Matrine reduces the secretion of exosomal circSLC7A6 from cancer-associated fibroblast to inhibit tumorigenesis of colorectal cancer by regulating CXCR5.

Tumor microenvironment (e.g., stromal cells) has been suggested to be implicated in colorectal cancer (CRC) progression. Of which, cancer-associated fibroblasts (CAFs) are believed as one of the key stromal cells in tumors. Traditionally, matrine was used to treat cancers, including CRC. Unfortunately, little is known about whether matrine inhibited CRC progression via CAFs. In this research, we analyzed cell proliferation, invasion and apoptosis by cell colony formation assay, transwell assay and Annexin V staining, respectively. circSLC7A6 and CXCR5 expression levels were examined by RT-qPCR. Exosomes were analyzed by NanoSight Tracking Analysis and exosome markers were probed by westernblot. In the results, we found that matrine significantly led to inhibited cell proliferation and invasion, and increased apoptosis. Moreover, matrine blocked circSLC7A6 exosome secretion from CAFs. circSLC7A6 acted as promoter for CRC cell proliferation and invasion, whereas as inhibitor for apoptosis. Clinically, circSLC7A6 was upregulated in CRC tumor tissues compared to adjacent normal tissues. In addition, circSLC7A6 was associated with higher overall survival. Eventually, we confirmed that chemokine receptor CXCR5 was a crucial effector for circSLC7A6-modulated tumorigenesis. Here, our data suggest matrine inhibits CRC tumorigenesis through blocking exosomal circSLC7A6 release from CAFs. This finding will provide strong evidence for treating CRC using matrine.

Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation.

BACKGROUND: NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which affected individuals show developmental delay, epilepsy, intellectual disability, abnormal liver function, and poor growth. This study presents a 10-month-old female infant with elevated liver transaminases, developmental delay, epilepsy (subclinical seizures), and constipation who possesses two compound heterozygous mutations in NGLY1. CASE PRESENTATION: The proband was admitted to the Department of Gastroenterology, Children's Hospital of Soochow University, with elevated liver transaminases. She had a history of intrauterine growth retardation and exhibited elevated transaminases, global developmental delay, seizures and light constipation during early infancy. Whole-exome sequencing (WES) and Sanger sequencing revealed two compound heterozygous mutations in NGLY1 that had been inherited in an autosomal recessive manner from her parents. One was a termination mutation, c.1168C > T (p.R390*), and the other was a missense mutation, c.1156G > T (p.D386Y). NGLY1-CDDG is a rare disorder, with a few dozen cases. The two mutations of this proband has not been previously identified. CONCLUSIONS: This study investigated a Chinese proband with NGLY1-CDDG born from healthy parents who was studied using WES and Sanger sequencing to identify the causative mutations. We identified two novel compound heterozygous mutations in NGLY1, c.1168C > T (p.R390*)/c.1156G > T (p.D386Y), which are probably causative of disease.

A meta-analysis of dietary carbohydrate intake and inflammatory bowel disease risk: evidence from 15 epidemiology studies.

BACKGROUND AND PURPOSE: epidemiological studies that assess the association of dietary total carbohydrate intake and inflammatory bowel disease risk (IBD) have yielded controversial results. Therefore, this study of various epidemiological studies was conducted in order to explore this relationship. METHODS: a systematic literature search of the PubMed, Embase, Web of Science and Medline databases was performed up to September 2017. Cohort, case-control or cross-sectional design studies were included that reported the association of dietary carbohydrate intake and IBD risk. Summary odds ratio (OR) and the corresponding 95% CI were calculated using the random effects model. RESULTS: a total of eight articles with 15 individual studies that included 1,361 cases were eligible according to the inclusion criteria. Dietary carbohydrate intake had a non-significant relationship with the risk of IBD (OR = 1.091, 95% CI = 0.817-1.455, I2 = 31.6%, pfor heterogeneity = 0.116). The pooled OR and 95% CI for ulcerative colitis (UC) and Crohn's disease (CD) with regard to dietary carbohydrate intake was 1.167 (0.777-1.752) and 1.010 (0.630-1.618), respectively. These associations were also non-significant in both European and Asia populations. CONCLUSIONS: a higher dietary total carbohydrate intake had a non-significant relationship with IBD risk. Further studies with large populations are needed to verify this relationship.

A novel splice donor mutation in DCLRE1C caused atypical severe combined immunodeficiency in a patient with colon lymphoma: case report and literature review.

Introduction: Hypomorphic mutations of DCLRE1C cause an atypical severe combined immunodeficiency (SCID), and Epstein-Barr virus (EBV)-related colon lymphoma is a rare complication. Case presentation: A teenage boy presented with colon EBV-related colon lymphoma, plantar warts, and a history of recurrent pneumonia. His peripheral blood lymphocyte count and serum level of immunoglobulin (Ig) G were normal, but he exhibited a T+B-NK+ immunophenotype. Genetic analysis by whole exome sequencing revealed compound heterozygous mutations of DCLRE1C (NM_001033855.3), including a novel paternal splicing donor mutation (c.109 + 2T>C) in intron 1, and a maternal c.1147C>T (p.R383X) nonsense mutation in exon 13. Based on his clinical features and genetic results, the diagnosis of atypical SCID with colon lymphoma was established. Our review shows that seven patients, including our patient, have been reported to develop lymphoma, all with hypomorphic DCLRE1C mutations. Among these cases, six had EBV-related B-cell lineage lymphoma, and one had Hodgkin lymphoma with EBV reactivation. Unfortunately, all of the patients died. Conclusion: Recognizing the radiosensitivity of the disease is critical for the prognosis. Hematopoietic stem cell transplantation before being infected with EBV is an optimal treatment.

[Research of chitins to technology of clarification for xiangjuganmaokeli extraction].

OBJECTIVE: To study the procedure of chitosan to technology of clarification for xiangjuganmaokeli extraction and measure its content. METHODS: The best technology was choosed by orthogonal test. Relative density, the total solid, total sugar and the content of acacetin were examined after the nature clearness and chitins clarify. The total sugar was Counte-racted with ether siank, hydrolyzed with the phenol and sulfuric acid and examined in the 490 nm. Acaciin in powdered herb was determined by HPLC method. RESULTS: The chitin clarifies in front and back relative density, the total solid, the total sugar slightly descends, but the acacetin did not show the significant difference. CONCLUSION: Chitins to technology of clarification for xiangjuganmaokeli extraction can attain the clearness result, and the acacetin did not show the significant difference in front and back.