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Background Radix Astragali is a medicinal herb with various physiological activities and a long history of use dating back 2,000 years. Tens of thousands of tonnes of Radix Astragali are sold worldwide each year. Their clinical applications are affected by many factors, including geographical origin. Conventional microscopic examination and chromatography-based fingerprinting of Radix Astragali roots are tedious extraction procedures, resulting in loss of their original form. Raman spectroscopy is a non-invasive and non-destructive technique that can be used in the in-situ analysis of herbal samples. In this study, we investigated the potential of a 1064 nm-excited portable Raman spectrometer and data fusion for the rapid analysis of Radix Astragali samples from different sources and origins.Results A portable Raman spectrometer was used for the analysis of certified and counterfeit Radix Astragali samples as well as for the determination of their geographical origin. Dispersive Raman scattering, excited at 1064 nm, produced minimal fluorescence background and facilitated easy detection of the weak Raman signal. By moving the Raman probe point-by-point from the centre of the sample to the margin, the spectral fingerprints, composed of dozens of Raman spectra representing the entire Radix Astragali samples, were obtained. Principal component analysis and partial least squares discriminant analysis (PLS-DA) were applied to the Radix Astragali spectral data to compare the classification results, leading to efficient discrimination between genuine and counterfeit Radix Astragali. However, there were high similarities among Radix Astragali samples from different regions owing to the similarities in their main chemical compositions. In the PLS-DA model using data fusion combined with different pre-processing methods, the samples from Shanxi Province were separated from those belonging to other habitats.Conclusion Using a combination of 1064-nm excitation and point-by-point spectral collection mode, the fused Raman spectral data can effectively improve the recognition rate and accuracy of herbal samples, which can be a valuable tool for the identification of genuine medicinal herbs.

Overexpression of RAD51 is found in many cancers including breast cancer and is associated with poor survival. Compared with normal cells, RAD51 promoter is hyperactive in cancer cells indicating that RAD51 is transcriptionally activated. However, little is known about the mechanisms and factors involved in RAD51 transcription regulation. Transcription corepressor, C-terminal binding protein 1 (CtBP1), is an oncogene repressing a panel of tumor suppressors transcription, which contributes to cancer progression. In this study, immunohistochemistry (IHC) revealed that RAD51 expression was positively correlated with CtBP1 expression in breast cancer patient tissues; short hairpin RNA-mediated CtBP1 depletion, chromatin immunoprecipitation, and dual-luciferase reporter assays showed that CtBP1 activated RAD51 transcription in breast cancer cells. Depletion of CtBP1 increased breast cancer cells' sensitivity to cisplatin and, in turn, expression of exogenous RAD51 in the CtBP1-depleted breast cancer cells increased resistance to cisplatin. The results demonstrated that CtBP1 conferred breast cancer cells resistance to cisplatin through transcriptional activation of RAD51.

Diabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties.To research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers.Chemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 - 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action.The expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using HE, qRT-PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions.High levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects.In vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Background: Eczema is the most common allergic skin disorder in the world. The treatment of eczema with western medicine generally involves antihistamines, antibiotics, glucocorticoids, and immunomodulatory preparations, which are limited by common relapse events following drug withdrawal. Many traditional Chinese medicines have demonstrated significant effects on eczema; however, high-quality clinical studies are lacking.Objectives: We performed a multi-center, randomized, double-blind, clinical trial to evaluate the efficacy and safety of a Chinese herbal medicine, Qinzhuliangxue (QZLX) granules, and its effect on recurrence of eczema.Methods: A total of 342 patients with eczema who met the inclusion criteria were recruited and randomly divided into a traditional Chinese medicine (TCM) treatment group, a Western medicine (WM) treatment group, and a TCM plus WM treatment group, according to random numbers generated using the central stratified zone group random method. The Eczema Area and Severity Index (EASI) score and the level of pruritus were set as the primary outcome measures, and the Dermatology Quality of Life Index (DLQI) score served as the secondary outcome measure. In this study, a two-sided p-value less than 0.05 was considered statistically significant. Results: The median EASI score and the pruritus level at baseline were not statistically significant. However, as the treatment period progressed, the EASI score (including the total score and scores for the head, upper limb, trunk, and lower limb) and pruritus level decreased significantly in all three treatment groups. Repeated measures Analysis of Variance (ANOVA) demonstrated that the DLQI scores in the TCM, WM, and TCM+WM groups decreased significantly over time. Limitations: Basic experiments need to be increased.Conclusions: The Chinese herbal medicine QZLX granules significantly improved the EASI score and decreased the pruritus level in eczema patients, with good safety and no obvious adverse reactions.Trial RegistrationThe protocol for this study was registered with the Clinical Trials database (NCT02517957). Registered 1 May 2015, Xia Shi Surgical Treatment for Eczema Multi-center Clinical Research - Full Text View - ClinicalTrials.gov

Because treatment of diabetic ulcers includes various uncertainties, efficacy assessments are needed and significant. In previous studies, set pair analysis (SPA) has been applied to the efficacy assessments of traditional Chinese medicine (TCM) that pick out uncertainties related to the development and prognosis of disease. Optimized clinical protocols of SPA improve clinical efficacy. In the article, cloud model (CM) is employed to improve SPA, and a novel efficacy assessment method for a treatment of diabetic ulcers is proposed based on the cloud model-set pair analysis (CM-SPA). It is recommended to replace connection degree (CD) with cloud connection degree (CCD) that the efficacy assessment results are shown as normal clouds. Then, three diabetic ulcers patients treated with TCM made importance assessment by both CM-SPA and AHP based SPA. The comparison of assessment results shows that the CM-SPA is efficacious for the efficacy assessment of a treatment for diabetic ulcers and the results will be more scientific and accurate via CM-SPA.

We assessed the roles of Smad7 in skin inflammation and wound healing using genetic and pharmacological approaches. In K5.TGFβ1/K5.Smad7 bigenic (double transgenic) mice, Smad7 transgene expression reversed transforming growth factor (TGF)-β1 transgene-induced inflammation, fibrosis, and subsequent epidermal hyperplasia and molecularly abolished TGF-β and NF-κB activation. Next, we produced recombinant human Smad7 protein with a Tat-tag (Tat-Smad7) that rapidly enters cells. Subcutaneous injection of Tat-Smad7 attenuated infiltration of F4/80+ and CD11b+ leukocytes and α-smooth muscle actin+ fibroblasts before attenuating epidermal hyperplasia in K5.TGFβ1 skin. Furthermore, topically applied Tat-Smad7 on K5.TGFβ1 skin wounds accelerated wound closure, with improved re-epithelialization and reductions in inflammation and fibrotic response. A short treatment with Tat-Smad7 was also sufficient to reduce TGF-β and NF-κB signaling in K5.TGFβ1 skin and wounds. Relevant to the clinic, we found that human diabetic wounds had elevated TGF-β and NF-κB signaling compared with normal skin. To assess the oncogenic risk of a potential Smad7-based therapy, we exposed K5.Smad7 skin to chemical carcinogenesis and found reduced myeloid leukocyte infiltration in tumors but not accelerated carcinogenesis compared with wild-type littermates. Our study suggests the feasibility of using exogenous Smad7 below an oncogenic level to alleviate skin inflammation and wound healing defects associated with excessive activation of TGF-β and NF-κB.

Anti-inflammation medication is one of the most important treatment for people with atopic dermatitis (AD) which presents persistent type 2 inflammation in skin lesions. Interaction between activated keratinocytes and immune cells in AD skin lesions amplifies inflammatory signaling by augmenting production of cytokines, such as keratinocyte-derived thymic stromal lymphopoietin (TSLP) and interleukin-33 (IL-33). Phellopterin is a bioactive compound isolated from ethanol extract of Angelica dahurica root which has been traditionally used for AD therapy in China. In the present study, we showed that Phellopterin possessed anti-type 2 inflammation activity and alleviated AD-like phenotypes including reduction in serum immunoglobulin E (IgE) levels and infiltration of eosinophils and mast cells in the AD-like skin lesions. Further molecular analysis found that Phellopterin suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705, and the expression of TSLP and IL-33 in epidermal keratinocytes of AD-like lesions. In vitro studies in cultured human keratinocytes demonstrated that STAT3 was required for interleukin-4 (IL-4)-induced overexpression of TSLP and IL-33. Phellopterin inhibited IL-4-induced activation of STAT3, which leaded to suppress the STAT3-mediated transcription of TSLP and IL-33. Our study suggested that Phellopterin is an active compound with bioactivities of anti- type 2 inflammation and STAT3 inactivation, thus allowing to be a promising candidate for AD topical therapy.

Multiple factors contribute to the pathogenesis of childhood vitiligo. The characteristics in a different population under modified environmental factors need further reevaluation. The present study aimed to reevaluate the clinical and laboratory features in consequent children vitiligo patients.We retrospectively reviewed consequent children vitiligo patients who visited Children's Hospital of Fudan University (National Children's Medical Center of China). The prevalence rate of thyroid dysfunction, circulating autoantibodies, serum IgE, and associated factors were analyzed.A total of 244 consequent vitiligo patients were included, of which 20 children had personal autoimmune history. Two hundred and nineteen of the 244 patients took a thyroid function test, and the abnormal rate was only 3.7% (8/219). The elevated IgE rate was 31.7% (52/157), the antinuclear antibody (ANA) positive rate was 9.8% (12/123), and the extractable nuclear antigens (ENA) positive rate was 4.4% (4/91), respectively. The elevated IgE was significantly associated with atopic disease history and male gender. Of note, personal autoimmune history showed a significant inverse association with elevated IgE.Thyroid dysfunction rate was low among the consequent children vitiligo patients. Personal autoimmune history was inversely associated with elevated IgE. Various clinical characteristics and pathogenesis might contribute to different long-term outcomes of vitiligo.

Background. Quyu Shengji Formula (QSF), a Chinese medicine formula widely used in the clinic, has proven therapeutic effects on diabetic ulcers. Nevertheless, the potential mechanism of how QSF cures diabetic ulcer remains elusive. Objective. To assess the mechanism of QSF against wound healing defects in diabetes. Methods. Db/db mice were adopted to determine the therapeutic potential of QSF. Further histology analysis was performed by hematoxylin and eosin (H&E) staining. Moreover, the expression patterns of prostaglandin transporter (PGT), prostaglandin E2 (PGE2), and angiogenesis factor vascular endothelial growth factor (VEGF) were evaluated by immunostaining (IHC) analysis, ELISA assay, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot analysis in vivo. Human dermal microvascular endothelial cells (HDMECs) and the shRNA interference technique were used to explore the effects of QSF on cell migration, PGT, PGE2, and angiogenesis factor VEGF in vitro. Results. Applied QSF on the wound of db/db mice significantly accelerated wound closure. Reductions of PGT and elevations of PGE2 and increased angiogenesis factor VEGF levels were shown after QSF treatment in vivo and in vitro. Furthermore, QSF promoted HDMEC migration. Inhibition of the expression of PGT by shRNA reversed phenotypes of QSF treatment in vitro. Conclusion. Taken together, our findings reveal that QSF ameliorates diabetes-associated wound healing defects by abolishing the expression of PGT.

Ethnopharmacological relevance Sheng-ji Hua-yu (SJHY) formula is a traditional Chinese herbal which is effective in treating diabetic ulcers. It has been indicated to accelerate re-epithelialization and healing time of cutaneous wounds in a Streptozotocin (STZ)-induced diabetic mouse model. However, its mechanisms remain undetermined. Aim of the study To reveal the molecular mechanisms of SJHY formula in treating diabetic wounds through transcriptional profiling and circRNA-miRNA-mRNA network analysis clues. Materials and methods Protein expressions of tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-1β in skin tissues of wounds from SJHY formula-treated and untreated mice were analyzed by Bio-Plex assay. Differentially expressed (DE) genes were detected by whole transcriptome sequencing (RNA-seq). Using predicted miRNA targets, circRNA-miRNA-mRNA networks were constructed. Furthermore, quantitative real-time PCR (qRT-PCR) was utilized to validate the circRNA-miRNA-mRNA networks. Results Bio-Plex assay illustrated that the protein expressions of TNF-α, IL-1β, IL-6 were downregulated in SJHY formula-treated diabetic wounds compared with untreated wounds. RNA-seq identified 11 DE circRNAs and 476 DE mRNAs between SJHY formula-treated and diabetic mice, including 4 upregulated and 7 downregulated circRNAs, 311 upregulated and 165 downregulated mRNAs. CircRNA-Krt13/miR-665–3p/Itga3 and circRNA-Krt14/miR-706/Mylk4 pathways were built, which may contribute to the healing of SJHY formula-treated diabetic wounds. Conclusions Overall, this study suggests that these 2 circRNA-miRNA-mRNA networks are potential biomarkers for evaluation of SJHY formula efficacy in diabetic wound healing, which provides evidence to support its clinical applications.

Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms. There are three common pathways leading to psoriasis: (1) Th17 cells secrete IL-17, which is stimulated by IL-23; (2) Th1 cells secrete IL-21, TNF-[Formula: see text] and IFN-[Formula: see text], with the help of Th17 cells; (3) Th22 cells secrete IL-22 under the stimulation of Th17 cells. Clinical and experiment data indicate that TCM could modify psoriasis by antagonizing or regulating interleukin and IL-23/IL-17 axis to inhibit the main pathways.

Importance The prevalence and characteristics of short stature (SS) among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies. Thus far, there have been no accurate estimates of the prevalence of SS in China. Objective To analyze the prevalence of SS among children in China and to explore the influences of sex, area, age, study year, and study site on prevalence rates. Methods Relevant literature was identified by searching the following databases: PubMed, Embase, The Cochrane Library, Chinese Biomedical Literature, China Knowledge Resource Integrated, WeiPu, and WanFang databases. Meta‐analysis was carried out using STATA 11.2. Results This meta‐analysis included 39 studies with 348 326 Chinese participants; the studies covered 20 provinces, municipalities, and autonomous regions. The pooled prevalence of SS was 3.2% (95% confidence interval [CI], 2.6%–3.7%; I 2 = 99.8%). The prevalence of SS in boys and girls were 3.1% (95% CI, 2.5%–3.7%) and 3.2% (95% CI, 2.6%–3.9%), respectively. The sex difference was not statistically significant (P > 0.05). The prevalence of SS was higher in rural areas than in urban areas (4.7% [95% CI, 3.6%–5.8%] vs. 2.8% [95% CI, 2.2%–3.4%]; P < 0.001). The prevalence of SS was higher in West China (5.2%; 95% CI, 4.4%–6.0%) than in Northeast China (0.6%; 95% CI, 0.3%–0.8%), East China (2.3%; 95% CI, 1.9%–2.8%), or Central China (2.9%; 95% CI, 1.9%–3.9%). Interpretation The prevalence of SS among children was higher in western and rural areas of China. Close attention to children’s growth and development is needed to prevent the occurrence of SS.

Objective. To determine whether immunological serum markers IFN-γ, IL-4, IL-17, IL-23, IL-6, TNF-α, and IL-10 are elevated or decreased in patients compared with healthy controls.Methods. A complete search of the literature on this topic within the past 30 years was conducted across seven databases. Seventeen studies including 768 individuals were identified. Differences in serum marker levels between subjects and controls were pooled as MDs using the random-effects model.Results. The pooled MDs were higher in patients than in healthy controls for IFN-γ(MD 24.9, 95% CI 12.36–37.43), IL-17 (MD 28.92, 95% CI 17.44–40.40), IL-23 (MD 310.60, 95% CI 4.96–616.24), and TNF-α(MD 19.84, 95% CI 13.80–25.87). Pooled IL-4 (MD −13.5, 95% CI −17.74–−9.26) and IL-10 (MD −10.33, 95% CI −12.03–−8.63) levels were lower in patients.Conclusion. The pooled analyses suggest that levels of IFN-γ, IL-17, IL-23, and TNF-αare significantly elevated and that levels of IL-4 and IL-10 are significantly decreased in sera of patients with psoriasis vulgaris of blood-heat syndrome. Measuring progression of blood-heat syndrome of psoriasis vulgaris will require additional high-quality data, with a low risk of bias and adequate sample sizes, before and after antipsoriatic therapy.

Background Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. Methods SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Results Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. Conclusion The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin. Graphical abstract

Chronic ulcer, including diabetic ulcer, varicose ulcer, and pressure ulcer, negatively affects patients’ quality of life. As microbiology plays an important role in the mechanism of pathology for chronic wound healing, this study concentrates on microecology environment of the wound and how Traditional Chinese Medicine (TCM) regulates wound bacteria. Method. The study took wound samples from 35 patients and analyzed bacteria variation before and after TCM treatment by 16s rRNA sequencing. All samples were evaluated from aspects of α-diversity, β-diversity, and Simpson’s Diversity index. Result. After total DNA extraction, PCR, and 16S rRNA sequencing of wound bacteria from 35 individuals, it was discovered that younger patients with shorter course of disease have a higher microbial diversity and were easier to recover from ulcers. Additionally, gender also played a vital role in wound healing, and a significant microbial diversity existed between male and female patients. Conclusion. Patients with chronic ulcers achieved a positive effect after TCM treatment (skin-producing ointment). Mechanistically, TCM helped promote wound healing by regulating the wound microbiota.

Background The potential toxicity of Chinese herbal medicine has attracted more attention in recent years. Jueyin granules (JYG), a polyherbal formula, have been proven to be an effective agent for treating psoriasis in both animal models and clinical research. However, little is known about the possible acute and chronic toxicity of JYG. The objective of this study was to investigate the safety of JYG in ICR mice and Wistar rats. Methods To examine the acute toxicity of JYG, ICR mice were randomly divided into an experimental group and a control group, each comprising 20 mice (10 male and 10 female). The experimental group was fed JYG solution at a dose of 21.5 g/kg, equivalent to 143 times the clinical human dosage, for 14 days, whereas control animals were fed distilled water. In the chronic toxicity test, Wistar rats were divided into four groups, each comprising 40 rats (20 male and 20 female). For 6 months, the experimental animals were given JYG at a dose of 7.5, 3.75 and 1.875 g/kg, whereas control animals were given distilled water. The animals’ body weight, food and water consumptions were monitored weekly. In addition, their biochemical and hematological parameters, histopathology, and body and organ weights were all measured at specific observation time points. Results According to the results of the acute toxicity test, no mortality was found and no abnormal pathological changes in major organs were observed in mice treated with JYG. In the chronic toxicity test, JYG did not cause significant abnormalities in the physiological parameters or pathological changes in the major organs of the rats. Conclusion The results indicated that JYG at the given doses did not induce any harmful effects in animals. Thus, it is reasonable to conclude that JYG is safe at the studied dosage levels and causes no acute or chronic toxicity in animal models. Electronic supplementary material The online version of this article (10.1186/s12906-018-2211-z) contains supplementary material, which is available to authorized users.

Endothelial cell (EC) activation and dysfunction have been linked to a wide variety of vascular inflammatory diseases. However, the role of microRNAs in EC activation and inflammation remains largely unknown. In this study, we found that miR-130b was significantly decreased in human umbilical vein endothelial cells (HUVECs) after lipopolysaccharides (LPS) treatment. Forced expression of miR-130b inhibited the LPS-induced activation of extracellular signal-regulated kinase (ERK) and the inflammatory genes expression, such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Furthermore, we identified that tumor progression locus 2 (Tpl2) is a direct target of miR-130b. Finally, in vivo overexpression of miR-130b via miR-130b agomir attenuates acute lung vascular inflammation in the LPS-induced sepsis mouse model. Taken together, our data demonstrated that miR-130b represses vascular inflammation via targeting Tpl2, suggesting that miR-130b mimics might be a promising therapeutic strategy for treatment of vascular inflammatory diseases.

Purpose C-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that is overexpressed in many cancers. CtBP1 transcriptionally represses a broad array of tumor suppressors, which promotes cancer cell proliferation, migration, invasion, and resistance to apoptosis. Recent studies have demonstrated that CtBP1 is a potential target for cancer therapy. This study was designed to screen for compounds that potentially target CtBP1. Methods Using a structure-based virtual screening for CtBP1 inhibitors, we found protocatechuic aldehyde (PA), a natural compound found in the root of a traditional Chinese herb, Salvia miltiorrhiza, that directly binds to CtBP1. Microscale thermophoresis assay was performed to determine whether PA and CtBP1 directly bind to each other. Further, clustered regularly interspaced short palindromic repeats associated Cas9 nuclease-mediated CtBP1 knockout in breast cancer cells was used to validate the CtBP1 targeting specificity of PA. Results Functional studies showed that PA repressed the proliferation and migration of breast cancer cells. Furthermore, PA elevated the expression of the downstream targets of CtBP1, p21 and E-cadherin, and decreased CtBP1 binding affinity for the promoter regions of p21 and E-cadherin in breast cancer cells. However, PA did not affect the expression of p21 and E-cadherin in the CtBP1 knockout breast cancer cells. In addition, the CtBP1 knockout breast cancer cells showed resistance to PA-induced repression of proliferation and migration. Conclusion Our findings demonstrated that PA directly bound to CtBP1 and inhibited the growth and migration of breast cancer cells through CtBP1 inhibition. Structural modifications of PA are further required to enhance its binding affinity and selectivity for CtBP1.

To investigate the levels of cytokines related to T-helper (Th) 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome (BHS) and blood-stasis syndrome (BSS). Sixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine (CM). Ten healthy subjects were considered as the control group. Cytokine levels of interleukin (IL)-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinase (MAPK) and STAT6 in the psoriatic lesions were determined using immunohistochemistry (IHC), Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively. Production of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group (P

Carboxyl-terminal–binding protein-1 (CtBP1) is a transcriptional corepressor with multiple in vitro targets, but its in vivo functions are largely unknown. We generated keratinocyte-specific CtBP1 transgenic mice with a keratin-5 promoter (K5.CtBP1) to probe the pathological roles of CtBP1. At transgene expression levels comparable to endogenous CtBP1 in acute skin wounds, the K5.CtBP1 epidermis displayed hyperproliferation, loss of E-cadherin, and failed terminal differentiation. Known CtBP1 target genes associated with these processes, e.g., p21 Brca1 , and E-cadherin, were downregulated in K5.CtBP1 skin. Surprisingly, K5.CtBP1 pups also exhibited a hair loss phenotype. We found that expression of the Distal-less 3 ( Dlx3 ), a critical regulator of hair follicle differentiation and cycling, was decreased in K5.CtBP1 mice. Molecular studies revealed that CtBP1 directly suppressed Dlx3 transcription. Consistently, K5.CtBP1 mice displayed abnormal hair follicles with decreased expression of Dlx3 downstream targets Gata3 Hoxc13 , and hair keratins . In summary, this CtBP1 transgenic model provides in vivo evidence for certain CtBP1 functions predicted from in vitro studies, reveals—to our knowledge—previously unreported functions and transcriptional activities of CtBP1 in the context of epithelial–mesenchymal interplay, and suggests that CtBP1 has a pathogenic role in hair follicle morphogenesis and differentiation.

Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), but it is unknown whether this loss increases UV-induced carcinogenesis, a major etiological factor in skin cancer. In the present study, mice with keratinocyte-specific Smad4 deletion (K14.Smad4(-/-)) and wild-type (WT) littermates were chronically UV-irradiated. Compared with WT, K14.Smad4(-/-) mice exhibited increased DNA damage and increased susceptibility to UV-induced skin cancer. Among genes involved in repairing UV-induced DNA damage, Excision repair cross-complementation group 1 (Ercc1) messenger RNA was significantly reduced in UV-treated K14.Smad4(-/-) skin compared with WT skin. Further analysis revealed that Smad4 loss confers reduced Snail binding to the Ercc1 regulatory elements, resulting in reduced Ercc1 transcription. Consistently, transient transfection of Snai1 into Smad4(-/-) keratinocytes led to increased repair of UV-induced DNA lesions. Transfection of Ercc1 into Smad4(-/-) keratinocytes restored repair of UV-induced DNA damage. Further, immunostaining revealed that the presence of Smad4 protein is associated with the presence of Snail and Ercc1 proteins in human skin SCC and precancerous actinic keratoses. Collectively, Smad4 loss-associated Snail reduction compromises Ercc1-mediated DNA repair, contributing to increased UV-induced skin carcinogenesis. Thus, we identified a role for Snail in UV-induced DNA repair.

Squamous cell carcinomas (SCCs) originate in stratified epithelia, with a small subset becoming metastatic. Epithelial stem cells are targets for driver mutations that give rise to SCCs, but it is unknown whether they contribute to oncogenic multipotency and metastasis. We developed a mouse model of SCC by targeting two frequent genetic mutations in human SCCs, oncogene Kras(G12D) activation and Smad4 deletion, to mouse keratin 15-expressing (K15+) stem cells. We show that transgenic mice developed multilineage tumors, including metastatic SCCs. Among cancer stem cell-enriched (CSC-enriched) populations, those with increased side population (SP) cells correlated with epithelial-mesenchymal transition (EMT) and lung metastasis. We show that microRNA-9 (miR-9) contributed to SP expansion and metastasis, and miR-9 inhibition reduced the number of SP cells and metastasis. Increased miR-9 was detected in metastatic human primary SCCs and SCC metastases, and miR-9-transduced human SCC cells exhibited increased invasion. We identified α-catenin as a predominant miR-9 target. Increased miR-9 in human SCC metastases correlated with α-catenin loss but not E-cadherin loss. Our results demonstrate that stem cells with Kras(G12D) activation and Smad4 depletion can produce tumors that are multipotent and susceptible to EMT and metastasis. Additionally, tumor initiation and metastatic properties of CSCs can be uncoupled, with miR-9 regulating the expansion of metastatic CSCs.

Acquired digital fibrokeratoma (ADFK) has typical characteristics and occurs most frequently on the fingers. The size of the tumor is usually less than 1 cm in diameter. We report a case of a typical ADFK, along with a review of the literature. A 76-year-old man presented with a two-year history of a slow-growing keratotic tumor on the edge aspect of his right hand ring finger. A literature search was conducted to identify published case reports of ADFK. Data on patient demographics, size and location of the lump, treatment, and follow-up were collected from each case report. This case is of interest because of the rarity of ADFK. Additionally, we have emphasized the importance of ruling out other causes of abnormal growths and considering fibrokeratoma during differential diagnoses.

Chronic skin ulcer (CSU), including diabetic ulcers, venous ulcers, radiation ulcers, and pressure ulcers, remains a great challenge in the clinic. CSU seriously affects the quality of life of patients and requires long-term dedicated care, causing immense socioeconomic costs. CSU can cause the loss of the integrity of large portions of the skin, even leading to morbidity and mortality. Chinese doctors have used traditional Chinese medicine (TCM) for the treatment of CSU for many years and have accumulated much experience in clinical practice by combining systemic regulation and tropical treatment of CSU. Here, we discuss the classification and pathogenic process of CSU and strategies of TCM for the intervention of CSU, according to the theories of TCM. Particularly, we describe the potential intervenient strategies of the “qing-hua-bu” protocol with dynamic and combinational TCM therapies for different syndromes of CSU.

TGFβ1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGFβ1 knockout mice reversed the dogma of TGFβ1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGFβ1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGFβ1. We developed K5.TGFβ1 mice with latent human TGFβ1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGFβ1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGFβ1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease. Our recent study reveals that treatments alleviating inflammatory skin phenotypes in this mouse model reduced Th17 cells, and antibodies against IL-17 also lessen the inflammatory phenotype. Examination of inflammatory cytokines/chemokines affected by TGFβ1 revealed predominantly Th1-, Th17-related cytokines in K5.TGFβ1 skin. However, the finding that K5.TGFβ1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGFβ signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs) by TGFβ1 reversely regulated by IL-6 highlights the dual role of TGFβ1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGFβ1 in inflammatory skin diseases.

To observe the clinical efficacy of Chinese medicine (CM) treatment of Hongyou Ointment and Shengji Powder on diabetic ulcers, and to observe the influence of CM treatment on the expressions of proteins associated with the Wnt signaling pathway, such as β-catenin, c-myc and K6.sixty-two patients fitting the registration standards were randomly divided into the CM group (31 patients) and the Western medicine (WM) group (31 patients) by a random number table. The patients in the CM group were treated with Hongyou Ointment and Shengji Powder externally. The patients in the WM group were treated with mupirocin ointment, growth factor (bFGF), and Vaseline gauze for external use and with basic therapies. Wound-healing time and four-week healing rate were recorded. The wounds were measured by digital photography and ImageJ software. Skin biopsies were obtained from 24 patients before CM treatment and 20 patients after CM treatment. Immunohistochemical tests and semi-quantitative imaging with NIH ImageJ 1.42 software were used to analyze the changes in protein expression of β-catenin, c-myc, and K6.Fifty-three patients completed the trial; four patients in the CM treatment group and five patients in the WM group dropped out. Among them, four were dissatisfied with the treatment process, two could not continue because of their jobs, two failed to complete the course of follow-up appointments, and one was diagnosed with squamous cell carcinoma during treatment. The comparison of ulcer healing rates between the two groups showed insignificant differences (P=0.77). The ulcer healing rates were 33.33% (9/27) in the CM group and 26.92% (7/26) in the WM group. However, the effective rate was significantly higher in the CM group (81.48%, 22/27) than in the WM group (57.69%, 15/26, P=0.04). The mean wound healing time was shorter in the CM group (22.71 ±5.46 days) than in the WM group (26.56 ±7.56 days, P=0.04). CM treatment was well tolerated, and there was no withdrawal due to adverse reactions. Immunohistochemical analysis in the refractory wound indicated higher expressions of β-catenin, c-myc and K6 compared with the normal skin. β-catenin was abnormally expressed in the nuclei of the keratinocytes and fibroblasts at the wound margins, and the expressions of c-myc and K6 were highly expressed in the full hyperplastic epidermis, especially in the granular layer (P0.05). The expressions of these proteins decreased after CM treatment. The expression levels of β-catenin, c-myc, and K6 proteins before and after the treatment were 101.88 ± 10.76 vs. 140.42 ±8.45; 113.27 ± 16.75 vs. 153.79 ±8.32; 90.39 ±11.07 vs. 151.29 ±7.39, respectively.CM treatment using Hongyou Ointment and Shengji Powder was efficient in the management of diabetic skin ulcers. The mechanism of action might be related to the inhibition of the Wnt signaling pathway.

There are many researches on the correlation between C-reactive protein (CRP) and prognosis of gastric cancer, but whether CRP could be used as an evaluation indicator for prognosis of gastric cancer patients, which was still controversial. Therefore, we conducted meta-analysis based on 18 studies involving 3656 objects. The results show that, CRP was significantly correlated with the risk of poor prognosis of gastric cancer patients [HR (95%CI) 1.50 (1.24, 1.81) P=0.000], and the risk of the poor prognosis can be significantly increased when CRP>10mg/L. In the different clinical stage, high expression of CRP can increases the risk of poor prognosis. The CRP can be used as an important indicator of poor prognosis of gastric cancer patients.

OBJECTIVE To explore the clinical efficacy of Qinzhu Liangxue Decoction (QZLXD), a compound traditional Chinese herbal medicine, in patients with blood-heat type psoriasis vulgaris. METHODS Fifty-eight patients diagnosed with blood-heat type psoriasis vulgaris were randomly divided into two groups: QZLXD group (30 cases) and ampeptide group (28 cases). Patients in both groups were treated for 4 weeks. Psoriasis Area and Severity Index (PASI) score, Dermatology Life Quality Index (DLQI) score and the level of serum vascular endothelial growth factor (VEGF) were obtained to evaluate the efficacy of the two treatments. RESULTS There was a better curative result in QZLXD group than in ampeptide group (P

Objective. To evaluate the effectiveness of external application of traditional Chinese medicine (EA-TCM) on venous ulcers.Methods. Seven databases were searched until April 2015 for randomized controlled trials (RCTs) of EA-TCM for venous ulcers. Risk of bias was assessed using Cochrane Handbook guidelines. Study outcomes were presented as risk ratios (RRs) for dichotomous data or mean differences (MDs) for continuous data.Results. Sixteen of 193 potentially relevant trials met the inclusion criteria; however, their methodological qualities were low. Comparison of the same intervention strategies revealed significant differences in total effectiveness rates between EA-TCM and conventional therapy groups (RR = 1.22, 95% confidence interval [CI] = 1.16–1.29, andP<0.00001). Compared to conventional therapy, EA-TCM combined with conventional therapy had a superior total effectiveness rate (RR = 1.11, 95% CI = 1.04–1.19, andP=0.003). There were no significant differences in recurrence rates during followup and final pain measurements between the experimental and those in the control groups (RR = 0.86, 95% CI = 0.31–2.39, andP=0.85; MD −0.75, 95% CI = −2.15–0.65, andP=0.29).Conclusion. The evidence that EA-TCM is an effective treatment for venous ulcers is encouraging, but not conclusive due to the low methodological quality of the RCTs. Therefore, more high-quality RCTs with larger sample sizes are required.

OBJECTIVE To study the effects of Shengji Huayu Recipe (a traditional Chinese medicine compound recipe for resolving stagnation and promoting granulation) and its decomposed formulas (Huayu Recipe for resolving stagnation and Shengji Recipe for promoting granulation) on the synthesis of collagen types I and III in granulation tissue of rats in early wound healing. METHODS Twenty-four male Sprague-Dawley (SD) rats with full-thickness skin lesion were randomized into 4 groups: Shengji Huayu Recipe-treated group, Shengji Recipe-treated group, Huayu Recipe-treated group and untreated group. Collagen types I and III in granulation tissue of the rats were tested with immunohistochemical methods and image analysis. RESULTS On the third day of wound healing, collagen I of the rats in both Shengji Huayu Recipe-treated group and Shengji Recipe-treated group was higher than that in the untreated group, and collagen I of the rats in Huayu Recipe-treated group was lower than that in the untreated group (P

Although Traditional Chinese medicine (TCM) is known to be effective for psoriasis patients, the responsible mechanisms still remain poorly understood. In this study, we aimed to evaluate the effect of one formula, named Jueyin granules (JYG) in the mouse model of the vaginal epithelium and tail epidermis. Additionally, we also determined the anti-inflammatory effects of JYG in an imiquimod- (IMQ-) induced psoriasis-like skin mouse model. Our results show that JYG can attenuate the IMQ-induced psoriasis-like inflammation, accompanied with increased epidermal hyperplasia. We also measured estrogenic stage mitosis of vaginal epithelial cells and the formation of granular cell layers in male mouse tails per 100 scales, as well as the tissue nitric oxide (NO) and malondialdehyde (MDA) levels using the ELISA method. The results suggest that JYG significantly inhibited mitosis in mouse vaginal epithelial cells, promoted the formation of the squamous epidermal granular layer in mice tails, and reduced the levels of NO and MDA in an imiquimod-induced psoriasis-like skin mouse model after 14 d (P<0.05). These results demonstrate that JYG might be an effective clinical treatment for psoriasis and the effects may be related to inhibited keratinocytes proliferation, improved parakeratotic epidermal cells, and reduced expression of NO and MDA.

We report that K5.Smad7 mice, which express a Smad7 transgene under the control of a keratin 5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to nuclear factor κB (NF-κB) activation, which is known to contribute to oral mucositis, we found activated transforming growth factor β (TGF-β) signaling in cells from this condition. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-β signaling Smads and their co-repressor C-terminal binding protein 1 (CtBP1) transcriptionally repressed Rac1, and that Smad7 abrogated this repression. Knocking down Rac1 expression in mouse keratinocytes abrogated Smad7-induced migration. Topical application of Smad7 protein conjugated with a cell-permeable Tat tag to oral mucosa showed prophylactic and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified new molecular mechanisms involved in oral mucositis pathogenesis, and our data suggest an alternative therapeutic strategy to block multiple pathological processes in this condition.

Objective To observe the clinical effect of escin on patients with cutaneous pruritus caused by blood stasis and wind-dryness and to prove the theory that "wind should be treated by regulating blood disorder, and wind disappears after activating blood" in traditional Chinese medicine (TCM). Methods Fifty-one patients were randomly divided into escin-treated group (n=30) and loratadine-treated group (n=21). The patients in the escin-treated group were treated with escin for 4 weeks (300 mg, b.i.d.), and the patients in the loratadine-treated group were treated with loratadine (10 mg, q.d.). Symptom score reducing index (SSRI) was used to assess the pruritus degree, lesion range and lesion shape before the treatment, 2 weeks and 4 weeks after the treatment, respectively. Results Two weeks after the treatment, the effective rate of the escin-treated group was 63.3%, and the effective rate of the loratadine-treated group was 67.0%. Four weeks after the treatment, the effective rates were 86.7% and 80.0% in escin- and loratadine-treated groups respectively. There was no statistical difference in total scores of SSRI in two groups (P>0.05), and the scores of pruritus degree and lesion shape also had no statistical difference (P>0.05), while the score of lesion range of the escin-treated group was lower than that of the loratadine-treated group (P Conclusion Escin has satisfactory effect in treating pruritus caused by blood stasis and wind-dryness. The study confirms the TCM theory that "wind should be treated by regulating blood disorder, and wind disappears after activating blood".