citations of conditions whose signs and symptoms were consistent with the clinical features of AD. Passages of text identified by these terms were copied to Microsoft Excel spreadsheets, together with the identity of the source book and all relevant information on the disorder and the intervention. Each distinct passage of text was considered a citation. The frequencies of the traditional formulas used as interventions and their constituent ingredients were calculated. RESULTS: The selection criteria identified 1498 citations of dementia and memory impairments derived from 277 different books written from circa 363 to 1945 AD. In 91 of these citations, memory impairment was associated with aging and was broadly consistent with the clinical features of AD. Although the interventions varied in name, Poria cocos, Polygala tenuifolia, Rehmannia glutinosa, Panax ginseng, and Acorus species consistently appeared as ingredients in multiple formulas for memory impairment in the context of aging. CONCLUSIONS: Memory impairment in older age was a recognized condition in the classical literature. Many of the traditional medicines frequently used as ingredients in classical formulas for memory impairment consistent with clinical features of AD remain in contemporary use, and experimental studies suggest biological activities relevant to AD.

Formula PSORI-CM01 eliminates psoriasis by inhibiting the expression of keratinocyte cyclin B2.

BACKGROUND: Psoriasis is a chronically recurrent inflammatory skin disease, modern medicine could achieve good therapeutic effect, but these treatments led to recurrence of the psoriasis, more severe symptoms due to damaging skin barrier. Traditional Chinese medicine is a useful alternative therapies. The purpose of this study was to explore the mechanism of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, in eliminating psoriasis by studying its effects on inhibiting epidermal hyperplasia. METHODS: Imiquimod induced psoriasis-form mice model was used to determine the efficacy of PSORICM-01 by assessing the improvement of hyperplasia in epidermal and dermal skin, cyclin B2 expression in skin was detected by immunochemistry. Human keratinocyte cell line HaCaT stimulated by LPS or not was used to research molecular mechanisms of PSORIMCM-01 as in vitro model. The inhibition of proliferation of HaCaT was determined by MTT assay, BrdU assay and real-time cell analysis (RTCA). Cell cycle distribution was detected by flow cytometry. Real-Time PCR and western blot analysis was performed to quantify the mRNA and protein expression levels, respectively. The ability of PSORICM-01 to inhibit proliferation of cyclin B2 overexpressed HaCaT cell were also investigated. RESULTS: PSORI-CM01 significantly inhibited epidermal hyperplasia in IMQ mice lesion skin, and reduced expression of epidermis cyclin B2. Serum containing PSORI-CM01 dramatically inhibited keratinocyte HaCaT cell proliferation, no matter stimulated by LPS or not. FACS analysis showed ability of PSORICM-01 to arrest cell cycle in the G2/M phase. Additionally, PSORI-CM01 significant downregulated mRNA and protein expression of cyclin B2, and over-expression of cyclin B2 antagonized the anti-proliferative effect of PSORI-CM01 on HaCaT cells. CONCLUSIONS: PSORI-CM01 inhibits epidermal hyperplasia in imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro. Our results indicate that PSORI-CM01 may possess therapeutic potential for psoriasis by inhibiting keratinocyte proliferation through downregulation of cyclin B2.