A hybrid bacterium with tumor-associated macrophage polarization for enhanced photothermal-immunotherapy

Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.

TL1A/TNFR2 Axis Enhances Immunoregulatory Effects of Bone Marrow Derived Mesenchymal Stem Cell by Indian Hedgehog Signaling Pathway

Background and Objectives@#The immunomodulatory potential of mesenchymal stem cells (MSCs) can be regulated by a variety of molecules, especially cytokines. The inflammatory cytokine, TNF-like ligand 1A (TL1A), has been reported as an inflammation stimulator in-multiple autoimmune diseases. Here, we studied the effects of TL1A/TNF-receptor 2 (TNFR2) pathway on the therapeutic potency of bone marrow-derived MSCs (BMSCs). @*Methods@#and Results: BMSCs, fibroblast-like synoviocytes (FLSs), and H9 and jurkat human T lymphocytes were used in this study. BMSCs paracrine activities, differentiation, proliferation, and migration were investigated after stimulation with TL1A, and intervened with anti-TNFR2. Additionally, the effects of TL1A on BMSCs therapeutic potency were evaluated by treating RA-FLSs, and H9 and jurkat T cells with TL1A-stimulated BMSCs conditioned medium (CM). Indian hedgehog (IHH) involvement was determined by gene silencing and treatment by recombinant IHH (rIHH). TL1A induced BMSCs stemness-related genes, COX-2, IL-6, IDO, TGF-β and HGF through TNFR2. Also, TL1A corrected biased differentiation and increased proliferation, and migration through TNFR2. Meanwhile, CM of TL1A-stimulated BMSCs decreased the inflammatory markers of RA-FLSs and T cells. Moreover, TL1A-stimulated BMSCs experienced IHH up-regulation coupled with NF-κB and STAT3 signaling up-regulation, while p53 and oxidative stress were down-regulated. Furthermore, treatment of BMSCs by rIHH increased their anti-inflammatory effects.More importantly, knockdown of IHH decreased the ability of TL1A-stimulated BMSCs to alleviating the inflammation in RA-FLSs and T cells. @*Conclusions@#This study reports the effects of TL1A/TNFR2 pathway on the biological behaviors and therapeutic potency of BMSCs through IHH. These findings could introduce novel procedures to increase the stemness of MSCs in cellular therapy.

Interleukin-17 expression induced by orthodontic force in periodontal ligament in different periodontal condition / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate interleukin (IL)-17 expression induced by orthodontic force in periodontal ligament under different periodontal conditions.</p><p><b>METHODS</b>Seventy-seven male SD rats were divided randomly into 5 groups: healthy movement group (HM), active periodontitis movement group (PM) recovery periodontitis movement group (RM), positive control group (PC) and normal control group (NC). Active periodontitis was set up by means of ligature + susceptible bacteria + suger water in PM, PC and RM groups. This stimulating factor was removed in RM group. NiTi spring was used to apply 0.49 N mesial force to move upper first molar of the rats in HM, PM and RM groups. HM, PM and RM group rats were sacrificed on day 3 (d3), day 7 (d7) and day 14 (d14). Expression changes of IL-17 in periodontal tissue in each group were measured using immunohistochemical stain and real time fluorescence quantitative PCR.</p><p><b>RESULTS</b>IL-17 expression in periodontal ligament showed more positively in PM and RM groups compared with NC, PC and HM groups. No difference was found in the expression of IL-17 mRNA in NC (1.00 ± 0.00) (P > 0.05), except in HM d14 (1.00 ± 0.07) and RM d14 (1.19 ± 0.15). Higher expression of IL-17 mRNA (P < 0.05) was found in other groups. The expression of IL-17 mRNA in RM d3 and d7 increased more than that in HM group in the same period (P < 0.05) and it decreased significantly (P < 0.05) compared with that in PM groups in the same period.</p><p><b>CONCLUSIONS</b>IL-17 was involved in the regulation of orthodontic tooth movement in different periodontal conditions. Orthodontic force caused limited increase of IL-17 mRNA expression in recovery phase of periodontitis at early stage, then back to normal. However, in active inflammatory periodontal tissue, orthodontic force kept IL-17 mRNA at high level.</p>

Assessment of short-term results of Tos modified combined approach tympanoplasty / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To observe the short-term results of Tos modified combined approach tympanoplasty (MCAT) in chronic suppurative otitis media.@*METHOD@#This study is an observational study. The data of 26 patients (28 ears) underwent MCAT were collected. The surgical techniques, complications and preoperative and postoperative air-bone gap (ABG) were analyzed.@*RESULT@#Of 28 ears, 26 ears (92.86%) get dry after surgery. 3 ears (10.71%)repaired tympanic membranes and reperforate postoperatively in which 2 minimal perforations were cured to close up patient treatment. One ear develops posterosuperior retraction pocket and one ear re-occurs cholesteatoma. One ear occurs blunting in the anterior sulcus and one ear has lateralization of the tympanic membrane. There are no hearing worsen and facial nerve palsy. For hearing, the postoperative pure tone threshold is better than preoperation (42.8 +/- 17.97 vs 47.49 +/- 18.01, P < 0.05) and postoperative ABG shrinks significantly (19.76 +/- 7. 49 vs 30.65 +/- 10.02, P < 0.01).@*CONCLUSION@#Based on the short-term results, Tos' MCAT can successfully dissect the diseases of tympanic cavity and mastoid and develop a stable aerating middle ear with a complete hearing conduction. It is safe and feasible in the treatment of chronic suppurative otitis media, as well as in the poor-pneumatic mastoid.

Expanding military medical science and technology to non-traditional security realm / 中华医学科研管理杂志

This paper discussed the great strategic significance of expanding the military medical science and technology to the non-traditional security realm, analyzed the extent and content of the expansion. evaluated the scientific and technological foundation of the military medicine in the non-traditional security realm as well as proposed some principal measures of strengthening the expansive management.