Background: Osteoarthritis (OA) is a common chronic age-related joint disease characterized primarily by inflammation of synovial membrane and degeneration of articular cartilage. Accumulating evidence has demonstrated that Danggui-Shaoyao-San (DSS) exerts significant anti-inflammatory effects, suggesting that it may play an important role in the treatment of knee osteoarthritis (KOA). Methods: In the present study, DSS was prepared and analyzed by high-performance liquid chromatography (HPLC). Bioinformatics analyses were carried out to uncover the functions and possible molecular mechanisms by which DSS against KOA. Furthermore, the protective effects of DSS on lipopolysaccharide (LPS)-induced rat chondrocytes and cartilage degeneration in a rat OA model were investigated in vivo and in vitro. Results: In total, 114 targets of DSS were identified, of which 60 candidate targets were related to KOA. The target enrichment analysis suggested that the NF-κB signaling pathway may be an effective mechanism of DSS. In vitro, we found that DSS significantly inhibited LPS-induced upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP3), and matrix metalloproteinase-13 (MMP13). Meanwhile, the degradation of collagen II was also reversed by DSS. Mechanistically, DSS dramatically suppressed LPS-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway. In vivo, DSS treatment prevented cartilage degeneration in a rat OA model. Conclusions: DSS could ameliorate the progression of OA through suppressing the NF-κB signaling pathway. Our findings indicate that DSS may be a promising therapeutic approach for the treatment of KOA.
Accumulating studies have demonstrated serum exosomal microRNAs (miRNAs) represent novel biomarkers for various diseases. In this study, we aimed to explore the feasibility of using serum exosomal miRNAs as novel serological biomarkers for steroid-induced osteonecrosis of femoral head (SONFH). We identified the characters of exosomes which were obtained from fresh serum of 5 systemic lupus erythematosus (SLE) patients without SONFH, 5 SLE patients with SONFH (SLE-SONFH) and 5 healthy ones. Comprehensive exosomal miRNA sequencing was performed to profile the differentially expressed miRNAs in the three groups. We then validated the expression levels of selected miRNAs by qRT-PCR. Furthermore, KEGG pathway, GO annotation, protein-protein interaction (PPI) network, module analysis and miRNAs-mRNAs interaction network were built to analyze the potential targets and mechanism. Sequencing data conveyed that hsa-miR-135b-5p, hsa-miR-150-5p, hsa-miR-509-3-5p, hsa-miR-514a-3p and hsa-miR-708-5p were significantly differentially expressed in the three groups. The results of qRT-PCR for the first time confirmed that the expression of hsa-miR-135b-5p was strikingly up-regulated in SLE-SONFH group which were consistent with miRNA sequencing results. In addition, bioinformatics analysis indicated that the enriched functions and pathways of the most differentially expressed miRNAs including Wnt, MAPK as well as Hippo signaling pathway. The top five hub genes (FGF2, PTEN, HACE1, VAMP2, and CBL) were part of module of the PPI network, which consisted of 713 nodes and 2191 edges. In conclusion, this study provides a novel and fundamental serum exosomal miRNAs profile of SONFH and hsa-miR-135b-5p may be identified as a unique diagnostic biomarker for SONFH.
At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.
2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.
To investigate the mechanism of osteonecrosis of the femoral head caused by alcohol and the therapeutic effects of the method of invigorating the kidney.The osteoblast-like cells were intervened with 0.3, 0.9, 1.5 mol/L alcohol and observed by flow cytometry and light microscopy and electro microscopy. The cells intervened by 0.15 mol/L alcohol were treated with liuweidihuang pill medicated serum and observed by flow cytometry and light microscopy and electro microscopy.Apoptosis rate and the degree of cell necrosis had positive correlation with the concentration and the acting time of alcohol. The polymorphism of cells wer turned into roundness, and the cellular ecphyma was shortened and thinning, ribosome and endocytoplasmic reticulum were diminished. Part of the ruffle in mitochondria was disappeared. After treatment, the cellular ecphyma was recovered and the endoplasmic reticulum and golgi apparatus were visible.The osteoblast-like cells could be necrosis and apoptosis by the alcohol and were positive correlation with the intervened concentration and acting time. Chinese medicine with method of invigorating the kidney has effect on rehabilitating the cellular activity.
Systemic lupus erythematosus (SLE) is a refractory immune disease, which is often complicated with osteonecrosis of the femoral head (ONFH). Curcumin, the most active ingredient of Curcuma longa with a variety of biological activities, has wide effects on the body system. The study is aimed at exploring the potential therapeutic targets underlying the effect of curcumin on SLE-ONFH by utilizing a network pharmacology approach and molecular docking strategy.Curcumin and its drug targets were identified using network analysis. First, the Swiss target prediction, GeneCards, and OMIM databases were mined for information relevant to the prediction of curcumin targets and SLE-ONFH-related targets. Second, the curcumin target gene, SLE-ONFH shared gene, and curcumin-SLE-ONFH target gene networks were created in Cytoscape software followed by collecting the candidate targets of each component by R software. Third, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Eventually, a gene-pathway network was constructed and visualized by Cytoscape software; key potential central targets were verified and checked by molecular docking and literature review.201 potential targets of curcumin and 170 related targets involved in SLE-ONFH were subjected to network analysis, and the 36 intersection targets indicated the potential targets of curcumin for the treatment of SLE-ONFH. Additionally, for getting more comprehensive and accurate candidate genes, the 36 potential targets were determined to be analyzed by network topology and 285 candidate genes were obtained finally. The top 20 biological processes, cellular components, and molecular functions were identified, when corrected by a P value ≤ 0.05. 20 related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. Molecular docking showed that the top three genes (TP53, IL6, VEGFA) have good binding force with curcumin; combined with literature review, some other genes such as TNF, CCND1, CASP3, and MMP9 were also identified.The present study explored the potential targets and signaling pathways of curcumin against SLE-ONFH, which could provide a better understanding of its effects in terms of regulating cell cycle, angiogenesis, immunosuppression, inflammation, and bone destruction.
Kaempferol is a dietary flavonoid that can function as a selective estrogen receptor modulator (SERM). Estrogen-related receptors alpha and gamma (ERRα and ERRγ) are orphan nuclear receptors that play important roles in mitochondrial biogenesis and cancer development. We have shown that kaempferol can functionally antagonize the activities of ERRs based on both response element reporter systems and target gene analysis. Kaempferol modulation of mitochondrial function and suppression cancer cell growth has been confirmed. These findings suggest that kaempferol may exert their anti-cancer activities through antagonizing ERRs activities.
Objective To study the safety and efficacy of laparoscopic partial pancreatectomy for the treatment of persistent hyperinsulinemic hypoglycemia of infancy (PHHI).Methods Between September 2008 and April 2011,the laparoscopic partial pancreatectomy was performed on 4 infants with PHHI.The levels of blood sugar and insulin were followed-up and retrospectively analyzed in this study.Results The operating time ranged from 170 to 190 min,and blood loss during surgery was minimal without necessity for blood transfusion.The length of hospital stay after operation was 12 to 24 days.The duration of postoperative abdominal drainage was 2 to 7 days.The level of fasting blood glucose after surgery was higher than that before surgery (7.5mmol/L vs.2.8mmol/L),The level of fasting insulin after surgery was lower than that before surgery (7.2 mU/L vs.77.4 mU/L),The patients were followed up for 2 to 32 months.The 3 patients underwent 90％ pancreatectomy had normal blood glucose and insulin.The patient underwent focal resection was performed secondary pancreatectomy due to recurrence of hypoglycemia,and had normal blood glucose and insulin after operation.Conclusions Laparoscopic partial pancreatectomy is safe and effective for the treatment of PHHI in children.
Key words:
Laparoscopes; Persistent hyperinsulinemic hypoglycemia of infancy; Treatment outcome
Mammalian cells including human cancer cells are usually transported in cryovials on dry ice or in a liquid nitrogen vapor shipping vessel between different places at long distance. The hazardous nature of dry ice and liquid nitrogen, and the associated high shipping cost strongly limit their routine use. In this study, we tested the viability and properties of cells after being preserved or shipped over long distance in Matrigel mixture for different days. Our results showed that cells mixed with Matrigel at suitable ratios maintained excellent viability (>90%) for one week at room temperature and preserved the properties such as morphology, drug sensitivity and metabolism well, which was comparable to cells cryopreserved in liquid nitrogen. We also sent cells in the Matrigel mixture via FedEx service to different places at ambient temperature. Upon arrival, it was found that over 90% of the cells were viable and grew well after replating. These data collectively suggested that our Matrigel-based method was highly convenient for shipping live cells for long distances in semi-solid gel condition and at ambient temperature.
Objective To investigate the single nucleotide polymorphism(SNP) in the promoter of chemokine CXCL10 G-201A,and explore the relationship between the SNP and the chronicity and severity of hepatitis B virus(HBV) infection.Methods Blood samples were collected from 792 patients with HBV infection,including 200 with acute hepatitis B(AHB),200 with mild/moderate chronic hepatitis B(CHB-M),192 with severe chronic hepatitis B(CHB-S) and 200 with acute liver failure of chronic hepatitis(ACLF),and 300 healthy people were enrolled as normal control(NC).DNA were extracted and subjected to PCR amplification of fragment containing C-1596 site that links with G-201 variation,followed by restriction fragment length polymerase(RFLP) analysis.Simultaneously,400 samples were randomly extracted from various groups for direct sequencing of G-201 variation.The consistency of SNP typing results of the two methods was analyzed.Results Variation rates of G-201A were 17.77% for AHB group,25.26% for CHB-M group,26.59% for CHB-S group,21.28% for ACLF group,and 13.82% for NC group.The overall P value obtained from the general χ2 test among the 5 groups was 0.0037.The correlation test(P=0.0015) demonstrated that the variation rate was related to different disease status,and the linear trend test(P=0.0029,Z=-2.9748) indicated an increasing trend of variation rate with the disease progression.Paired comparison showed that the differences in variation rate between CHB-M and NC(P=0.0024),CHB-S and NC(P=0.0007),ACLF and NC(P=0.0428),as well as CHB-S and CHB(P=0.0488) were statistically significant.Direct PCR sequencing showed 98.68% identity with the results from PCR-RFLP.Kappa test(U=58.425,P < 0.05) indicated that the consistency of the two assays met the statistical requirements.Conclusion The G-201A variation in CXCL10 promoter is related to chronicity of HBV infection,and the relations between the variation and the severity of HBV infection remains to be further clarified.
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