A multi-target protective effect of Danggui-Shaoyao-San on the vascular endothelium of atherosclerotic mice.

BACKGROUND: Atherosclerosis (AS) is a chronic disease characterized by abnormal blood lipid metabolism, inflammation and vascular endothelial injury. Vascular endothelial injury is the initial stage during the occurrence of AS. However, the function and mechanism of anti-AS are not well characterized. Danggui-Shaoyao-San (DGSY) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of gynecological diseases, and has been widely used in the treatment of AS in recent years. METHODS: ApoE-/- atherosclerosis male mice were established by feeding with high-fat diet, and then randomly divided into three groups: Atherosclerosis group (AS), Danggui-Shaoyao-San group (DGSY), and Atorvastatin calcium group (X). The mice were administered with the drugs for 16 weeks. Pathological changes in aortic vessels were examined by staining with Oil red O, Masson and hematoxylin-eosin. In addition, blood lipids were analyzed. The level of IL-6 and IL-8 in aortic vessels were detected by ELISA and the expression of ICAM-1 and VCAM-1 in the aortic vascular endothelium were measured by Immunohistochemical. The mRNA expression of interα5ß1/c-Abl/YAP in the aortic vessels were measured by Real-time quantitative PCR and location of expression was assessed by immunofluorescence. RESULTS: DGSY can significantly reduce the content of TC,TG and LDL-C and increase the level of HDL-C in the serum, reduce the plaque area and inhibit the concentration of IL-6 and IL-8, down-regulate the expression of IVAM-1,VCAM-1 and interα5ß1/ c-Abl/YAP in the aortic vessels. CONCLUSIONS: Collectively, DGSY can alleviate vascular endothelium damage and delay the occurrence of AS, and the underlying mechanism may be related to the multi-target protective of DGSY.

Yiqi Jiedu herbal decoction attenuates the 2 Gy 60Co γ ray induced spleen injury by inhibiting apoptosis and modulating the immune balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Irradiation-induced immunosuppression often occurs during radiotherapy in patients, which would increase the risk of opportunistic infections. Many Chinese herbal prescriptions or natural extracts have recently attracted increased radiation protection and therapy attention due to their low toxicity. AIM OF THE STUDY: The present study aimed to investigate the protective effects of Yiqi Jiedu (YQJD) decoction on spleen injury induced by 2 Gy 60Co γ ray in mice. MATERIALS AND METHODS: A total of 180 Balb/c mice were randomly divided into five groups: blank control (Ctrl), model (IR), positive drug (IRA), low-dose YQJD decoction (IRL), and high-dose YQJD decoction (IRH). After a ten-day intervention, mice were exposed to a single dose of total body irradiation (2 Gy) and sacrificed on the 1st, 3rd, and 7th day after irradiation. The indicators include general observations and body weight, changes in peripheral hemogram, index and histopathology examination of the spleen, distribution of lymphocyte subsets, cytokine levels, and apoptosis in the spleen. RESULTS: In comparison to the Ctrl group, the body weight, spleen index, peripheral blood cell, and splenocyte quantities decreased significantly after exposure, accompanied by a notable increase of apoptosis in spleen cells. Moreover, ionizing radiation also broke the balance of CD4+/CD8+, Th1/Th2, and Th17/Treg, triggering immune imbalance and immunosuppression. The above injuries occurred on the 1st day after exposure, worsened on the 3rd, and were relieved on the 7th day. However, the pretreatment of YQJD decoction increased the spleen index, improved the spleen structure, and inhibited radiation-induced apoptosis after exposure. Additionally, YQJD decoction has shown its ability to promote immunological balance recovery following exposure by regulating CD4+/CD8+, Th1/Th2, and Th17/Treg ratios, which may minimize the risk of infection. In addition, the high-dose of YQJD decoction showed a better protective effect than the low-dose group. CONCLUSION: The protective effects of YQJD decoction on 2 Gy 60Coγray induced spleen injury were confirmed in this study. This mechanism may be related to inhibiting apoptosis and modulating immune balance. This exploration might provide new insights into the use of Chinese herbs on radioprotection of the immune system.

A Chinese herbal prescription Yiqi Jiedu decoction attenuates irradiation induced testis injury in mice.

OBJECTIVE: Yiqi Jiedu (YQJD) decoction is a Chinese herbal prescription, based on an experienced expert of traditional Chinese medicine. It is used for the injuries caused by radiotherapy. The current study was designed to investigate the protective effects of YQJD decoction on radiation damage of testis in mice, and to explore its potential mechanisms. METHODS: Mice were randomly divided into blank control group (Ctrl), model group (IR), positive drug group (IRA), and YQJD decoction group (IRY). After 10-day period intervention, they were whole-body irradiated with 2 Gy 60Co γ-rays and sacrificed on 7th day after irradiation. The indicators including the index and histopathology examination of testis, spermatogenic cell types and apoptosis, and the expression of TLR5, MyD88, NF-κB, TNF-α, IL-6 and Bcl-2 in testis. RESULTS: The testis atrophied significantly on 7th day of exposure to radiation, while YQJD decoction promoted the recovery of testis index and structure. Moreover, spermatogenic cell types and apoptosis had significant changes after irradiation. YQJD decoction protected the testicular function of spermatogenesis, as while as reduced the apoptosis rate of spermatogenic cells. In addition, RT-PCR and immunohistochemical analysis showed that YQJD decoction up-regulated the expression of TLR5 in testis. The levels of TLR5's downstream factors were also up-regulated in YQJD decoction group, which indicated that TLR5 signaling pathway might play an important role in the protective effects of YQJD decoction. CONCLUSIONS: The results showed that YQJD decoction attenuated irradiation induced testis injury in mice. Its potential mechanism was related to TLR5 signaling pathway.

Identification of Key Pathways and Genes in L4 Dorsal Root Ganglion (DRG) After Sciatic Nerve Injury via Microarray Analysis.

Background: Peripheral nerve injury (PNI) has devastating consequences. Dorsal root ganglion as a pivotal locus participates in the process of neuropathic pain and nerve regeneration. In recent years, gene sequencing technology has seen rapid rise in the biomedicine field. So, we attempt to gain insight into in the mechanism of neuropathic pain and nerve regeneration in the transcriptional level and to explore novel genes through bioinformatics analysis. Methods: The gene expression profiles of GSE96051 were downloaded from GEO database. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. Results: Our results showed that both IL-6 and Jun genes and the signaling pathway of MAPK, apoptosis, P53 present their vital modulatory role in nerve regeneration and neuropathic pain. Noteworthy, 13 hub genes associated with neuropathic pain and nerve regeneration, including Ccl12, Ppp1r15a, Cdkn1a, Atf3, Nts, Dusp1, Ccl7, Csf, Gadd45a, Serpine1, Timp1 were rarely reported in PubMed database, these genes may provide us the new orientation in experimental research and clinical study. Conclusions: Our results may provide more deep insight into the mechanism and a promising therapeutic target. The next step is to put our emphasis on an experiment level and to verify the novel genes from 13 hub genes.

Regulatory effect of a Chinese herbal medicine formula on non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease. The Chinese herbal medicine (CHM) Dachaihu decoction (DCHD) has been proved to treat NAFLD with good efficacy in previous studies. Based on the TCM principle of formula formation, we divided DCHD into soothing liver part, invigorating spleen part, and dredging intestine part. Marshall officially proposed the concept of "intestinal-hepatic axis", which systematically explains the interactions between the intestine and liver. We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine. Thus, we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model. AIM: To investigate the effects of a CHM formula (a decoction of Chinese thorowax root, scutellaria root, and white peony root) on NAFLD and its regulatory effect on the "intestinal-liver" axis. METHODS: Sixty rats were randomly divided into control, model, pioglitazone hydrochloride (PH), and CHM (a decoction of Chinese thorowax root, scutellaria root, and white peony root) groups. An NAFLD rat model was established using a high-fat high-fructose diet for 16 wk. From the 13th week, rats were administered with PH or a decoction of Chinese thorowax, scutellaria, and white peony root (CHM group) for 4 wk. Rats in the control group and model group were administered with an equal volume of distilled water. At the end of the study, blood was collected via the abdominal aorta. Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin (HE) staining, Oil red O staining, and Masson staining. In addition, blood lipids, liver function markers, and triglyceride (TG) in liver tissues were analyzed. The levels of transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4), and nuclear factor-kappa B (NF-кB) in liver tissues and secreted immunoglobulin A (sIgA) in intestinal tissues were analyzed by ELISA, and protein and mRNA expression of occludin and zonula occludens-1 (ZO-1) in the intestine were measured using Western blot and reverse transcription-quantitative polymerase chain reaction, respectively. The endotoxin level in plasma was detected by endpoint chromogenic assay. RESULTS: Compared to the normal control group, the liver coefficient, serum TG, total cholesterol (TC), low density lipoprotein (LDL), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues increased significantly in the model group, while serum high density lipoprotein (HDL), intestinal sIgA, and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group (P < 0.01). PH and CHM attenuated the elevated liver coefficient, serum TG, TC, LDL, AST, and ALT, blood glucose, plasma endotoxin, and the levels of TG, TNF-α, TGF-ß, NF-kB, and TLR4 in liver tissues and increased serum HDL levels compared to the model group (P < 0.01). Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups (P < 0.01). CONCLUSION: The decoction of Chinese thorowax root, scutellaria root, and white peony root is beneficial in regulating lipid metabolism and liver function, which indicates that it has a good effect on the liver. To a certain extent, this CHM formula can affect both the liver and intestine, while its effect on the liver is superior to that on the intestine.

Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials.

PURPOSE: It is an open question whether cell transplantation can provide safety and effective outcome to spinal cord injury (SCI) patient which has remained controversial for almost 40 years. This study aimed to evaluate the safety and efficacy of cell transplantation in SCI patients. METHOD: Studies of the cell transplantation for SCI were retrieved from PubMed, Embase, Medline, Cochrane Library and analyzed quantitative data by Review Manager 5.3. RESULTS: Twenty-one clinical controlled studies with 973 patients were included. The pooled results suggested that cell transplantation significantly improved ASIA score, ASIA motor score, ASIA sensory score, Barthel Index score, residual urine volume, rehabilitative time of automatic micturition. Furthermore, subgroup analysis indicated that the stem cells exhibited more potent than the non-stem cells in spinal cord repair. Cell transplantation at more than 14 days after injury showed more significant improvements than that within 14 days from injury. The dosage of cell transplantation between 1-5 × 107 and 10-20 × 107 was the potent quantity for the patient with SCI. Intrathecal injection and intravenous + intrathecal injection showed more superior to the other method. The top 5 adverse events were febrile reaction (11.5%), neurologic pain (11.3%), headache (2.6%), neurologic deterioration (2.4%), and rigidity or spasticity (1.6%). CONCLUSION: Cell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1-5 × 107 and 10-20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient. These slides can be retrieved under Electronic Supplementary Material.

Retraction Note: Comparison of two FDA-approved interspinous spacers for treatment of lumbar spinal stenosis: Superion versus X-STOP-a meta-analysis from five randomized controlled trial studies.

The Editor-in-Chief has retracted this article [1] because of an error in the meta analysis. Re-examination of the data has showed that there is only one published randomized controlled trial comparing Superion with XStop. Due to a misunderstanding of the published clinical data, the conclusions drawn in the article are incorrect. Author Xing Yu approved this retraction, none of the other authors replied to correspondence from the publisher about this retraction.

Comparison of two FDA-approved interspinous spacers for treatment of lumbar spinal stenosis: Superion versus X-STOP-a meta-analysis from five randomized controlled trial studies.

BACKGROUND: Decompressive laminectomy (DI) is a standard operation for lumbar spinal stenosis (LSS) patient with severe claudication symptoms for many years. However, patients whose symptom severity does not meet undergoing invasive surgery make therapeutic options into dilemma. Interspinous spacers (ISP) bridge the gap between surgical interventions and CC in management of LSS. In our study, we aim to systematically assess the two FDA-approved interspinous spacers for treatment of lumbar spinal stenosis: Superion versus X-STOP. METHODS: Electronic databases, including PubMed, Embase, MEDLINE, Cochrane Library were searched to retrieve clinical trials concerning the comparison between Superion and X-STOP in treatment for lumbar spinal stenosis before April 2017. The following outcome measures were extracted: (1) Zurich Claudication Questionnaire (ZCQ) patient satisfaction score, (2) axial pain severity, (3) extremity pain severity, (4) back-specific functional impairment, (5) reoperation, and (6) complication. The data analysis was conducted with Review Manager 5.3. RESULTS: Five randomized controlled trials (RCTs) with 1118 patients were included in this meta-analysis. The pooled analysis indicated that the Superion group is superior to X-STOP in axial pain severity (SMD: 0.03; 95% CI 0.15, 0.45; p < 0.0001, I2 = 41%, p = 0.16), ZCQ patient satisfaction score (SMD: 0.23; 95% CI 0.08, 0.38; p = 0.002, I2 = 0%, p = 0.61). However, Superion group showed similarity outcome in extremity pain severity (SMD: 0.18; 95% CI - 0.06, 0.43; p = 0.14, I2 = 62%, p = 0.05), back-specific functional impairment (SMD: 0.04; 95% CI - 0.10, 0.19; p = 0.56, I2 = 0%, p = 0.77), reoperation rate (RR: 1.10; 95% CI 0.82, 1.48; p = 0.51, I2 = 19%, p = 0.30), and complication (RR: 0.98; 95% CI 0.63, 1.53; p = 0.92, I2 = 0%, p = 0.83). CONCLUSION: Both the Superion and X-STOP interspinous spacers can relieve symptoms of LSS. In addition, the Superion spacer may represent a promising spacer for patient with LSS. As we know, the effectiveness and safety of ISP is still considered investigational and unfavor clinical results in the medical literature may continue to limit the appeal of IPS to many surgeons in the future. However, because of the advantage of IPS technique, it will win a wide place in the future degenerative lumbar microsurgery.

Association of BAFF and IL-17A with subphenotypes of primary Sjögren's syndrome.

AIM: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting exocrine glands. Both autoreactive T cells and B cells are involved in the development of pSS, but their exact contribution to the pathogenesis is not clear. Here, we aimed to investigate the association of B-cell activating factor (BAFF) and interleukin (IL)-17A with subphenotypes of pSS. METHODS: Peripheral blood samples were collected from 31 pSS patients and 28 healthy controls. The serum levels of BAFF and IL-17A were quantified by sandwich ELISA. RESULTS: The increased circulating BAFF levels are associated with higher immunoglobulin G (IgG) levels (P = 0.0167) and anti-Ro/SS antigen A autoantibody (P = 0.032), while the elevated circulating levels of IL-17A are associated with lower C3 levels (P = 0.0213) and higher focus score of salivary gland tissue (P = 0.002). CONCLUSION: Our results show that BAFF and IL-17A are associated with different subphenotypes of pSS, suggesting both humoral and cellular immune response are involved in the pathogenesis of pSS.

Influence of Sanao Tang on urine volume and expression of aquaporin 2 in rats with respiratory function impairment induced by passive smoking and lipopolysaccharide.

OBJECTIVE: To investigate the effect of Sanao Tang (SAT) on urine volume and the expression of aquaporin- 2 (AQP2) in rats with lung dysfunction induced by passive smoking and lipopolysaccharide. METHODS: Totally 45 healthy Specific pathogen Free Wistar Rats were randomized into 3 groups: normal control group, model group and SAT group. A rat model of respiratory dysfunction induced by exposure to cigarette smoking and lipopolysaccharide (LPS). Lavage of decoction of the Chinese medicine was performed for rats in the SAT group. Anires 2005 System was used to analyze the pulmonary function. Urine of rats was collected through metabolism cage method. Enzyme-linked immunosorbent assay (ELISA) was used to determine content of antidiuretic hormone (ADH), angiotensin Ⅱ (AngⅡ), atrial natriuretic factor (ANP), endothelin 1 (ET-1), nitric oxide (NO) and prostaglandin E2 (PGE2) in serum, lung and kidney. The expression of AQP2 in rat renal tissue was determined with real-time fluorescence quantitative PCR (RT-PCR). RESULTS: (a) In comparison with the normal control, It was found that enforced vital capacity (FVC), 1-second forced expiratory volume/forced vital capacity% (FEV(1)/FVC%), 24 h urine volume content of NO and PGE2 were decreased, while AQP2mRNA level and content of ADH, Agn Ⅱ, ANP and ET-1 were increased in the model group with statistical significance (P < 0.05). (b) In comparison with the model group, It was found that FVC, FEV(1), FEV(1)/FVC%, 24 h urine volume, content of PGE2 and NO decreased, while AQP2mRNA level, content of ANP, ADH and Ang Ⅱ decreased in the SAT group with statistical significance (P < 0.05). CONCLUSION: SAT might effectively regulate the urine volume in the modeled rats; ADH, Ang Ⅱ, ANP, ET-1, NO and PGE2 might play an important role in the regulation on urine volume by lungs. This might be the mechanisms underpinning the function of lung governing water passage in terms of the theory of Traditional Chinese Medicine.

Da-bu-yin-wan and qian-zheng-san to neuroprotect the mouse model of Parkinson's disease.

Da-Bu-Yin-Wan (DBYW) and Qian-Zheng-San (QZS), two classic traditional Chinese medicinal formulas, were clinically employed to treat Parkinson's disease (PD). Our previous studies demonstrated neuroprotective effects of them on mitochondrial function in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The purpose of this research was to investigate their possible mechanisms in the light of mitochondrial ATP-sensitive potassium (mitoKATP) channels. The neuroprotective effect of DBYW and QZS on dopamine (DA) neurons in substantia nigra (SN) in the MPTP-induced PD mice was investigated by behavioral test (pole test) and immunohistochemistry. Adenosine triphosphate (ATP) level in the midbrain tissue was detected by firefly luciferase method. MitoKATP channel subunits SUR1 and Kir6.2 mRNA and protein expressions were tested by real-time PCR (RT-PCR) and Western blot. It was observed that DBYW and/or QZS served to ameliorate MPTP-induced behavioral impairment and prevent the loss of substantia nigra dopamine neurons, as well as increase ATP level in the midbrain tissue and downregulate SUR1 expression at mRNA and protein levels with no marked influence on Kir6.2. We concluded that DBYW and QZS exhibit neuroprotective effects probably through the regulation of ATP level and mitoKATP channel subunit expressions.