The regeneration of intestinal epithelial are maintained by continuous differentiation and proliferation of intestinal stem cells (ISCs) under physiological and pathological conditions. However, little is known about the regulatory effect of intestinal microbiota on its recovery ability to repair damaged mucosal barrier. In this study, we established intestinal organoids and lamina propria lymphocytes (LPLs) co-cultured system, plus mice experiments, to explore the protective effect of Lactobacillus reuteri D8 on integrity of intestinal mucosa. We found that only live L. reuteri D8 was effective in protecting the morphology of intestinal organoids and normal proliferation of epithelial stained with EdU under TNF-α treatment, which was also further verified in mice experiments. L. reuteri D8 colonized in the intestinal mucosa and ameliorated intestinal mucosa damage caused by DSS treatment, including improvement of body weight, colon length, pathological change, and proliferation level. The repair process stimulated by L. reuteri D8 was also accompanied with increased numbers of Lgr5 and lysozyme cells both in intestinal organoids and mice intestine. Furthermore, we demonstrated that D8 metabolite indole-3-aldehyde stimulated LPLs to secret IL-22 through aryl hydrocarbon receptor (AhR) and then induced phosphorylation of STAT3 to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa. Our findings indicate L. reuteri protects intestinal barrier and activates intestinal epithelial proliferation, which sheds light on treatment approaches for intestinal inflammation based on ISCs with probiotics Lactobacillus and daily probiotic consumption in heath foods.

Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN.

The intestine is home to trillions of microorganisms, and the vast diversity within this gut microbiota exists in a balanced state to protect the intestinal mucosal barrier. Research into the association of the intestinal microbiota with health and disease (including diet, nutrition, obesity, inflammatory bowel disease, and cancer) continues to expand, with the field advancing at a rapid rate. Intestinal stem cells (ISCs) are the fundamental component of the mucosal barrier; they undergo continuous proliferation to replace the epithelium, which is also intimately involved in intestinal diseases. The intestinal microbiota, such as Lactobacillus, communicates with ISCs both directly and indirectly to regulate the proliferation and differentiation of ISCs. Moreover, Salmonella infection significantly decreased the expression of intestinal stem cell markers Lgr5 and Bmi1. However, the detailed interaction of intestinal microbiota and ISCs are still unclear. This review considers the progress of research on the model and niches of ISCs, as well as the complex interplay between the gut microbiota and ISCs, which will be crucial for explaining the mechanisms of intestinal diseases related to imbalances in the intestinal microbiota and ISCs.

The study demonstrates that colitis improvement is controlled by Lactobacillus ATCC 4356 by regulation of the Notch pathway; this finding will be useful for prevention against animal S. typhimurium infection.

PurposeThe aim of this article is to investigate the significance of pretreatment prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and their combination in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT).Materials and methodsA total of 585 patients were included. PNI and SII were calculated within 2 weeks prior to treatment. The optimal cutoff points were determined based on receiver operating characteristics curve analysis. The correlation between variables was analyzed. Kaplan–Meier method and Cox proportional hazards model were performed to evaluate the impact of both indices on overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). Further propensity score matching (PSM) was carried out to minimize the effects of confounders.ResultsThe optimal cutoff point of 53.0 for PNI and 527.20 for SII were selected. Pearson correlation coefficient showed an inverse correlation between PNI and SII (r = −0.232, P < 0.001). Multivariate analysis demonstrated that pretreatment PNI was an independent prognostic factor for OS (P = 0.047) and DMFS (P = 0.002) while pretreatment SII was an independent prognostic factor for OS (P = 0.003), PFS (P = 0.002), and DMFS (P = 0.002). After PSM, both parameters remained as independent prognosticators of survival. Additional prognostic value was observed in the combined use of PNI and SII.ConclusionPretreatment PNI and SII are promising indicators of survival in NPC patients undergoing IMRT. They can be utilized to refine current TNM staging system in predicting prognosis and developing an individualized treatment in these patients.

PurposeIn this study, we evaluated the prognostic values of hematological biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving definitive intensity-modulated radiotherapy (IMRT).MethodsThere were 427 NPC patients enrolled between January 2010 and March 2013 at Fudan University Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The Kaplan–Meier method and log-rank test were utilized to calculate progression-free survival (PFS) and overall survival (OS). The Cox proportional hazard models were applied to assess variables.ResultsANC, APC and ALC were declined, while NLR and PLR were elevated significantly after therapy (P < 0.001 each). On multivariate analysis, pre-treatment NLR ≥ 2.32 was associated with shortened OS (P = 0.048) and PFS (P = 0.008), whereas PLR ≥ 123.0 was related with inferior OS (P = 0.032), yet it was not correlated with PFS (P = 0.161).ConclusionsHigh pre-treatment NLR and PLR indicated poor survival in NPC patients treated with IMRT-based therapy. As easily accessible and economically feasible biomarkers, NLR and PLR can be applied into clinical practice, in combination with current TNM staging, to design a more personalized treatment in these patients.

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15–75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Results: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83–97.5%], 75.2% (95% CI: 61.5–84.0%) and 44.7% (95% CI: 32.3–57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7–59.0%) and 98.5% (95% CI: 91.7–100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0–20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0–97.5%) and 82.3% (95% CI: 70–90.4%), respectively. The most common adverse events of grades 3–4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. Conclusion: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016)

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