The barrier surfaces of the gastrointestinal tract are in constant contact with various microorganisms. Cytokines orchestrate the mucosal adaptive and innate immune cells in the defense against pathogens. IL-10 and IL-22 are the best studied members of the IL-10 family and play essential roles in maintaining mucosal homeostasis. IL-10 serves as an important regulator in preventing pro-inflammatory responses while IL-22 plays a protective role in tissue damage and contributes to pathology in certain settings. In this review, we focus on these two cytokines in the development of gastrointestinal diseases, including inflammatory bowel diseases (IBD) and colitis-associated cancer (CAC). We summarize the recent studies and try to gain a better understanding on how they regulate immune responses to maintain equilibrium under inflammatory conditions.

MicroRNAs have an important role in diverse biological processes including tumorigenesis. MiR-223 has been reported to be deregulated in several human cancer types. However, its biological role has not been functionally characterized in lung squamous cell carcinoma (LSCC). The following study investigates the role of miR-223-3p in LSCC growth and metastasis and its underlying mechanism. MicroRNA profiling analyses were conducted to determine differential miRNAs expression levels in LSCC tumor tissues that successfully formed xenografts in immunocompromised mice (XG) and failed tumor tissues (no-XG). RT-PCR and in situ hybridization (ISH) was performed to evaluate the expression of miR-223-3p in 12 paired adjacent normal tissues and LSCC specimens. Cell proliferation and migration were assessed by CCK-8, colony formation and Transwell assay, respectively. The role of miR-223-3p in LSCC tumorigenesis was examined using xenograft nude models. Bioinformatics analysis, Dual-luciferase reporter assays, Chromatin immunoprecipitation (ChIP) assay and Western blot analysis were used to identify the direct target of miR-223-3p and its interactions. MiR-223-3p was downregulated in LSCC tissues that successfully formed xenografts (XG) compared with tumor tissues that failed (no-XG), which was also significantly reduced in LSCC tissues compared with the adjacent normal tissues. Gain- and loss-of function experiments showed that miR-223-3p inhibited proliferation and migration in vitro. More importantly, miR-223-3p overexpression greatly suppressed tumor growth in vivo. Mechanistically, we found that mutant p53 bound to the promoter region of miR-223 and reduced its transcription. Meanwhile, p53 is a direct target of miR-223-3p. Thus, miR-223-3p regulated mutant p53 expression in a feedback loop that inhibited cell proliferation and migration. Our study identified miR-223-3p, as a tumor suppressor gene, markedly inhibited cell proliferation and migration via miR-223-3p-mutant p53 feedback loop, which suggested miR-223-3p might be a new therapeutic target in LSCC bearing p53 mutations.

Non-small cell lung cancer (NSCLC) carries a high mortality, and efficacious therapy is lacking. Therapy using chimeric antigen receptor (CAR) T cells has been used efficaciously against hematologic malignancies, but the curative effect against solid tumors is not satisfactory. A lack of antigen targets is one of the main reasons for this limited efficacy. Previously, we showed that lung-specific X (LUNX; also known as BPIFA1, PLUNC, and SPLUNC1) is overexpressed in lung cancer cells. Here, we constructed a CAR-T-cell-based strategy to target LunX (CAR^LunX T cells). CAR T cells were developed so that, upon specific recognition of LunX, they secreted cytokines and killed LunX-positive NSCLC cells. In vitro, CAR^LunX T cells displayed enhanced toxicity toward NSCLC lines and production of cytokines and showed specific LunX-dependent recognition of NSCLC cells. Adoptive transfer of CAR^LunX T cells induced regression of established metastatic lung cancer xenografts and prolonged survival. CAR^LunX T cells could infiltrate into the tumor. Also, we constructed a patient-derived xenograft model of lung cancer. After therapy with CAR^LunX T cells, tumor growth was suppressed, and survival was prolonged significantly. Together, our findings offer preclinical evidence of the immunotherapeutic targeting of LunX as a strategy to treat NSCLC.

Although accumulating evidence has indicated the intimate association between epithelial‐mesenchymal transition (EMT) and acquired resistance to chemotherapy for colorectal cancer (CRC), the underlying mechanisms remain elusive. Herein, we reported that Snail, a crucial EMT controller, was upregulated in CRC tissues. Colorectal cancer cells overexpressing Snail were found to be more resistant to 5‐fluorouracil (5‐Fu). Mechanistic studies reveal that Snail could increase the expression of ATP‐binding cassette subfamily B member 1 (ABCB1) rather than the other 23 chemoresistance‐related genes. Additionally, knockdown of ABCB1 significantly attenuated Snail‐induced 5‐Fu resistance in CRC cells. Oxaliplatin increased Snail and ABCB1 expression in CRC cells. Snail and ABCB1 were upregulated in 5‐Fu‐resistant HCT‐8 (HCT‐8/5‐Fu) cells and inhibition of Snail decreased ABCB1 in HCT‐8/5‐Fu cells. These results confirm the vital role played by ABCB1 in Snail‐induced chemoresistance. Further investigation into the relevant molecular mechanism revealed Snail‐mediated ABCB1 upregulation was independent of β‐catenin, STAT3, PXR, CAR and Foxo3a, which are commonly involved in modulating ABCB1 transcription. Instead, Snail upregulated ABCB1 transcription by directly binding to its promoter. Clinical analysis confirms that increased Snail expression correlated significantly with tumor size (P = .018), lymph node metastasis (P = .033), distant metastasis (P = .025), clinical stage grade (P = .024), and poor prognosis (P = .045) of CRC patients. Moreover, coexpression of Snail and ABCB1 was observed in CRC patients. Our study revealed that direct regulation of ABCB1 by Snail was critical for conferring chemoresistance in CRC cells. These findings unraveled the mechanisms underlying the association between EMT and chemoresistance, and provided potential targets for CRC clinical treatment.

Nesfatin-1 plays a role in the regulation of emotional states like depression. The aim of this study was to investigate the plasma nesfatin-1levels in Chinese patients with depression and healthy subjects, and to determine the possible association between the plasma nesfatin-1 level and the severity of depression. A total of 103 depressive patients and 32 healthy subjects were assessed. According to HAMD-17scores, 51, 18, and 34 patients were enrolled in the mild depression, moderate depression, and severe depression groups, respectively. Plasma nesfatin-1 levels were determined by the ELISA method. Differences between groups were compared and associations between plasma nesfatin-1 and other variables were analyzed. The plasma nesfatin-1 was significantly positively correlated with HAMD-17 score (r = 0.651). Compared with healthy controls (8.11 ± 3.31 ng/mL), the plasma nesfatin-1 level significantly increased in patients with mild depression (11.17 ± 3.58 ng/mL), with moderate depression (16.33 ± 8.78 ng/mL), and with severe depression (27.65 ± 8.26 ng/mL) respectively. Plasma nesfatin-1 level (Odds ratio [OR] = 1.269) was an independent indicator for severe depression by multivariate logistic regression analysis. The plasma nesfatin-1 level is positively correlated with the severity of depression. Plasma nesfatin-1 level may be a potential indicator for depression severity.