Single-cell communication patterns and their intracellular information flow in synovial fibroblastic osteoarthritis and rheumatoid arthritis.

BACKGROUND: Synovial fibroblasts are critical for maintaining homeostasis in major autoimmune diseases involving joint inflammation, including osteoarthritis and rheumatoid arthritis. However, little is known about the interactions among different cell subtypes and the specific sets of signaling pathways and activities that they trigger. METHODS: Using social network analysis, pattern recognition, and manifold learning approaches, we identified patterns of single-cell communication in OA (osteoarthritis) and RA (rheumatoid arthritis). RESULTS: Our results suggest that OA and RA have distinct cellular communication patterns and signaling pathways. The LAMININ (Laminin) and COLLAGEN (Collagen) pathways predominate in osteoarthritis, while the EGF (Epidermal growth factor), NT (Neurotrophin) and CDH5 (Cadherin 5) pathways predominate in rheumatoid arthritis, with a central role for THY1 (Thy-1 cell surface antigen) +CDH11 (Cadherin 11) + cells. The OA opens the PDGF (Platelet-derived growth factors) pathway (driver of bone angiogenesis), the RA opens the EGF pathway (bone formation) and the SEMA3 (Semaphorin 3A) pathway (involved in immune regulation). Interestingly, we found that OA no longer has cell types involved in the MHC complex (Major histocompatibility complex) and their activity, whereas the MHC complex functions primarily in RA in the presentation of inflammatory antigens, and that the complement system in OA has the potential to displace the function of the MHC complex. The specific signaling patterns of THY1+CDH11+ cells and their secreted ligand receptors are more conducive to cell migration and lay the foundation for promoting osteoclastogenesis. This subpopulation may also be involved in the accumulation of lymphocytes, affecting the recruitment of immune cells. Members of the collagen family (COL1A1 (Collagen Type I Alpha 1 Chain), COL6A2 (Collagen Type VI Alpha 2 Chain) and COL6A1 (Collagen Type VI Alpha 1 Chain)) and transforming growth factor (TGFB3) maintain the extracellular matrix in osteoarthritis and mediate cell migration and adhesion in rheumatoid arthritis, including the PTN (Pleiotrophin) / THBS1 (Thrombospondin 1) interaction. CONCLUSION: Increased understanding of the interaction networks between synovial fibroblast subtypes, particularly the shared and unique cellular communication features between osteoarthritis and rheumatoid arthritis and their hub cells, should help inform the design of therapeutic agents for inflammatory joint disease.

[Dendritic Cells Promote the Proliferation of Peripheral Blood CRTH2 Cells (CD4(+)CD294(+)Th2) and Help B Cells to Secrete Immunoglobulin].

Objective：To investigate the promotive effect of dendritic cells(DCs) on proliferation of CRTH2 (CD4(+)CD294(+)Th2) cells and the influence of CRTH2 cells on secretion of immunoglobulin from B cells so as to provide a new approach for amplification and sorting of Th2 cells. Methods：DCs were induced from peripheral blood mononuclear cells, then the loaded-BCGV-Ag-DCs were cocultured with T cells, and the mixed lymphocyte reaction(MLR) was performed by CCK8 method. The phenotypes of DCs and CRTH2 cells were detected by flow cytometry. CRTH2 cells sorted by MACS were co-cultured with B cells for 5 days to detect the secretion of immunoglobulin. Results：The subsets and absolute number CRTH2 cells were significantly increased by loaded-BCGV-Ag-DCs. The levels of IgG, IgA and IgE were higher increased in supernatant of CRTH2 and B cell co-culture system than that in control group or that in transwell group(P<0.05). Conclusion：The proliferation of CRTH2 cells can be greatly promoted by loaded-BCGV-Ag-DCs, and the CRTH2 cells can help B cells to secrete IgG, IgA and IgE.

The antibiotic chloramphenicol may be an effective new agent for inhibiting the growth of multiple myeloma.

Chloramphenicol is an old antibiotic that also inhibits mammalian mitochondrial protein synthesis. Our studies demonstrated that chloramphenicol is highly cytotoxic to myeloma cells, acting in a dose- and time-dependent manner. Chloramphenicol sharply suppressed ATP levels in myeloma cells at concentrations ≥ 25 µg/mL. Colorimetric and clonogenic assays indicate that chloramphenicol inhibits growth of myeloma cell lines at concentrations ≥ 50 µg/mL, and inhibits primary myeloma cell growth at concentrations ≥ 25 µg/mL. Flow cytometry and Western blotting showed that chloramphenicol induces myeloma cell apoptosis at concentrations ≥ 50 µg/mL. Chloramphenicol increased levels of cytochrome c, cleaved caspase-9 and cleaved caspase-3, suggesting that myeloma cell apoptosis occurs through the mitochondria-mediated apoptosis pathway. It thus appears chloramphenicol is not only an old antibiotic, it is also a potential cytotoxic agent effective against myeloma cells. This suggests chloramphenicol may be an effective "new" drug for the treatment of myeloma.

Endoscopic lithotripsy for gastric bezoars by Nd:YAG laser-ignited mini-explosive technique.

Until now, there still has no standard treatment option to deal with gastric bezoars. This respective study was conducted to evaluate the safety and efficiency of Nd:YAG laser-ignited mini-explosive technique for the treatment of gastric bezoars. Two hundred sixty patients with 285 gastric bezoars were treated by endoscopic lithotripsy with Nd:YAG laser-ignited mini-explosive technique. Among the 260 patients, the 284 gastric bezoars of the 259 patients completely disappeared, with the cure rate of 99.6% after 1-2 treatments at 2-4 weeks follow-up. Only one patient, who was cured by surgery, had gastric perforation during the explosion. No intraoperative or delayed complications was found in the other 259 patients. The endoscopic lithotripsy with Nd:YAG laser-ignited mini-explosive technique is an effective, safe, and promising alternative for gastric bezoars.

Endoscopic holmium:YAG laser ablation of early gastrointestinal intramucosal cancer.

Various endoscopic techniques are being increasingly used in early gastrointestinal (GI) cancer. The holmium: yttrium-aluminum-garnet (Ho:YAG) laser has precise tissue cutting ability and good hemostatic properties and has been widely applicated to soft tissue, but the use of endoscopic Ho:YAG laser ablation for early gastrointestinal cancer has not been reported. Twenty patients with biopsy-proven early GI cancer who had a high surgical risk or refused surgery were treated by endoscopic Ho:YAG laser ablation. The tumors of all patients were confined to the mucosal layer without ulceration and without lymph node metastasis. The tumor diameter was not more than 2.5 cm. Endoscopy, endoscopic ultrasound, and computed tomography scan were performed 1-3 months after the treatment, and a biopsy was performed to evaluate the effects of the therapy. Long-term endoscopic follow-up was maintained. Complete eradication was achieved in all the 20 patients, including four patients with high-grade dysplasia associated with focal canceration, seven patients with well-differentiated squamous cell cancer, and nine patients with well-differentiated adenocarcinoma, resulting in a complete response rate of 100% at 1-3 months after treatment. No recurrence was found during 36-73 months of follow-up in all 20 patients. No operative or delayed complications were observed in any of the 20 patients. Preliminary study shows that endoscopic Ho:YAG laser ablation may be an effective, safe, and minimally invasive method for selected patients with early GI intramucosal cancer. Further research is required to confirm the safety and efficacy of this technique compared to its alternative techniques in a multicenter randomized controlled trial.

Effects of a bioartificial liver support system on acetaminophen induced acute liver failure canines.

AIM:To evaluate the safety and efficacy of the bioartificial liver support system in canines with acute liver failure (ALF).METHODS:Nine canines with acute liver failure by acetaminophen-induced received TECA-I bioartificial liver support system (BALSS) from Hong Kong TECA LTD Co. Blood was perfused through a hollow fiber tube containing (1-2)X10(10) the porcine hepatocytes.In contrast, another 10 canines with acute liver failure by Acetaminophen received drugs. Each treatment lasted 6 hours.RESULTS:BALSS treatment resulted in beneficial effects for acetaminophen-induced ALF canines with survival and with the recovery of the liver functions and tissues, and plasma ammonia decreased from 135.9&mgr;mol/L plus minus 17.5&mgr;mol/L to 65.7&mgr;mol/L plus minus 22.0&mgr;mol/L, 32.5&mgr;mol/L plus minus 8.8&mgr;mol/L, GPT from 97.8U/L plus minus 8.7U/L to 64.8U/L plus minus 11.9U/L, 19.0U/L plus minus 6.3U/L, GOT from 103.0U/L plus minus 16.7U/L to 75.7U/L plus minus 19.6U/L, 26.5U/L plus minus 5.0U/L, and AKP from 158.3U/L plus minus 12.1U/L to 114.5U/L plus minus 19.8U/L, 43.8U/L plus minus 5.6U/L during and after the treatment. In contrast, 10 ALF canines in both the drug and control groups died 1 or 2 days after treatment.CONCLUSION: TECA-1 artificial liver support system is safe and efficacious for canines with acute liver failure.