Estradiol is a key candidate for treating Ankylosing Spondylolisthesis with Traditional Chinese Medicine.

Some Traditional Chinese Medicine (TCM) has shown anti-inflammatory and immunosuppressive effects on Ankylosing Spondylitis (AS) treatment. Wan Bikang (WBK) and Wan Biqing (WBQ) are two traditional empirical formulas for AS. However, the mechanism of their effects on AS is largely unknown. This study deciphered the underlying common molecular mechanisms of these TCM treatments for AS. The ultra-high-performance liquid chromatography-triple/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) assays were employed to detect herbal ingredients. Target proteins of herbal ingredients were identified by ChEMBL Database. To infer the relationships between ingredients and AS-related proteins, network pharmacology was employed. Protein-protein interaction (PPI) network and core target analyses were carried out with tools Cytoscape and STRING. To find out the molecular basis and target of AS, molecular docking and an in vitro experiment were also conducted. It is found that estradiol may participate in the treatment of AS via the inhibition of inflammatory factors, and Estrogen Receptor 1 (ESR1) appears to be a key target. This research offers insight into the therapeutic mechanism of TCM formulas for AS and furthers our understanding of TCM pharmacology.

Identification of JUN as determinant of osteoarthritis and its inhibition by the Chinese herbal formulae Zhuanggu Huoxue Tang.

Synovitis is an essential feature of Osteoarthritis (OA). Increasing evidence demonstrates that synovitis plays a critical role in OA's symptoms and structural progression. However, there is no effective drug for preventing and treating synovitis. Some Chinese herbal formulae have been found to treat clinical OA effectively, however, their mode of action is still unclear. This study investigated the Chinese herbal formulae Zhuanggu Huoxue Tang (ZHT) underlying mechanisms for treating osteoarthritis. Transcriptome data and a network pharmacology analysis were used to investigate the biochemical pathways affected by ZHT during OA treatment with in vitro verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were undertaken. The interaction network of the ZHT active constituent targets was determined using Cytoscape 3.7.1 software. Molecular docking of key pathogenic proteins and components of ZHT was performed in silico to confirm the compounds' pharmaceutical activities. The results establish that JUN is a target pathway in the pathogenesis of osteoarthritis. Miltirone, one of the active ingredients of ZHT, demonstrated a suitable binding activity with JUN. Miltirone alleviates the catabolic gene expression induced by IL-1ß and IL-6 in synovial fibroblasts (FLS), validating the use of Miltirone as a therapeutic drug for osteoarthritis.

[A mouse model of spondyloarthritis induced by human cartilage proteglycan].

Objective To develop a model of spondyloarthritis (SpA) in mice, and analyze their clinical manifestations, radiological and histological features, and inflammatory cytokines expression levels. Methods Fourteen-week-old female BALB/c mice were immunized by intraperitoneal injection of human cartilage proteoglycan (PG), with their peripheral joints observed and scored 3 times a week. 45 weeks after immunization, micro-computed tomography (micro-CT) was used to scan the axial and peripheral joints, and bone mineral density (BMD) and bone volume/total volume (BV/TV) of the vertebral body were analyzed. The pathological changes of the axial and peripheral joints were evaluated by HE and Safranin-Fast Green staining. The levels of tumor necrosis factor alpha (TNF-α) and interleukin 17A (IL-17A) in serum were tested by ELISA. Results 30% (6/20) of PG-induced SpA (PGISpA) mice exhibited peripheral joint swelling and joint stiffness. Micro-CT showed reduced BMD and BV/TV of the vertebral body and new bone formation in sacroiliac and spinal joints in PGISpA compared with the control. Histological staining showed inflammatory cell infiltration and abnormal proliferation of synovial cells and chondrocytes in the peripheral joints. It also observed chondrocytes proliferation in the sacroiliac joints, and increased chondrocytes and osteoblasts in the spinal joints in PGISpA mice. TNF-α and IL-17A increased at week 20 after induction and TNF-α decreased at week 45 in the serum of induced mice, while IL-17A continued to increase. Conclusion The established model of PGISpA showed similar imaging and pathological features to those of human SpA, suggesting a role of IL-17A in the pathogenesis. This model, together with its research platform, can serve as the cornerstone for SpA and model animal studies.

Testing if Micro-CT Is Capable of Quantitating the Extent of Proteoglycan-Aggrecan Induced Axial Spondyloarthritis in Mice.

Objective: Injections of proteoglycan aggrecan (PGA) have been reported to induce axial spondyloarthritis (ax-SpA) in BALB/c mice. It is considered to be a model for radiographic ax-SpA. However, evaluation of the extent of axial disease by histopathological assessment of every intervertebral space is labor-intensive. The objective of our paper is to test the feasibility of Micro Computed Tomography (Micro-CT) in rapidly enumerating the number of intervertebral spaces affected in each mouse. Methods: Arthritis was induced in BALB/c mice by intraperitoneal injections of PGA. Involvement of several spinal segments, and selected sacroiliac and hip joints were evaluated by histopathology. The involvement of all intervertebral spaces, sacroiliac and hip joints was evaluated by Micro-CT. Results: BALB/c mice injected with PGA developed histopathology of SpA-like axial lesions, including spondylitis, sacroiliac joint arthritis and hip joint arthritis. Micro-CT allowed us to clearly enumerate the number of lesions in each mouse. Conclusion: Micro-CT allows quantitative assessment of the extent of axial involvement in PGA-induced mouse spondylitis. This can be a useful tool in assessing therapeutic interventions.

Analysis of the curative effect of percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fracture with intravertebral clefts.

ABSTRACT: Kummell's disease is a delayed vertebral collapse fracture caused by posttraumatic osteonecrosis. It is a special type of osteoporotic vertebral fracture in the elderly. This study compares and analyzes the difference in the curative effect of 2 kinds of osteoporotic vertebral compression fracture (OVCF) in the presence of fracture or not in the vertebral body, and provides a clinical reference for the application of percutaneous kyphoplasty (PKP).This research is a kind of retrospective analysis from January 2012 to January 2015, PKP was used to treat 165 patients with osteoporotic vertebral compression fracture. The patients were divided into 2 groups: Intravertebral clefts group (group A) and none-intravertebral clefts group in vertebral body (group B). Bone mineral density (BMD), bone cement injection (BCI), Visual analogue scale (VAS) score before and after surgery, anterior, central and posterior height of vertebral body (before and after surgery) and Cobb angle of injured vertebra (before and after surgery) were compared between the 2 groups.Surgeries for 165 patients in the 2 groups were successfully completed, and 226 fractured vertebrae were performed through bilateral puncture approach to strengthen the vertebral body. Intraoperative injection of bone cement (ml) was 4.25 + 1.29 (range: 2.6-7.8). There were statistically significant differences in bone cement injection quantity between the 2 groups (P < .05), and in bone cement leakage (P > .05) as well as the Postoperative VAS score (P < .05). However, There was no statistical difference in VAS score before surgery between the 2 groups (P > .05). The results indicated that the pain relief degree of OVCF patients without intravertebral clefts is better than that in the vertebral body. No statistical difference was found in Cobb Angle before and after surgery (P > .05), as well as the correction rate of the injured vertebrae before and after surgery (P > .05). There was no statistical difference in the degree of recovery of the anterior, middle and posterior margins of the injured vertebrae after surgery (P > .05).PKP treatment led to better degree of pain relief in OVCF patients without intravertebral clefts, and less bone cement was injected into the surgery.

Dysregulation of Innate Lymphoid Cells in Patients with Active Rheumatoid Arthritis and Mice with Collagen-Induced Arthritis.

Innate lymphoid cells (ILCs) have roles in many diseases and immune pathways. To determine the roles of these cells in patients with rheumatoid arthritis (RA) and mice with collagen-induced arthritis (CIA), we measured ILC subsets using flow cytometry and multiplex immunofluorescence staining. Patients with stable RA had greater proportions of ILC2s and decreased proportions of ILC1s and ILC3s (all p < 0.05). The 28-joint disease activity (DAS28) score had positive correlations with the proportion of ILC1s and negative correlations with ILC2s (both p < 0.05). ILC2s of patients with RA expressed more IL-4 than healthy controls (p < 0.05). The proportions of ILC1s and ILC2s were greater in mice with CIA (both p < 0.05), especially the ILC2s in mice without arthritis after immunization and had correlations with multiple inflammatory and anti-inflammatory cytokines. Multiplex immunofluorescence staining described the distribution of ILCs in spleen tissues. Our results indicate that dysregulation of ILCs occurs during the pathogenesis of RA and CIA.

Pickering emulsion-templated polymers: insights into the relationship between surfactant and interconnecting pores.

Pickering high internal phase emulsions (HIPEs) using micron-size polymeric particles as stabilizer were developed. By adding a small amount of surfactant to the Pickering HIPEs, macroporous polymers with a well-define open-cell structure were synthesized with these HIPEs as templates. Owing to the micron-size of the particles, the particle locations could be observed directly by laser scanning confocal microscopy. It was found that the excess and attached particles aggregated and formed thick particle layers around the droplets when the HIPE was stabilized solely by particles. These thick particle layers were extremely stable, and did not easily rupture during or after polymerization, which caused the resulting polymers to have a closed-cell structure. When a small amount of surfactant was added, it was found that the surfactant disaggregated the particles, leaving them well-dispersed in the continuous phase. Moreover, the surfactant tended to occupy the oil-water interface at the contact point of adjacent droplets, where the interconnecting pores were hence likely to be formed after consolidation of the continuous phase. This observation confirmed experimentally the mechanism of interconnecting pore formation in Pickering-HIPE-templated porous polymers proposed theoretically in previous works.

Development on PEG-modified Poly (Amino Acid) Copolymeric Micelles for Delivery of Anticancer Drug.

BACKGROUND: Polymeric micelles can provide a valid way for cancer treatment with several benefits including high water-solubility of lipophilic drugs, low unwanted effects of cytotoxic drugs by way of reduced systemic exposure and prolonged retention time in the circulatory system. OBJECTIVE: Recently, there is an increasing interest in preparing poly (ethylene glycol)-poly (amino acid) copolymeric micelles as drug delivery carriers due to their multifunctional property, easy decoration and biosafety. The copolymer contains several functional groups, which show stronger interactions with drugs or can be transferred to develop different types of the copolymers showing pH-, reduction-, thermo-sensitive, targeted or double-function properties. In addition, conjugation of drugs with these copolymers also becomes a novel modification method with the aim of higher drug loading capacity and stability. Copolymeric micelles show exciting advantages on improving a drug's water-solubility, release behavior, in vitro activity, targeted delivery pharmacokinetic property and biodistribution. In this review, we will introduce the recent development of poly(ethylene glycol)-modified poly (amino acid) copolymeric micelles as anticancer drug delivery systems containing different stimuli (such as thermo-, pH-, reduction- or special enzyme- condition) functional groups and targeting ligands to improve cellular uptake or biostablility of drug-loaded micelles. CONCLUSION: Poly (ethylene glycol)-poly (amino acid) copolymeric micelles provide an opportunity to realize anticancer drug delivery with environment-responsive and/or targeting property.

Long-term outcome of olfactory ensheathing cell transplantation in six patients with chronic complete spinal cord injury.

The aim of the study was to analyze the clinical efficacy and safety of olfactory ensheathing cell (OEC) transplantation for treating patients with chronic, complete spinal cord injury (SCI). Six patients with six chronic complete spinal cord injuries were recruited and treated with autologous OEC transplantation and followed for 24 months. The scores from before and after transplantation were analyzed. This was a self-control experiment. There was significant amelioration in the scores of the standard neurological classification of spinal cord injury made by the America Spinal Cord Injury Association (ASIA) and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) following OEC transplantation with 24 months of follow-up. No clinical complications were observed. OEC transplantation would appear to be clinically safe and may promote the neurofunctional recovery of SCI based on data from six patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Clinical application of olfactory ensheathing cells in the treatment of spinal cord injury.

OBJECTIVES: To investigate the safety and therapeutic efficacy of autologous olfactory ensheathing cell (OEC) transplantation in cervical spinal cord injury (SCI). METHODS: Patients with cervical SCI of >6 months' duration were treated with autologous OECs, injected into the area surrounding the SCI under magnetic resonance imaging guidance, twice a week for 4 weeks. Patients were evaluated before treatment and at 3, 6, 12 and 24 months post-treatment, using the American Spinal Injury Association (ASIA) Impairment Scale, the ASIA sensory and motor score and the Functional Independence Measure (FIM) score. RESULTS: Eight patients were recruited to the study. Three months after treatment, ASIA and FIM scores had improved significantly compared with pretreatment, though by 1 year no further significant improvements in the ASIA score were seen. The return of substantial sensation and motor activity in various muscles below the injury level was observed in three patients during follow-up. In addition, bladder function was restored in two patients. There were no serious complications postoperatively or during the follow-up period. CONCLUSIONS: This study provides preliminary evidence of the safety and possible efficacy of autologous OEC transplantation.

Abnormal expression of fibrinogen gamma (FGG) and plasma level of fibrinogen in patients with hepatocellular carcinoma.

UNLABELLED: Abnormal expression of genes has been related to progression of hepatocellular carcinoma (HCC). The present study investigated the mRNA expression of fibrinogen gamma (FGG) in HCC and levels of plasma fibrinogen of patients with HCC. MATERIALS AND METHODS: Northern blot and semiquantitative RT-PCR were performed to determine the mRNA transcription of FGG. The plasma fibrinogen was measured quantitatively by the von Clauss method. RESULTS: FGG was significantly up-regulated at the mRNA level in the SMMC-7721 and HepG2 HCC cell lines. FGG mRNA transcript was also up-regulated in HCC tissues when compared to non-cancerous adjacent tissues as control. The laboratory investigation of blood samples from 114 HCC patients showed significantly higher levels of plasma fibrinogen compared to healthy persons as control (3.75+/-1.41 vs. 2.90+/-0.46 g l(-1)) (p<0.01). Moreover, plasma fibrinogen increased progressively with the tumor clinical stage of HCC patients. By multivariate logistic regression analysis, a positive level of plasma fibrinogen was found to have a significant correlation with the presence of tumor thrombosis. CONCLUSION: FGG mRNA was expressed abnormally in HCC and elevated plasma fibrinogen may serve as a useful predictor of clinical progression of HCC patients.

Messenger RNA expression of translationally controlled tumor protein (TCTP) in liver regeneration and cancer.

OBJECTIVE: Translationally controlled tumor protein (TCTP) was recently reported to be involved in tumor reversion. In order to understand TCTP mRNA transcript in proliferative tissue and malignant lesions, the mRNA expression of TCTP was determined in a rat model of liver regeneration and human liver cancer tissues. In addition, the potential role of TCTP on suppression of liver cancer was investigated. MATERIALS AND METHODS: Liver regeneration model was established by a two-thirds partial hepatectomy (PH) in adult, male Sprague-Dawley rat. TCTP mRNA expression was determined by semiquantitative RT-PCR analysis. Antisense mRNA of TCTP was transfected into the SMMC-7721 liver cancer cell line. Biological assay of proliferation and cell cycle were analysed by MTT and flow cytometry, respectively. RESULTS: After PH of rats, the level of TCTP mRNA transcript was upregulated slightly in liver tissue at 1 hour followed by a high expression from 3 to 12 hours, which then decreased dramatically at 24 hours before returning to original level during liver tissue proliferation. TCTP mRNA transcript increased significantly in liver cancer tissues when compared to non-cancerous adjacent tissues as control. The transfection with antisense oligodeoxynucleotides of TCTP led to decreased proliferation of SMMC-7721 cells resulting in cell cycle arrest and pro-apoptosis. CONCLUSION: The results suggested that TCTP mRNA expression might be stage-specific in the proliferation of liver tissue but alter abnormally in cancer lesions. TCTP could be used as a potential target for suppression of liver tumorigenicity.

[On the phenomenon of lexical gap in English translation of TCM terms].

Through multi-angular analysis on the phenomena of lexical gap in English translation of TCM terms and combining with the practice in translating work, the basic principles and strategies that ought to be adopted in English translating TCM vacant terms (TCM terms lacking for counterparts) were summarized on the basis of displaying fully the intention of the terms, and their significance in researches for normalization of TCM terms translation was discussed.