The currently used biomarkers for acute myocardial infarction (AMI) are blood creatinine phosphokinase-muscle band (CPK-MB), troponin-T (TnT), and troponin I (TnI). However, no good biomarkers are identified in urine after AMI, because these blood protein biomarkers are difficult to be filtered into urine. In this study, the role of urine microRNAs in the diagnosis of AMI and the mechanism involved were determined. We found that urine miR-1 was quickly increased in rats after AMI with peak at 24 h after AMI, in which an over 50-fold increase was demonstrated. At 7 days after AMI, the urine miR-1 level was returned to the basal level. No miR-208 was found in normal urine. In urine from rats with AMI, miR-208 was easily detected. To determine the mechanism involved, we determined the levels of heart-released miR-1 in the liver, spleen and kidney after AMI in rats and found that the kidney was an important metabolic organ. To determine the renal elimination of blood miRNAs, we isolated serum exosomes from rats after AMI and injected these exosomes into the circulating blood of normal rats. We found that the urine miR-1 was significantly increased in exosome-injected animals. Moreover, PKH67-labeled exosomes injected into circulating blood could enter into the kidney tissues and cells, as well as urine. Furthermore, the levels of urine miR-1 were significantly increased in patients with AMI. The results suggest that urine miRNAs such as miR-1 could be novel urine biomarkers for AMI.

No abstract

Cholangiocarcinoma (CCA) is a primary malignancy, which is often diagnosed as locally advanced or metastatic. Previous studies have revealed genomic characteristics of CCA in Western patients, however comprehensive genomic features of CCA in Chinese patients have not been well understood. To explore the specific genomic characteristics of Chinese patients with CCA, a total of 66 patients with CCA, including 44 intrahepatic CCA (iCCA) and 22 extrahepatic CCA (exCCA) cases, were studied. The most commonly altered genes in CCAs were TP53 (62.12%, 41/66), KRAS (36.36%, 24/66), SMAD4 (24.24%, 16/66), TERT (21.21%, 14/66), ARID1A (19.70%, 13/66), CDKN2A (19.70%, 13/66), KMT2C (9.09%, 6/66) and RBM10 (9.09%, 6/66), ERBB2 (7.58%, 5/66) and BRAF (7.58%, 5/66). Many gene mutations, including STK11, CCND1 and FGF19, were only found in iCCA. RBM10 mutations were found to be significantly higher in exCCA. The gene mutations of neurofibromin 1, STK11, CCND1 and FBXW7 specifically occurred in males, whereas gene mutations of ERBB2, AXIN2 and CREBBP specifically occurred in females. ERBB2 mutations were significantly associated with the sex of patients with CCA. Mutations in PIK3CA, FGFR2 and ZNF750 were significantly associated with the age of patients with CCA and TERT mutations were significantly associated with tumor differentiation. Alterations in KMT2C, PBRM1, AXIN2, MAGI2, BRCA2 and SPTA1 were associated with tumor mutational burden. The findings of the present study suggest that targeted sequencing, using next-generation sequencing technology, provides comprehensive and accurate information on genomic alterations, which will provide novel potential biomarkers for the diagnosis of CCA and may guide precise therapeutic strategies for Chinese patients with CCA.

BACKGROUND: Sophora alopecuroides alkaloids are the main constituents for the broad bioactivities on insect pests, especially on aphids. However, the aphicidal mode of action of S. alopecuroides alkaloids remains unclear. To clarify the aphicidal action, avermectin was selected as a positive control, and matrine, sophocarpine were chosen as the representative alkaloids to determine the physiological and biochemical effects on pea aphids (Acyrthosiphon pisum). RESULTS: The aphids treated by matrine and sophocarpine developed the intoxication symptoms of convulsions, paralysis, and death. However, avermectin showed no convulsions. Moreover, the two alkaloids had a significant inducing effect on glutamic acid decarboxylase, and the specific enzyme activity was 1.14-1.22 times of the control group. In the meanwhile, both matrine and sophocarpine possessed a dose-response and time-response inhibitory effect on alanine aminotransferase in vivo and in vitro. Furthermore, the glutamate content in pea aphids treated with the two alkaloids increased significantly with time, which was about 1.5-2.0 times that of the control group. Similarly, the GABA content elevated significantly, with an increase of 1.0-1.3 times. In addition, all the treatments, except avermectin, presented inhibitory effects on Na + , K +-ATPase, Ca 2+ and Mg 2 +-ATPase, with dose-response and time-response effect. However, the three treatments had no significant effect on acetylcholinesterase and acetylcholine content. CONCLUSION: The toxicological action of matrine and sophocarpine is related to the regulation on glutamate and γ-aminobutyric acid systems and has certain similarities to that of avermectin. These findings would provide a basis for further mechanism elucidation.

All of the patients underwent pre-operative imaging before surgery, and intra-operative endoscopic detection was selectively used for large, deep tumors. Complete resection of the tumor was used in 158 patients (95%), with a transcervical surgical approach applied in 144 cases (84%). Of 167 tumors, 150 (90%) were benign and 17 (10%) were malignant, with neurilemmoma/schwannoma as the most frequent pathology (42%). Surgical complications were reported in 26 patients (15%), most commonly unilateral paralysis of the vocal cords (6%). Two patients (1%) presented with recurrence, on average 2.5 years (range = 1-4 years) after initial excision, and the mean follow-up time was 3.8 years (range = 10 months-10 years).

Background: We report functional and clinical data uncovering the significance of B-cell lymphoma/leukemia 11A (BCL11A) in laryngeal squamous cell carcinoma (LSCC). Methods: We examined BCL11A expression in a cohort of LSCC patients and evaluated the association between BCL11A expression and clinicopathological features. We investigated the consequences of overexpressing BCL11A in the LSCC cell line on proliferation, migration, invasion, cell cycle, chemosensitivity, and growth in vivo. We explored the relationship between BCL11A and MDM2 in LSCC and tumorigenesis pathways by using the Human Cancer PathwayFinder Array. Results: High levels of BCL11A were found in LSCC tissues and were more frequently associated with advanced lymphatic metastasis stages with poor prognoses. BCL11A overexpression enhanced LSCC proliferation in vitro and vivo. A positive correlation between MDM2 and BCL11A expression was identified. Conclusions: These data uncover important functions of BCL11A in LSCC and identify BCL11A as a prognostic biomarker and potential therapeutic target in LSCC.

This study investigated the effects of supplementing sow diets with lysozyme during the late gestation to lactation stage on the performance of sows and their offspring. Sixty sows (Yorkshire × Landrace, 3 to 6 of parity) at day 85 of gestation were allocated to the following 3 dietary treatments: 1) sows fed a basal diet from late gestation to lactation (control, n = 20), 2) sows fed a basal diet with lysozyme 150 g/t (LZM 150, n = 20), and 3) sows fed a basal diet with lysozyme 300 g/t (LZM 300, n = 20). During the lactation period, sows fed diets containing lysozyme had increased average daily feed intake (ADFI) (P < 0.01) and decreased weaning-to-estrus interval (WEI, P < 0.05), but there were no significant effects on backfat during the trial among treatments. Sows fed lysozyme diets had increased (P < 0.05) serum concentration of total protein (TP) compared with those fed the control diets. Serum immunoglobulin M (IgM) of the sows increased (P < 0.05) on day 1 of lactation, immunoglobulin A (IgA) and interleukin-10 (IL-10) increased (P < 0.05) on day 7 of lactation, and immunoglobulin G (IgG) had a tendency to increase (P = 0.05) during the lactation. Milk concentration of IgA increased (P < 0.05) on day 1 and 7 of lactation and tended to be greater (P = 0.06) on day 21 of lactation. No significant differences among the dietary treatments were observed in placental tissue mRNA expression of interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), polymeric immunoglobulin receptor (pIgR), or the concentrations of IL-6, IL-10, TNF-α, or secretory immunoglobulin A (sIgA). Moreover, there was a decrease (P < 0.05) in stillborn in sows fed lysozyme diets. The diarrhea rate decreased (P < 0.05) and serum concentrations of IgA, IgG, IgM, and IL-10 increased (P < 0.05) in piglets from sows fed the diets containing lysozyme compared with piglets from sows fed the control diet. The serum concentrations of TP increased (P < 0.05), and albumin (ALB) and globulin (GLB) had a tendency to increase (P = 0.08, P = 0.06) in piglets from sows fed the diets containing lysozyme compared with piglets from sows fed the control diet. In conclusion, this study indicates that feeding sows diets supplemented with lysozyme from the late gestation through lactation stage increased sow ADFI during the lactation, shortened the WEI, and improved the maternal and offspring health status as indicated by immunological characteristics and a reduced incidence of diarrhea in piglets.

Compared with the controls, the LSCC group had significantly higher frequencies of L-allele (> 29 repeats) and L-allele carriers (p < 0.001, OR = 2.037 and p = 0.005, OR = 2.152, respectively). The frequencies of lymph node metastasis and of moderate or poor differentiation were significantly higher in L-allele carriers compared to non-L-allele carriers (p < 0.05). Significantly lower serum HO-1 levels were detected in LSCC patients (p < 0.001), and patients with lower serum HO-1 levels had more advanced cancer stage and a higher lymph node metastasis rate (p < 0.05). Furthermore, the L-allele carriers had lower serum HO-1 concentrations compared with the non-L-allele carriers (p = 0.019).