Embryonic stem cells differentiate into cardiac myocytes, repeating in vitro the structural and molecular changes associated with cardiac development. Currently, it is not clear whether the electrophysiological properties of the multicellular cardiac structure follow cardiac maturation as well. In long-term recordings of extracellular field potentials with microelectrode arrays consisting of 60 substrate-integrated electrodes, we examined the electrophysiological properties during the ongoing differentiation process. The beating frequency of the growing preparations increased from 1 to 5 Hz concomitant to a decrease of the action potential duration and action potential rise time. A developmental increase of the conduction velocity could be attributed to an increased expression of connexin43 gap junction channels. Whereas isoprenalin elicited a positive chronotropic response from the first day of spontaneous beating onward, a concentration-dependent negative chronotropic effect of carbachol only developed after approximately 4 days. The in vitro development of the three-dimensional cardiac preparation thus closely follows the development described for the mouse embryonic heart, making it an ideal model to monitor the differentiation of electrical activity in embryonic cardiomyocytes.

BackgroundThe cause of almost all cases of Parkinson’s disease (PD) remains unknown. Recent years have seen an explosion in the rate of discovery of genetic defects linked to PD. Different racial and geographical populations may have different distributions of genetic variants.MethodsIn the current study, we screened the following genetic variants, including some rare mutations and single nucleotide polymorphisms (SNPs), in a pedigree and cases-controls. To best of our knowledge, we first screened these variants known to be associated with neurodegeneration disease, E46K (rs104893875) in SNCA, A1442P in LRRK2, IVS9 in PARK2, A350V in SLC41A1, P268S (rs2066842), R702W (rs2066844), G908R (rs2066845), 1007fs (rs2066847) in NOD2 and G2385R (rs34778348) in LRRK2 from southern China population. Genotyping was performed by jointly using primers overlapping polymerase chain reaction (PCR) site-directed mutagenesis, restriction fragment length polymorphism (RFLP), and capillary electrophoresis (CE).ResultsWe didn’t discover above 9 variants in the family members of the pedigree. Furthermore, of 237 patients with sporadic Parkinson’s disease and 190 controls, no heterozygosity or homozygosity were found from E46K, A1442P, A350V, R702W, G908R, or 1007fs but heterozygosity onto G2385R, IVS9, and P268S. No significant difference between cases and controls was found in both allele frequency (P = 0.572) and genotype frequency (P = 0.348) of IVS9. However, significant differences in genotype frequency (P = 0.009) of G2385R were consistent with prior observation. Eight patients with Parkinson’s disease (2 women and 6 men are over the age of 50 years at onset of PD) carried the P268S heterozygous variation in NOD2. There was no heterozygosity or homozygosity of P268S in the controls. Genotype frequency of P268S (P = 0.0450) had significant differences.ConclusionsOur results suggested that the P268S variant in NOD2 might be a risk factor for susceptibility to sporadic Parkinson’s disease in Chinese populations. It also implied that the inflammatory response may play a role in PD.

Metastasis has been one of the major reasons for cancer-related mortality, with multiple genes and pathways being involved in this complex process. Given the molecular variations underlying metastasis of hepatocellular carcinoma (HCC) remains largely unknown; in our previous work, we found copying number of protocadherin-17 (PCDH-17) was significantly deleted in HCC tissues that occurred to metastasize compared with that in the primary HCC without metastasis. Therefore, we hypothesized that PCDH-17 may suppress the metastasis of HCC. There has been, however, no relevant literature available regarding PCDH-17 in HCC. In the present study, we have immunohistochemically detected and clinicopathologically analyzed the expression of PCDH-17 in vivo in clinical tissues; besides, we have explored the role of PCDH-17 ex vivo using a panel of HCC cell lines. It was discovered that PCDH-17 expression was clinically correlated with overall prognosis as well as metastasis in vivo and that PCDH-17 inhibited metastasis via EGFR/MEK/ERK signaling pathway ex vivo. Together, our results obtained both in vivo and ex vivo suggested that activation of EGFR/MEK/ERK signaling pathway through PCDH-17 promotes metastasis in HCC.

(Abstracted from Ultrasound Obstet Gynecol 2020;55:96–104) Early pregnancy loss is most commonly caused by embryonic numerical and structural chromosomal abnormalities, which explain more than 50% of miscarriages. In more recent years, submicroscopic copy-number variations (CNVs) have also been identified in some early miscarriage specimens.

Background: Previous studies have showed that argonaute 2 is a potential factor related to genesis of several cancers, however, there have been no reports concerning gliomas. Methods: Paraffin specimens of 129 brain glioma cases were collected from a hospital affiliated to Binzhou Medical University from January 2008 to July 2013. We examined both argonaute 2 mRNA and protein expression by real-time quantitative PCR (qRT-PCR), Western blot analysis, and immunohistochemistry (IHC). The survival curves of the patients were determined using the Kaplan-Meier method and Cox regression, and the log-rank test was used for statistical evaluations. Results: Both argonaute 2 mRNA and protein were upregulated in high-grade when compared to low-grade tumor tissues. Multivariate analysis revealed that argonaute 2 protein expression was independently associated with the overall survival (HR=4.587, 95% CI: 3.001-6.993; P=0.002), and that argonaute 2 protein expression and WHO grading were independent prognostic factors for progression-free survival (HR=4.792, 95% CI: 3.993-5.672; P<0.001, and HR=2.109, 95% CI: 1.278-8.229; P=0.039, respectively). Kaplan-Meier analysis with the log-rank test indicated that high argonaute 2 protein expression had a significant impact on overall survival (P=0.0169) and progression-free survival (P=0.0324). Conclusions: The present study showed that argonaute 2 expression is up-regulated in gliomas. Argonaute 2 might also serve as a novel prognostic marker.

We aimed to investigate the relationship between the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the radiation tolerance of patients with head and neck squamous cell carcinoma (HNSCC). From January 2015 to January 2016, 117 patients with HNSCC were enrolled in our study and assigned into the sensitive and tolerance groups based on curative effect. Immunohistochemistry (IHC) was conducted to measure protein expressions of Nrf2, heme oxygenase-1 (HO1), NADPH quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST). Human squamous cell carcinoma cell line, HSC-4, was induced by radiation to construct the HSC-4-radiation resistance (RR) cell line. HSC-4 and HSC-4-RR were also assigned into the blank, negative control (NC) and Nrf2 siRNA groups. Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect cell viability, mRNA expression and protein expression, respectively, of Nrf2, HO1, NQO1 and GST. A total of 40 nude mice were equally assigned into the untreated, Nrf2 siRNA, radiation therapy (RT) and RT + Nrf2 siRNA groups. Compared with the sensitive group, patients in the tolerance group had upregulated Nrf2, HO1, NQO1 and GST expressions. HSC-4-RR cell line had improved cell viability and higher protein and mRNA expressions of Nrf2, HO1, NQO1 and GST compared with HSC-4 cell line. Compared with the HSC-4-NC and HSC-4-blank groups, the HSC-4-Nrf2 siRNA group had downregulated cell viability. Compared with the HSC-4-RR-NC and HSC-4-RR-blank groups, the HSC-4-RR-Nrf2 siRNA group had lower cell viability. However, the HSC-4-RR-Nrf2 siRNA group had elevated cell viability than the HSC-4-Nrf2 siRNA group. Tumor volume and tumor weight in the RT and RT + Nrf2 siRNA groups decreased evidently. The RT + Nrf2 siRNA group exhibited decreased tumor volume and tumor weight in comparison with the RT group. Our data demonstrated that downregulation of HO1, NQO1 and GST via inhibiting Nrf2 signaling pathway reduces the radiation tolerance of patients with HNSCC.

Lamivudine prophylaxis in HBsAg seropositive breast cancer patients undergoing chemotherapy is effective in reducing HBV reactivation and HBV-associated morbidity and mortality.

Three cases of transient proximal small bowel angioedema induced by intravenous administration of nonionic iodinated contrast media (CM) are presented. Computed tomography (CT) images in the venous phase displayed the proximal small bowel with circumferential thickening of the wall including the duodenum and proximal segment of the jejunum. The bowel wall was normal in non-enhanced images, and normal or inconspicuous in arterial phase enhanced images. In one of the three cases, the bowel wall was thickened in venous phase but disappeared in the 40 s delayed phase images. No filling defect was seen in the lumen of the superior mesenteric artery and vein. No peritoneal effusion or mesentery abnormality was found. Each of these patients reported only mild abdominal discomfort and recovered without specific treatment within a short time. Only one patient suffered mild diarrhea after scanning which had resolved by the following day. The transient anaphylactic small bowel angioedema due to intravenous iodinated contrast media was easily diagnosed based on its characteristic CT findings and clinical symptoms. Differential diagnosis may include inflammatory and ischemic bowel disease, as well as neoplasms. A three-phase CT protocol and good understanding of this disorder are fundamentally important in the diagnosis of this condition. The supposed etiology behind the transient anaphylactic reaction to intravenous administration of iodinated CM in small bowel is similar to other CM-induced hypersensitive immediate reactions. The predilection location of transient anaphylactic bowel angioedema is the small intestine, particularly the proximal segment. A speculated cause may be the richer supply of vessels in the small intestine, ample mucous folds and loose connective tissue in the duodenum and the jejunum.