Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis.

Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

Efficacy and action mechanisms of a Chinese herbal formula on experimental models of atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a skin inflammatory disease characterized by erythema, eruption, lichenification and pruritus. Shi Zhen Formula (SZF), an empirical Chinese herbal preparation, has clinical efficacy in relieving the symptoms of AD patients. However, the underlying molecular mechanisms of SZF remained unclear. AIM OF THE STUDY: We aimed to investigate the anti-AD effects of SZF and elucidate its underlying molecular mechanisms using in vitro and in vivo models of AD. MATERIALS AND METHODS: High-performance liquid chromatography analysis was performed for quality control of SZF extract. The anti-inflammatory effect of SZF was investigated through evaluating the levels of nitric oxide (NO), chemokines and pro-inflammatory cytokines in the lipopolysaccharide (LPS) stimulated RAW264.7 cells. AD-like skin lesions in female BALB/c mice were induced by 2,4-dinitrochlorobenzene (DNCB). SZF (3.15, 6.30 and 9.45 g/kg) and dexamethasone (5 mg/kg) were administered by gavage daily for 15 consecutive days. The body weight, skin thickness, skin dermatitis severity and scratching behaviors were recorded throughout the study. Histological analysis, reverse transcription-quantitative polymerase chain reaction (RT-PCR), western blot (WB) and ELISA analysis were used to illuminate the molecular targets associated with the anti-AD effects of SZF. RESULTS: SZF markedly decreased the epidermal thickening and infiltration of mast cells in the ears and dorsal skin of the 2,4-dinitrochlorobenzene (DNCB)-treated mice. SZF not only suppressed the levels of immunoglobulin E (IgE), histamine, thymic stromal lymphopoietin (TSLP) and IL-4 in the serum but also suppressed the over-production of IL-4 and IL-6 and gene expressions of IL-4, IL-13, IL-31 and TSLP in the dorsal skin. Moreover, SZF improved epidermal barrier by increasing the protein expressions of filaggrin, involucrin and loricrin and inhibited the activation of NF-κB p65 pathway in the dorsal skin of the DNCB-treated mice. CONCLUSION: SZF alleviates DNCB induced AD-like skin lesions in mice through regulating Th1/Th2 balance, improving epidermal barrier and inhibiting skin inflammation. Our research findings provide scientific footing on the use of this Chinese herbal formula for the treatment of AD.

Effects of Allium sativum on IFN-γ and IL4 concentrations in mice with cystic echinococcosis.

The aim of the current investigation was to assess the impacts of methanolic extract of Allium sativum (MEAS) on IL-4 (a cytokine derived from Th2 cells) and IFN-É£ (a cytokine derived from Th1 cells) levels in mice infected with Echinococcus granulosus. Sixty healthy BALB/c female mice were used in this study. Each animal was intraperitoneally injected with 1500 protoscoleces. The infected animals were randomly divided into six groups: albendazole (100 mg/kg), MEAS 10 (10 mg/kg), MEAS 20 (20 mg/kg), MEAS 40 (40 mg/kg), MEAS 80 (80 mg/kg) and control group with no treatment. The studied animals received albendazole and/or MEAS through drinking water for 30 days. Serum IFN-γ concentration significantly increased in the MEAS 20 and 80 groups in comparison to the control, albendazole and MEAS 10 groups (P < 0.05). The serum IL-4 level showed no significant difference between the trial groups. The findings of this study showed that MEAS at 20 and 80 mg/kg concentrations enhanced Th1 cell response in mice with cystic echinococcosis.

Clinical Efficacy of Vitamin D3 Adjuvant Therapy in Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND: Vitamin D supplementation has been proven to be effective in the treatment of allergic rhinitis (AR). OBJECTIVE: We conducted the present study to explore the role and efficacy of vitamin D adjuvant therapy for the treatment of inflammation in patients with AR. METHODS: Out of 127 patients with potential eligible AR, 60 were randomly assigned into two groups and were finally included in our analysis (n=30 for each intervention). The patients with potential eligible AR were randomly allocated to intervention with desloratadine citrate disodium (DCD, 8.8 mg/day) without and with vitamin D3 nasal drops (1.5х106 IU, once/week) for four weeks. Thirty healthy control subjects were included in our study. We assessed the changes in the serum 25(OH)D, peripheral blood eosinophils, interleukin (IL)-4 levels, and nasal symptoms. Serum 25(OH)D, peripheral blood eosinophils, and IL-4 levels were detected respectively with liquid chromatography-tandem mass spectrometry (LC-MS/MS), a blood detector, and enzyme-linked immunosorbent assay. RESULTS: Our patients who received vitamin D3 adjuvant therapy had a higher serum 25(OH)D level (47.57 ± 2.83 vs. 31.51 ± 2.95 ng/ml, p=0.000) and lower AR symptoms score (2.07 ± 1.89 vs. 3.37 ± 1.50, p=0.005), serum IL-4 (10.38 ± 3.41 vs. 12.79 ± 5.40 pg/ml, p=0.043), and peripheral blood eosinophils (0.34 ± 0.09 vs. 0.41 ± 0.10 109/l, p=0.003) compared with DCD single treatment. The efficacy rates of DCD with and without vitamin D3 in AR were 97% and 84%, respectively. CONCLUSION: Nasal vitamin D3 combined with DCD could improve the clinical symptoms of AR. Vitamin D3 adjunct therapy showed significant effects on inhibiting inflammation in patients with AR. We concluded that vitamin D3 supplementation could be an effective adjuvant therapy in AR patients.

Efficacy of Yiqigubiao pill on chronic obstructive pulmonary disease in rats with the disease induced by lipopolysaccharide and cigarette-smoke fumigation.

OBJECTIVE: To investigate the efficacy of Yiqigubiao pill (YQGB) on chronic obstructive pulmonary disease (COPD) in rats with the COPD induced by lipopolysaccharide (LPS) and cigarette- smoke fumigation. METHODS: In this study, six groups of rats were set up, including control group, model group, positive control group (aminophylline) and YQGB (high, medium and low doses) groups. Tracheal injection of lipopolysaccharide (LPS) and cigarette-smoke fumigation induced COPD in rats. The general condition, incubation period and coughing times, lung function, level of inflammatory factors, leukocyte condition and pathological changes of bronchus and lung tissue were observed in rats of each group. RESULTS: In the COPD rats, the latent period of coughing was shortened and the cough frequency was increased significantly; the pulmonary function was significantly decreased, which was manifested by the increased lung tissue resistance and respiratory system resistance, and the decreasing percentage of forced expiratory volume and forced expiratory volume in the 0.3 s (FEV0.3/FVC); the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-4 in serum were obviously increased, and the NEUT% in bronchoalveolar lavage fluid was significantly increase. YQGB could obviously prolong the latent period of cough, and reduce the cough frequency and the content of TNF-α in serum. YQGB can also significantly reduce respiratory resistance and increase FEV0.3/FVC value. The results of histopathology showed that YQGB significantly reduced the pathological changes of tracheal mucosa and lung caused by COPD. YQGB obviously increased level of AQP1, which was down-regulated in the COPD rats. CONCLUSION: YQGB could significantly improve the pulmonary function, reduce inflammation and alleviate lung and bronchial diseases in the COPD rats.

Serum and milk concentrations of oxidant and anti-oxidant markers in dairy cows affected with bloody milk.

This study was conducted to determine the serum and milk levels of thiobarbturic acid-reac- tive substances (TBARS), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxi- dase (GSH-Px), vitamin E and selenium, IL-4 and IL-6 in lactating dairy cows affected with bloody milk using commercially available ELISA kits. Milk and whole blood samples were collected from 60 cows affected with bloody milk and 20 apparently healthy cows for control. In the serum, levels of GSH-Px and SOD were significantly (p˂0.05) higher in healthy cows compared to cows affected with bloody milk while the levels of TBARS and NO were significantly (p˂0.05) higher in affected cows. In the milk, levels of SOD, TBARS and NO were significantly (p˂0.05) higher in affected cows. In the serum, levels of vitamin E were significantly (p˂0.05) lower in affected cows compared to healthy cows, while no significant changes were observed in the levels of this vitamin in the milk between healthy and affected cows. In the serum, levels of selenium were significantly (p˂0.05) lower in affected cows while in milk, selenium levels were significantly (p˂0.05) higher in affected cows compared to healthy ones. Levels of IL-4 were significantly (p˂0.05) lower in the serum and milk of affected cows compared to healthy cows while levels of IL-6 were significantly (p˂0.05) higher in both serum and milk of affected cows. Results of this study suggest a possible role of oxidative stress in the pathogenesis of bloody milk in dairy cows.

Alpinetin prevents inflammatory responses in OVA-induced allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways in mice.

Allergic asthma is the most common type of asthma which characterized by inflammatory responses of the airways. Alpinetin, a flavonoid compound derived from the ginger family of medicinal herbs, possesses various biological properties including anti-inflammatory, anti-oxidant and other medical effects. In this study, we aimed to evaluate the effects of alpinetin on OVA-induced allergic asthma, and further to examine its molecular mechanisms underlying these processes in vivo and in vitro. Mice were sensitized and challenged with OVA to build allergic asthma model in vivo. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells analysis and lung tissues were examined for histopathological examination. The levels of IL-5, IL-13, IL-4, IgE, TNF-α, IL-6 and IL-1ß were determined by the respective ELISA kits. The PI3K/AKT/NF-κB and HO-1 signaling pathways were examined by western blot analysis. The results showed that alpinetin significantly ameliorated OVA-induced pathologic changes of lungs, such as decreasing massive inflammatory cell infiltration and mucus hypersecretion, and reduced the number of inflammatory cells in BALF. Alpinetin also decreased the OVA-induced levels of IL-4, IL-5, IL-13 and IgE. Furthermore, alpinetin inhibited OVA-induced phosphorylation of p65, IκB, PI3K and AKT, and the activity of HO-1 in vivo. More importantly, these anti-inflammatory effects and molecular mechanisms of alpinetin has also been confirmed in LPS-stimulated RAW 264.7 macrophages in vitro. In conclusion, above results indicate that alpinetin exhibites a potent anti-inflammatory activity in allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways, which would be used as a promising therapy agent for allergic asthma.

The efficacy and safety of Chinese herbal compound or combined with western medicine for pediatric adenoidal hypertrophy: A protocol for systematic review and meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) or combined with western medicine in the treatment of pediatric adenoidal hypertrophy has been widely used in clinical practice, but the overall efficacy and safety is still unclear. This paper aims to evaluate the efficacy and safety analysis of TCM or combined with western medicine for pediatric adenoidal hypertrophy. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) were searched for randomized controlled trials of TCM or combined with western medicine for pediatric adenoidal hypertrophy from the date of establishment to July 2020, and Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform (ICTRP), and Chinese Clinical Trials Registry (ChiCTR) were searched for unpublished grey literature. Two researchers independently applied RevMan 5.3 software for data extraction and risk assessment of bias. RESULTS: The effectiveness and safety of TCM or combined with western medicine for pediatric adenoidal hypertrophy is evaluated by means of the Adenoid (A) /(Nasopharyngeal (N) ratio, clinical efficacy, integral score of TCM syndromes, clinical single symptom score, disease specific quality of life for children with obstructive sleep apnea 18 items survey (OSA-18), Interleukin 4 (IL-4) and adverse reaction incidence. CONCLUSION: This study will provide theoretical support for the clinical application of TCM or combined with western medicine for pediatric adenoidal hypertrophy. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/J76AG.

Interferon gamma/interleukin-4 modulation, anti-inflammatory and antioxidant effects of hesperidin in complete Freund's adjuvant (CFA)-induced arthritis model of rats.

BACKGROUND: This study sought to assess the effect of hesperidin on serum inflammatory cytokines and oxidative damage in liver of complete Freund's adjuvant (CFA)-induced arthritic rats. METHOD: Fifty-six adult female Wistar rats (220-250 g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14th day prior to oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days. RESULT: The result showed that treatment with both doses of hesperidin and dexamethasone in the joint of arthritic rats significantly (p < .05) diminished paw swelling/edema and arthritis score as well as enhanced latency in thermal hyperalgesia test. In addition, hesperidin treatment in arthritis rats showed significant (p < .01) improvement in red blood cells and platelets counts as well as hemoglobin and hematocrit compared to the arthritis control rat group. Furthermore, hesperidin treatment significantly (p < .05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < .05) decreased the liver of thiobarbituric acid reactive species and reactive oxygen species levels but raised the levels of total and non-protein thiols of rat induced with CFA. The reduced activities of liver δ-aminolevulinate dehydratase, catalase, glutathione-S transferase in arthritic rats were significantly (p < .05) increased with hesperidin treatment in arthritic rats. This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of serum IFN-γ and IL-4 levels as well as protection against oxidative damage. CONCLUSION: Hence, hesperidin could be a potential immune-modulatory, anti-inflammatory and anti-oxidant agent.

Effect of nose sensitive pill (NSP) on serum IFN-γ and il-4 levels in allergic rhinitis using rats model.

This study was conducted to investigate the changes of serum interleukin-4 (IL-4), interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) in allergic rhinitis model rats after using the traditional Chinese nose sensitive pill (NSP) and its possible mechanism to treat allergic rhinitis. Forty Sprague Dawley (SD) rats were randomly divided into 4 groups of 10 rats each i.e. blank control group, model group, nose sensitive pill group and loratadine group. Allergic rhinitis was induced in all three groups (except blank control group) using ovalbumin as allergen. After successful induction of allergic rhinitis, intragastric administration of 0.9% NaCl solution, NSP or loratadine solution was carried-out, respectively. The behavior of rats was observed before administration and then after 1, 3 and 5 weeks. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of 4 cytokines in each group after 5 weeks. After 5 weeks study period, nasal symptoms of NSP group and loratadine group were significantly (P<0.01) lower than those of model group. Compared with blank control group, levels of IL-4 and IL-17 in model group increased, and levels of IFN-γ and IL-10 decreased significantly (P<0.01). Compared with model group, levels of IFN-γ and IL-10 increased but levels of IL-4 and IL-17 decreased significantly (P<0.01) in NSP and loratadine group. On the basis of findings of this study, NSP is an effective prescription to treat allergic rhinitis. One of its therapeutic mechanisms is to regulate balance between Th1/Th2 and Th17/Treg cells by influencing the levels of IL-4, IFN-γ, IL-17 and IL-10.

Chamaejasmine Isolated from Wikstroemia dolichantha Diels Suppresses 2,4-Dinitrofluoro-benzene-Induced Atopic Dermatitis in SKH-1 Hairless Mice.

Plants of the genus Wikstroemia have long been used as traditional medicines to treat diseases like pneumonia, rheumatism, and bronchitis. This study was designed to determine the effect of chamaejasmine, a biflavonoid present in W. dolichantha, on atopic dermatitis (AD)-like skin lesions in a 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD. Initially, we examined the anti-allergic activities of ten flavonoids from W. dolichantha by measuring ß-hexosaminidase release from RBL-2H3 cells. Subsequently, an SKH-1 hairless mouse model of AD was developed based on the topical application of DNCB. Chamaejasmine (0.5%) or pimecrolimus (1%, positive control) were applied to dorsal skins of DNCB-sensitized AD mice for two weeks. Serum IL-4 and IgE levels were determined using enzyme-linked immunosorbent assay kits and transepidermal water loss (TEWL) and skin hydration were measured using a Tewameter TM210 and a SKIN-O-MAT, respectively. Of the ten flavonoids isolated from W. dolichantha, chamaejasmine most potently inhibited DNP-specific IgE-induced degranulation in RBL-2H3 cells. Topical administration of chamaejasmine attenuated the clinical symptoms of DNCB-induced dermatitis (i.e., itching, dryness, erythema, and edema). Histological analyses demonstrated that dermal thickness and mast cell infiltration in dermis were significantly reduced by chamaejasmine. In addition, 0.5% chamaejasmine inhibited DNCB-induced increases in total IL-4 and IgE levels in serum, improved skin barrier function, and increased epidermis moisture. Our findings suggest chamaejasmine might be an effective therapeutic agent for the treatment of atopic diseases.

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia.

Functional dyspepsia (FD) is one of the most prevalent functional gastrointestinal disorders, and more and more multicomponent drugs represented by traditional Chinese medicines have provided a favorable therapeutic effect in its treatment. However, their precise localization in the clinic, as well as corresponding mechanism, is ambiguous, thus hindering their widespread use. To meet this requirement, a precise and systematic approach based on a restriction of special disease-related molecules and the following network pharmacology analysis was developed and applied to a multicomponent conventional drug, XiaoErFuPi (XEFP) granules. Experimental verification of the results indicates that this approach can facilitate the prediction, and the precise and systematic efficacy of XEFP could be easily revealed, which shows that XEFP has an advantage over the positive control drug on lactate, gastrin, interleukin 4 and calcitonin gene-related peptide. Moreover, by the proteomics analysis, its superposition of multi-target effects was revealed and a new candidate target for the treatment of FD, striatin, was obtained and verified. This study provides a practicable precise approach for the investigation of the efficacy of multicomponent drugs against FD and offers a promising alternative for the systematical management of FD.

Protective efficacy induced by DNA prime and recombinant protein boost vaccination with Toxoplasma gondii GRA14 in mice.

Toxoplasma gondii, the etiological agent of toxoplasmosis, can cause severe or lethal damages in both animals and man. So, tends to develop a more effective vaccine to prevent this disease is extremely needed and would be so prominent. The novel dense granule antigen 14 (GRA14) has been identified as a potential vaccine candidate against T. gondii infection. The aim of this study was evaluation of protective immunity induced by prime/boost vaccination strategy of GRA14 antigen with calcium phosphate (CaPNs) or Aluminum hydroxide (Alum) nano-adjuvants in BALB/c mice. The finding showed that immunization with the prime-boost strategy using plasmid DNA (pcGRA14) and recombinant protein (rGRA14) with nano-adjuvants significantly elicited levels of specific IgG antibodies and cytokines against T. gondii infection. Given that, there were the high levels of total IgG, IgG2a, IFN-γ in mice of rGRA14-CaPNs and pcGRA14 + rGRA14-CaPNs groups, which indicating a Th-1 type response. While immunization of mice with Alum based rGRA14 and pcGRA14 + rGRA14 elicited specific IgG1 and IL-4 levels, which was confirmed a Th-2 type response. Mice immunized with DNA prime-protein boost vaccine with nano-adjuvants produce more vigorous specific lymphoproliferative responses than mice immunized with other antigen formulations. In addition, the CaPNs-based prime-boost vaccine of pcGRA14 + rGRA14 showed the longest survival time in mice and the lowest parasitic load in their brain tissue compared to the other groups. The results obtained in this study show that the use of GRA14 based DNA prime-protein boost vaccination regime with CaPNs can dramatically enhanced both humoral and cellular immune responses. Therefore, this strategy can provide a promising approach to the development of an effective vaccine against T. gondii infection in the future.

Modification of HIF-1α, NF-aκB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated with hyperbaric oxygen.

Introduction: Diabetic foot ulcers are a frequent complication of diabetes and the first cause of non-traumatic lower limb amputation. They affect quality of life, restrict social productivity and generate a high economic burden for health care systems. Hyperbaric oxygen (HBO2) therapy is an adjunctive treatment option because it improves wound healing in the short term. However, its ability to modulate the pro- and anti-inflammatory balance and the hypoxic cell response in the clinical setting has not been fully described. Objective: To determine modifications in HIF-1α, NF-κB, IGFBP-3, and VEGF expression in wounds as well as circulating inflammatory cytokines in patients with diabetic foot ulcers subjected to HBO2. Materials and methods: We studied 17 ambulatory patients and one hospitalized patient with diabetic foot ulcers classified as Grade 3 or 4 according to the Wagner scale. All underwent HBO2 therapy. Tissue expression of HIF-1α, NF-κB, IGFBP-3, and VEGF was determined by immunohistochemistry. Plasma levels of adiponectin, IL-6, IFN-γ, IL-10 and IL-4 were measured by ELISA and chemiluminescence. Fibrosis and angiogenesis were determined by Masson's trichrome staining. Results: Ulcers in all patients healed after one month of HBO2, and none presented relapses at the one-year follow-up. At the beginning of treatment, HIF-1α and NF-κB expression was observed mainly in the nucleus, whereas these proteins were localized in the cytoplasm at the end of HBO2. There were significant modifications in VEGF expression after therapy, an increase in the plasma level of proinflammatory IL-6, and a decrease in that of IFN-γ. IGFBP-3 expression and plasma levels of adiponectin were increased at the end of HBO2. Increases in fibrosis and angiogenesis were also observed. Conclusion: These results suggest that adjuvant HBO2 modifies the proinflammatory balance related to the cellular response to hypoxia.

Effect of Topically Applied Wikstroemia dolichantha Diels on the Development of Atopic Dermatitis-Like Skin Symptoms in Mice.

Plants of the genus Wikstroemia are traditionally used to treat inflammatory diseases like bronchitis and rheumatoid arthritis. In the present study, the anti-atopic effects of an EtOH extract of Wikstroemia dolichantha (WDE) on oxazolone- and DNCB (2,4-dinitrochlorobenzene)-induced dermatitis in mice were investigated. Both ears of BALB/c mice were exposed to oxazolone, and dorsal skins of SKH-1 hairless mice were sensitized with DNCB to induce acute eczematous atopic skin lesions. 1% WDE was applied daily to oxazolone- and DNCB-induced AD mice for two or three weeks, respectively. Total IL-4 and IgE concentrations in serum, transepidermal water loss (TEWL) and skin hydration were assessed. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to determine the composition of WDE. Dermal application of 1% WDE grossly and histopathologically improved oxazolone- and DNCB-induced AD skin symptoms. Epidermal thickness and mast cell infiltration were significantly lower in animals treated with WDE than in vehicle controls. Furthermore, in addition to reducing DNCB-induced increases in serum IL-4 (interleukin 4) and IgE (immunoglobulin E) levels, WDE also decreased TEWL and increased skin hydration (indicative of improved skin barrier function). The four flavonoids taxifolin, aromadendrin, padmatin and chamaejasmine were tentatively identified in WDE by HPLC-DAD/QTOF-MS. The above results show WDE protected against oxazolone- and DNCB-induced AD in mice by down-regulating the TH2-associated cytokine IL-4 and improving skin barrier function and suggest WDE might be useful for the management of atopic dermatitis.

Zhixiong Capsule (ZXC), a traditional Chinese patent medicine, prevents atherosclerotic plaque formation in rabbit carotid artery and the related mechanism investigation based on network pharmacology and biological research.

BACKGROUND AND AIMS: Chinese patent medicine Zhixiong Capsule (ZXC) has been used in clinical treatment against blood stasis-induced dizziness and headache for many years in China. HYPOTHESIS/PURPOSE: Recent clinical observations demonstrated a good efficacy of ZXC against atherosclerotic plaque formation in carotid arteries. The aims of this study were to verify the plaque-preventing efficacy of ZXC in animals and to investigate the underlying mechanisms. STUDY DESIGN/METHODS: ZXC (185 mg/kg and 370 mg/kg) was administrated to rabbits which received collar implantation accompanied with high fat diet administration (12 days). The blood-dissolved components of ZXC were identified by an UPLC-QTOF-MS method. The key components and targets of ZXC were then predicted based on network pharmacology analysis and biological investigations. RESULTS: Compared with vehicle control group, ZXC administration (185 mg/kg) significantly prevented plaque formation and attenuated intima thickening in the collar-implanted carotid arteries, markedly decreased blood lipid level, and increased plasma IL-4 level in rabbits. A total of 23 blood-dissolved components were identified. Four ingredients (namely, kaempferol, daidzein, puerarin, miltirone) along with leech, and three targets (namely, JUN, FOS and TP53) were recognized to play important roles for ZXC bioactivity. CONCLUSION: It could be concluded that ZXC could be applied to prevent atherosclerotic plaque formation and intimal thickening in carotid arteries at the current clinical dose.

Yan-Hou-Qing formula attenuates allergic airway inflammation via up-regulation of Treg and suppressing Th2 responses in Ovalbumin-induced asthmatic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Yan-Hou-Qing (YHQ), a Chinese medicine formula containing fourteen kinds of materials, has been designed for pharyngitis and cough treatment in Oriental medicine. In the present study, the anti-allergic effects and underlying mechanisms of YHQ in inhibition of airway hyper responsiveness (AHR) was explored in an ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: BALB/c mice were sensitized by OVA and cholera toxin (CT) and challenged with OVA intranasally to induce allergic asthma mouse model. YHQ (200 mg/kg) was orally administered for 3 weeks from week-2 after OVA sensitization. The AHR and histological changes of lung tissues were evaluated by whole-body barometric plethysmography analysis and hematoxylin and eosin (H&E) staining, respectively. The serum concentration of OVA-specific IgE and T helper 2 (Th2) cytokines (IL-4 and IL-13) were determined by enzyme-linked immune sorbent assay (ELISA). Flow cytometry was performed to evaluate the percentage of CD4+CD25+Foxp3+ regulatory T cells (Treg) in the spleen. RESULTS: The elevated AHR responses, heavier inflammatory cell infiltration and Th2 cytokines in allergic asthma group indicated Ovalbumin-induced asthmatic mouse models were built successfully. Compared to allergic asthma group, OVA-induced AHR responses and eosinophil infiltration in lung were improved significantly, and the productions of OVA-specific IgE and Th2 cytokines, IL-4 and IL-13, in the serum were also reduced dramatically after the treatment of YHQ. Moreover, YHQ treatment significantly increased the percentage of CD4+CD25+Foxp3+ Treg in OVA-induced allergic asthma mouse model. CONCLUSIONS: YHQ improves the allergic asthma related symptoms via promotion of CD4+CD25+Foxp3+ Treg and suppression of Th2 responses in mouse model, suggesting YHQ can be used as a potent agent to alleviate allergic asthma related symptoms.

Effect of chiropractic manipulation on disrupted epithelium barrier and its mechanism of specialized pro-resolving mediators in a spleen-deficiency murine model.

OBJECTIVE: To investigate the influence of spleen deficiency on the epithelial barrier of jejunum and lungs in a rat model of spleen-deficiency and the effect and potential specialized pro-resolving mediators (SPMs) mechanism of chiropractic manipulation. METHODS: Three-week-old male Sprague-Dawley rats were divided randomly into normal control group (n = 6), spleen-deficiency group (n = 5) and chiropractic group (n = 6). Spleen-deficiency model was induced in spleen-deficiency group and chiropractic group. Moreover, chiropractic manipulation was performed in chiropractic group. Four weeks later, systemic Th1/Th2 balance was evaluated by the ratio of plasma interferon (IFN)-γ/interleukin (IL)-4 levels by enzyme-linked immunosorbent assay (ELISA). Epithelial barrier integrity were assessed by the observation of morphological changes by hematoxylin-eosin staining and zonula occludens (ZO)-1 gene expressions by quantitative real time polymerase chain reaction in jejunum and lungs. Plasma resolvin D1 (RvD1) and lipoxin A4 (LXA4) levels were measures by ELISA for endogenous SPMs production. The levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in jejunum and lungs were also measured by HPLC-MS/MS. RESULTS: Comparing with normal control group, spleen-deficiency group showed disrupted mucosa in jejunum, inflammatory condition in lungs, significantly decreased ratio of plasma IFN-γ/IL-4 levels and lower expressions of ZO-1 mRNA in both jejunum and lung tissues. Comparing with spleen-deficiency group, chiropractic group had less disrupted mucosa in jejunum and inflammatory condition in lungs, significantly increased systemic ratio of IFN-γ/IL-4 and expressions of ZO-1 mRNA in both jejunum and lung tissues. Chiropractic group had significantly enhanced plasma levels of RvD1 and LXA4, but had no significantly higher levels of DHA and AA in jejunum and lungs when comparing with spleen-deficiency group. CONCLUSION: Spleen deficiency caused systemic Th1/Th2 imbalance towards Th2 polarization and epithelial barrier disruption in jejunum and lungs. Chiropractic manipulation helped enhance endogenous SPMs production, which might be one of the action mechanism of chiropractic manipulation on the improvement of epithelial barrier disruption.

Effect of Combined Acupuncture Anesthesia on Surgical Dosage and Serum IL-4, IL-10 of Pneumonectomy Patients.

OBJECTIVE: To analyse the effects of combined acupuncture anesthesia on surgical dosage and serum interleukin-4 (IL-4), interleukin-10 (IL-10) of pneumonectomy patients. STUDY DESIGN: A randomised controlled trial (RCT). PLACE AND DURATION OF STUDY: Lanzhou University Second Hospital, Lanzhou, China, from January 2016 to November 2017. METHODOLOGY: A total of 110 patients undergoing pneumonectomy were randomly divided into group A and group B, with 55 cases in each group. Group A was treated with combined 2Hz acupuncture anesthesia, while group B was treated with combined 2Hz/100Hz acupuncture anesthesia. The additional propofol, fentanyl dosage, and changes in heart rate and systolic blood pressure 5 min before and during extubation were compared between the two groups. The serum IL-4 and IL-10 levels were measured 10 minutes after skin incision and 24 hours after surgery using ELISA. Pain was rated by visual analogue scale (VAS) at 24 hours after surgery. RESULTS: There was no statistically significant difference between group A and group B in the intraoperative additional propofol and fentanyl dosags (p=0.541 and 0.719, respectively). There is no statistical difference in heart rate and systolic blood pressure between group A and group B at 5 minutes before and during extubation (p=0.151, 0.660 and 0.734, 0.528, respectively). There is no statistical difference between group A and group B in serum IL-4 and IL-10 levels 10 minutes after surgical incision (p=0.916 and 0.841, respectively). However, serum IL-4 and IL-2 levels in group A are statistically lower than that of group B at 24 hours after surgery (all p<0.001). The VAS score at 24 hours after surgery in group A was 2.44 ±0.71 points, which was significantly lower than that of group B (3.82 ±0.77 points, p<0.001). CONCLUSION: Combined 2 Hz, 2 Hz/100 Hz acupuncture anesthesia need few anesthetic dosages of propofol and fentanyl to stabilise the patient's blood pressure and heart rate when intubated under general anesthesia; but combined 2 Hz acupuncture anesthesia can reduce IL-4 and IL-10 levels during surgery stress to a greater extent than the latter, and can effectively lower patients' serum IL-4, IL-10 expression after surgery.

Treatment mechanism of tolerogenic dendritic cells on rheumatoid arthritis.

This study aims to explore the possible mechanism of treatment of collagen-induced rheumatoid arthritis (RA) by tolerogenic dendritic cells (tDCs). Different methods were used to induce and cultivate tDCs, and suitable conditions for tDC cultivation were explored. The experimental RA induced by collagen in mouse was treated by the obtained tDCs, and the possible mechanism was explored. The serum concentration of TNF-α, IFN-ß, IL-4 and anti-type II collagen antibody were detected by ELISA. The anti-type II collagen antibody of mice without treatment was higher than that without disease onset, while the Blank-DC group, VIP-DC group and Bay-D had no statistically significant differences (P>0.05). Compared to the group without disease onset, the TNF-α level of those without treatment was significantly higher, while INF-γ, IL-1ß and IL-4 concentration showed no significant difference (P>0.05). Compared to the untreated group, the TNF-α and IL-1ß concentration after VIP-DC treatment were significantly decreased, while IL-4 was increased (P less than0.05). In summary, VIP-DC and Bay-DC alleviate joint inflammation, synovitis and bone erosion by reducing the production of anti-type II collagen antibody, inhibiting proinflammatory factors and increasing inflammation inhibitors.