The tumor microenvironment (TME) is the internal environment of malignant tumor progression, and the host antitumor immune response and normal tissue destruction occur in the TME. Tumor-infiltrating lymphocytes (TIL) is a crucial component of the TME and reflect the host antitumor immune response. The purpose of this study was to discuss the methodology for TIL evaluation and assess the prognostic value of TIL in gastric cancer. In total, we reviewed 1,033 gastrectomy cases between 2002 and 2008 at the Third Affiliated Hospital of Soochow University. To understand the prognostic value of TIL in gastric cancer (GC), TIL were assessed by optical microscopy, and verified by immunohistochemistry. There is no current consensus on TIL scoring in GC. In this study, we discussed a TIL evaluation system that includes an analysis of the amount and percentage of TIL in a tumor. Ultimately, 439 (52.7%) cases showed high levels of TIL and 394 (47.3%) cases had low levels. There was a statistically significant relationship among TIL, tumor size, histological grade, LN metastasis, nerve invasion, tumor thrombus, pTN stage, and WHO subtypes (p < 0.001, respectively). TILhi was a positive significant predictor of overall survival (OS) in Kaplan–Meier survival analysis (P < 0.001) and multivariate Cox regression analysis (HR = 0.431, 95% CI: 0.347–0.534, P < 0.001). After surgery, patients with malignant tumors underwent chemoradiotherapy according to standard therapeutic guidelines based on TNM stage. The TNM scoring system cannot reflect the full information of TME; therefore, TIL can be used as a diagnostic supplement. We constructed a nomogram model that showed more predictive accuracy for OS than pTN stage. In summary, this study proves that high levels of TIL are associated with a positive prognosis and that TIL reflect the protective host antitumor immune response.

Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis.

This review aimed to evaluate the efficacy of low-level laser therapy (LLLT) for accelerating tooth movement during orthodontic treatment. An extensive electronic search was conducted by two reviewers. Randomized controlled trials (RCTs) and quasi-RCTs concerning the efficacy of LLLT for accelerating tooth movement during orthodontic treatment were searched in CENTRAL, Medline, PubMed, Embase, China Biology Medicine Disc (CBM), China National Knowledge Infrastructure (CNKI), and Google Scholar. Six RCTs and three quasi-RCTs, involving 211 patients from six countries, were selected from 173 relevant studies. All nine articles were feasible for the systematic review and meta-analysis, five of which were assessed as moderate risk of bias, while the rest were assessed as high risk of bias. The mean difference and the 95 % confidence interval (95 % CI) of accumulative moved distance of teeth were observed among all the researches. The results showed that the LLLT could accelerate orthodontic tooth movement (OTM) in 7 days (mean difference 0.19, 95 % CI [0.02, 0.37], p = 0.03) and 2 months (mean difference 1.08, 95 % CI [0.16, 2.01], p = 0.02). Moreover, a relatively lower energy density (5 and 8 J/cm(2)) was seemingly more effective than 20 and 25 J/cm(2) and even higher ones.

The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva-derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy.

To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils. Furthermore, we found that Toll-like receptor 2 (TLR2) and TLR4 mediated the activation of the kinases NF-κB, p38, ERK, and JNK and the production of IL-6, IL-23, and IL-17 in neutrophils infected with MTB H37Rv. Autocrine IL-17 produced by neutrophils played a vital role in inhibiting MTB H37Rv growth by mediating reactive oxygen species production and the migration of neutrophils in the early stages of infection. However, IL-17 production by neutrophils contributed to collagen-induced arthritis development during MTB infection. Our findings identify a protective mechanism against mycobacteria and the pathogenic role of MTB in arthritis development.