Esophageal magnetic compression anastomosis in dogs.

BACKGROUND: Magnetic compression anastomosis (MCA) is a novel suture-free reconstruction of the digestive tract. It has been used in gastrointestinal anastomosis, jejunal anastomosis, cholangioenteric anastomosis and so on. The traditional operative outcomes of congenital esophageal atresia and benign esophageal stricture are poor, and there are too many complications postoperatively. AIM: To test MCA technology to reconstruct the esophagus in dogs, prior to studying the feasibility and safety of MCA in humans. METHODS: Thirty-six dogs were randomized into either the study or control group (n = 18 per group). The dogs in the study group were subjected to end-to-end esophageal anastomosis with the magnetic compression device, while those in the control group underwent hand-sewn anastomosis with 4-0 absorbable multifilament Vicryl. We used interrupted single-layer inverting sutures. The anastomosis time, gross appearance, weight and pathology of the anastomosis were evaluated at one month, three months and six months postoperatively. RESULTS: The anastomosis time of the MCA group was shorter than that of the hand-sewn group (7.5 ± 1.0 min vs 12.5 ± 1.8 min, P < 0.01). In the MCA group, X-ray examination was performed every day to locate the magnetic device in the esophagus before the magnetic device fell off from the esophagus. In the hand-sewn group, dogs did not undergo X-ray examination. One month after the surgeries, the mean weight of the dogs in the hand-sewn group had decreased more than that of the dogs in the MCA group (11.63 ± 0.71 kg vs 12.73 ± 0.80 kg, P < 0.05). At 3 mo and 6 mo after the operation, the dogs' weights were similar between the two groups (13.75 ± 0.84 kg vs 14.03 ± 0.82 kg, 14.93 ± 0.80 kg vs 15.44 ± 0.47 kg). The number of inflammatory cells in MCA group was lower than that in hand-sewn group on 1 mo after operation. CONCLUSION: MCA is an effective and safe method for esophageal reconstruction. The anastomosis time of the MCA group was less than that of the hand-sewn group. This study shows that MCA technology may be applied to human esophageal reconstruction, provided these favorable results are confirmed by more publications.

Long non-coding RNA RPL34-AS1 ameliorates oxygen-glucose deprivation-induced neuronal injury via modulating miR-223-3p/IGF1R axis.

Ribosomal protein L34-antisense RNA 1 (RPL34-AS1), one of the long non-coding RNAs (lncRNAs), plays an important function in regulating diverse human malignant tumors. Nevertheless, the functions of RPL34-AS1 in ischemic stroke remain unclear. The present work focused on determining the candidate targets of RPL34-AS1 and its related mechanism in ischemic injury. The oxygen-glucose deprivation (OGD/R) in vitro cell model and middle cerebral artery occlusion (MCAO) in vivo rat model were utilized to simulate the pathological process of ischemic stroke. Additionally, the CCK8, WB (detecting Bcl-2 and Bax protein levels), and caspase-3 activity assays were done to investigate the anti-apoptotic functions of RPL34-AS1. The relationship among RPL34-AS1, insulin-like growth factor 1 receptor (IGF1R), and microRNA-223-3p (miR-223-3p) was determined through luciferase reporter assay. In this study, RPL34-AS1 expression was reduced in patients suffering from ischemic stroke. The overexpression of RPL34-AS1 reduced ischemic brain damage. However, the cell viability and glucose uptake were increased, and the apoptosis rate was decreased in the OGD/R-induced neurons. Further, miR-223-3p resulted in the decreased cell viability and glucose uptake and the increased cell apoptosis to cause ischemic brain damage. Besides, the neuroprotective effects of RPL34-AS1 on OGD/R injury were partly reversed by miR-223-3p. Mechanistically, lncRNA RPL34-AS1 could function as the competing endogenous RNA (ceRNA) of miR-223-3p to regulate IGF1R. Collectively, our study demonstrated that lncRNA RPL34-AS1 attenuated OGD/R-induced neuronal injury by mediating miR-223-3p/IGF1R axis. This discovery might serve as the candidate therapeutic target for ischemic stroke.

Neuroprotective effects of methylcobalamin in cerebral ischemia/reperfusion injury through activation of the ERK1/2 signaling pathway.

Despite advances in the understanding of the pathophysiology of ischemic stroke, therapeutic options remain limited. Methylcobalamin is an endogenous vitamin B12 that exhibits anti-inflammatory and antiapoptotic activities in a variety of diseases. In this study, we aimed to explore the neuroprotective effects and mechanism of action of methylcobalamin on cerebral ischemic injury in vitro and in vivo. The oxygen and glucose deprivation/reperfusion model and middle cerebral artery occlusion model were used to simulate cerebral ischemic injury in vitro and in vivo. Cell viability, inflammatory factors, cell apoptosis, and protein expression levels were determined. Further, autophagy flux and the cerebral infarction volume were measured. The modified neurological severity score, Longa score, Rotarod assay, and foot-fault test were used to evaluate behavioral changes and neurological deficits in rats. In vitro, methylcobalamin significantly increased cell viability, decreased lactate dehydrogenase release, attenuated inflammatory cytokine expression, reduced the apoptotic proportion, and enhanced autophagy flux after OGD treatment. In addition, Bcl-2 and Beclin1 expression levels and the LC3 II/I ratio were increased, whereas levels of Bax and cleaved caspase-3 were decreased. In vivo, methylcobalamin significantly reduced the cerebral infarction volume and neurological deficits in the rats. Furthermore, methylcobalamin activated the ERK1/2 pathway, whereas ERK1/2 inhibitors diminished its effects in the in vitro and in vivo models. In conclusion, methylcobalamin may exert a neuroprotective effect on cerebral ischemia and is a promising drug candidate for developing novel neuroprotective therapies.

Long non-coding RNA MALAT1 regulates angiogenesis following oxygen-glucose deprivation/reoxygenation.

Long non-coding RNAs (lncRNAs) have been identified as playing critical roles in multiple diseases. However, little is known regarding their roles and mechanisms in post-stroke angiogenesis. Our studies focused on deciphering the functional roles and the underlying mechanisms of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the process of angiogenesis following oxygen-glucose deprivation/reoxygenation (OGD/R). We characterized the up-regulation of MALAT1 expression in the process of angiogenesis after hypoxic injury in vivo and in vitro. We further showed that compared with the empty vector, MALAT1 knockdown had significantly reduced the capacity for angiogenesis, which was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), scratching, cell cycle and immunofluorescent staining. Thus, our findings suggest that MALAT1 may mediate proangiogenic function in OGD/R. To further explore the potential mechanisms, we used lentiviruses expressing shMALAT1 and empty vector; the results revealed that shMALAT1 reduced the expression of 15-lipoxygenase 1 (15-LOX1), vascular endothelial growth factor (VEGF) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). Taken together, our results are the first to propose that MALAT1 may regulate angiogenesis through the 15-LOX1/STAT3 signalling pathway, and they may provide a critical target for the treatment of hypoxic injury and an avenue for therapeutic angiogenesis.

Discovering Proangiogenic Drugs in Ischemic Stroke Based on the Relationship between Protein Domain and Drug Substructure.

As an important protective mechanism against cerebral ischemia, angiogenesis has become a topic of interest in the treatment of ischemic stroke with the challenge that few drugs promote angiogenesis. Previous studies of the identification of drug-target interactions mainly focused on the overall structures of drugs and proteins, which limited the discovery of novel structure drugs. In this article, we proposed a new strategy for discovering proangiogenic drugs based on the assumption that drug-protein interaction is mediated by substructure and domain. First, we identified substructure-domain relationships according to the known drug-protein interactions and established the drug-substructure-domain-protein relationships of genes that are proangiogenic in brain tissue and expressed significantly during ischemic stroke. Then we quantified the intensity of interaction between each drug and each protein. Finally, we obtained 540 interactive relationships between 238 drugs and 54 genes, establishing a drug-gene network with two patterns of independent and complex drug-gene interactions. Both of the patterns facilitated finding not only drugs with the same overall structure but also drugs with a different overall structure based on the same or a similar protein spectrum. In addition, we analyzed the mechanism of action of each predicted drug and extracted drugs with similar mechanisms. In vitro, our results showed that azelnidipine, azilsartan, lercanidipine, nafcillin, and vortioxetine enhanced bEnd.3 cell proliferation, migration, tube formation, and the expression of angiogenic marker PCNA. Azelnidipine, azilsartan, lercanidipine, and nafcillin increased the level of expression of proangiogenic factor VEGF. Unlike previous studies focusing on the overall structures of drugs, our research highlighted local structural similarity, which has great potential in the search for more proangiogenic drugs with novel structures.

Fiber Bragg gratings inscribed using 800nm femtosecond laser and a phase mask in single- and multi-core mid-IR glass fibers.

For the first time, Fiber Bragg grating (FBG) structures have been inscribed in single-core passive germanate and three-core passive and active tellurite glass fibers using 800 nm femtosecond (fs) laser and phase mask technique. With fs peak power intensity in the order of 10(11)W/cm(2), the FBG spectra with 2nd and 3rd order resonances at 1540 and 1033 nm in the germanate glass fiber and 2nd order resonances at approximately 1694 and approximately 1677 nm with strengths up to 14 dB in all three cores in the tellurite fiber were observed. Thermal responsivities of the FBGs made in these mid-IR glass fibers were characterized, showing average temperature responsivity approximately 20 pm/ degrees C. Strain responsivities of the FBGs in germanate glass fiber were measured to be 1.219 pm/microepsilon.