Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

PLK1 protects intestinal barrier function in sepsis: A translational research.

BACKGROUND: Sepsis and its related complications are very challenging in the intensive care unit, among which intestinal barrier injury is a general manifestation. Polo-like kinase 1 (PLK1) is widely studied in cancer, while its role in sepsis is poorly understood. In this study, the efficiency of PLK1 as a marker of intestinal barrier function as well as a predictor of mortality in sepsis was evaluated. METHODS: The level of serum PLK1 was measured in septic patients (n = 51) and controls (n = 20); subsequently, its correlation with serum diamine oxidase (DAO), d-lactate, and endotoxin levels and its ability topredict mortality were analysed. The survival rate and barrier injury degree were also assessed in septic mice. RESULTS: Serum PLK1 levels were elevated in septic patients, were negatively correlated with serum DAO, d-lactate, and endotoxin levels, and had a high predictive value for 28-day mortality in patients. The serum PLK1 level in non-survivors was lower. The expression of PLK1 in the intestine was decreased in septic mice, and overexpression or inhibition of PLK1 alleviated or aggravated intestinal barrier injury, respectively, as evaluated by Chiu's score, serum levels of DAO and d-lactate, and expression of tight junction proteins. Overexpressing PLK1 also decreased the 72-hour death rate of septic mice. Further study also revealed the negative correlation of PLK1 and IL-6 in patients, and increasing or interfering with PLK1 expression reduced or increased the serum IL-6 level in mice. CONCLUSIONS: PLK1 plays a critical role in intestinal barrier function during sepsis, providing a novel perspective for sepsis therapy in the clinic.

Lactobacillus johnsonii alleviates colitis by TLR1/2-STAT3 mediated CD206+ macrophagesIL-10 activation.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10-/- mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL-10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL-10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

HOXC10 indicates poor survival outcome in gastric cancer and promotes G1/S cell cycle transition through transcriptional repression of p21.

Homeobox (HOX) genes encode proteins that function as transcription factors during embryogenesis and tumorigenesis. We have previously reported upregulation of HOXC10 in gastric cancer (GC) tissues using cDNA microarray analysis. Though the functional role of HOXC10 in GC has been briefly reported, its specific mechanism is not fully understood. We analyzed the expression of HOXC10 in GC tissues, as well as its correlation with the survival outcome. By in vitro and in vivo assays, we further investigated the role of HOXC10 on cell cycle control and proliferation. Finally, we screened potential downstream targets of HOXC10 by cDNA microarray and explored the role of HOXC10 in p21 transcriptional repression through a dual luciferase reporter and chromatin immunoprecipitation. We illustrated the upregulation of HOXC10 in GC tissues and high HOXC10 expression related to poor survival outcome. Multivariable COX regression analysis showed that HOXC10 was an independent predictor of survival (HR=1.863; 95% CI: 1.076-3.225). Functionally, HOXC10 could promote GC cell proliferation and tumor growth in nude mice. Overexpression of HOXC10 accelerated G1/S cell cycle transition, whereas knocking down HOXC10 induced cell cycle arrest at the G1 phase. Critical factors of G1/S cell cycle transition including p21, CDK2, and c-Myc, were regulated by HOXC10. Importantly, an inverse correlation between p21 and HOXC10 expression in GC cell lines and tissues was observed. HOXC10 could directly bind to the promoter region of p21 and repress its transcriptional activity. Collectively, we identified HOXC10 as a predictor of poor prognosis in GC patients, and a novel transcriptional regulator of p21 in the G1/S cell cycle transition.

[A prenatal ultrasound study of cerebral sulci and gyrus development in fetuses with tetralogy of Fallot].

OBJECTIVE: To evaluate the development of the cerebral sulci and gyrus and cerebral blood flow in fetuses with tetralogy of Fallot (ToF) in the second and third trimesters using ultrasound imaging. METHODS: Forty fetuses (23-33+6 weeks) with ToF diagnosed using ultrasound imaging between December, 2015 and September, 2016 were analyzed in this study. The development of the cerebral sulci and gyrus was evaluated by measuring the parietal-occipital fissure (POF) depth, POF angle, sylvian fissure (SF) depth, SF width, uncovered insular width, calcarine fissure (CF) depth, hemisphere depth on the views of POF, SF and CF, uncovered insular ratio, biparietal diameter (BPD), and head circumference (HC). Cerebral hemodynamics were assessed by measuring the umbilical artery resistance index, umbilical artery pulsation index, middle cerebral artery pulsation index (MCA-PI), middle cerebral artery resistance index, the cerebral-to-placental resistance ratio, and the cerebroplacental ratio. RESULTS: In ToF fetuses, the POF depth, SF depth, CF depth, BPD, HC and hemisphere depth on the views of parietal-occipital sulcus and calcarine sulcus were significantly smaller than those in the control group (P<0.05). The middle cerebral artery resistance index, middle cerebral artery pulsation index, the cerebral-to-placental resistance ratio and the cerebroplacental ratio were also significantly lower in ToF fetuses than in the control group (P<0.05). CONCLUSION: The cerebral sulci and gyrus in ToF fetuses in second and third trimesters show underdevelopment compared with those in normal fetuses, and the changes in hemodynamics caused by abnormal cardiac structure might be one of the reasons for cerebral sulci and gyrus underdevelopment in fetuses with ToF.

Ultrasonographic Characteristics of Cortical Sulcus Development in the Human Fetus between 18 and 41 Weeks of Gestation.

BACKGROUND: Fetal brain development is a complicated process that continues throughout pregnancy. Fetal sulcus development has typical morphological features. Assessment of fetal sulcus development to understand the cortical maturation and development by prenatal ultrasound has become widespread. This study aimed to explore a reliable method to assess cortical sulcus and to describe the normal sonographic features of cortical sulcus development in the human fetus between 18 and 41 weeks of gestation. METHODS: A cross-sectional study was designed to examine the fetal cortical sulcus development at 18-41 weeks of gestation. Ultrasound was used to examine the insula, sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). Bland-Altman plots were used for assessing the concordance, and the intraclass correlation coefficient was used for assessing the reliability. RESULTS: SF images were successfully obtained in 100% of participants at 22 weeks of gestation, while the POF images and CF images could be obtained in 100% at 23 weeks of gestation and 24 weeks of gestation, respectively. The SF width, temporal lobe depth, POF depth, and the CF depth increased with the developed gestation. The width of uncovered insula and the POF angle decreased with the developed gestation. By 23 weeks of gestation, the insula was beginning to be covered. Moreover, it completed at 35 weeks of gestation. The intra- and inter-observer agreements showed consistent reproducibility. CONCLUSIONS: This study defined standard views of the fetal sulcus as well as the normal reference ranges of these sulcus measurements between 18 and 41 weeks of gestation. Such ultrasonographic measurements could be used to identify fetuses at risk of fetal neurological structural disorders.

[Examination of infant bone status with quantitative ultrasound at birth].

OBJECTIVE: Quantitative ultrasound (QUS) is a new method of evaluating Children's bone status, including bone mineral density and bone strength. The bone nutrition during fetal and early neonatal period is very important for the human bone development of whole life. The objective of this study was to evaluate the clinical application of QUS for newborn infants and to obtain the QUS data for normal neonates including premature infants. METHODS: An ultrasound bone sonometer, Omnisense, produced by Sunlight company of Israel, was applied to measure the bone speed of sound (SOS) of tibia in 157 neonates including 68 premature infants in the first week of life. RESULTS: (1) No significant difference in SOS was found between male (n = 88, SOS = 2968 +/- 115 m/s) and female infants (n = 69, SOS = 2956 +/- 105 m/s) (P = 0.524). The SOS of premature infants (n = 68, mean gestational age 33.0 +/- 2.5 weeks) and full-term infants (n = 89, mean gestational age of 39.4 +/- 1.3 weeks) were 2935 +/- 96 m/s and 2984 +/- 116 m/s, respectively, at birth and there was significant difference between them (P = 0.005). (2) There were significant differences of SOS in neonates who were born in different seasons (F = 4.377, P = 0.005); the significant difference remained (F = 3.933, P = 0.010) after the influences of gestational age and birth weight were eliminated. The SOS in neonates born in spring (March, April and May) and summer (June, July and August) were significantly lower than that of those born in autumn (September, October and November) and winter (December, January and February). The SOS in neonates born in summer was about 2.3% (75/2999) was lower than that of those born in winter. (3) Significant difference of SOS was observed between neonates with different birth weight [< 1500 g (n = 11), SOS = 2968 +/- 115 m/s; and > 2500 g (n = 86), SOS = 2980 +/- 113 m/s; P = 0.042]. (4) Significant correlations were found between SOS and gestational age (r = 0.270, P = 0.005), and between bone SOS and birth weight (r = 0.232, P = 0.015) in appropriate for gestational age (AGA) infants (n = 109); however, no such significant correlations were found in small for gestational age (SGA) infants or large for gestational age (LGA) infants. Multiple regression analysis showed that gestational age and the birth season were two important factors which may contribute to bone SOS of neonates at birth (n = 157, F = 8.515, P < 0.001, adjusted R(2) = 0.141), when the analysis was carried out with SOS as dependent variable and gestational age, birth weight, chronological age, calf length and the birth season as independent variables. CONCLUSION: QUS is a new method which is suitable for evaluating the bone status of neonates and it is free of radiation, non-invasive, the machine is portable and easy to manipulate at infant bed side. The present study suggests the need for particular care for the bone status in premature infants and supplement of vitamin D in pregnant women.