Non-Coding RNAs in Colorectal Cancer: Their Functions and Mechanisms.

Colorectal cancer (CRC) is a common malignancy with high mortality. However, the molecular mechanisms underlying CRC remain unclear. Controversies over the exact functions of non-coding RNAs (ncRNAs) in the progression of CRC have been prevailing for multiple years. Recently, accumulating evidence has demonstrated the regulatory roles of ncRNAs in various human cancers, including CRC. The intracellular signaling pathways by which ncRNAs act on tumor cells have been explored, and in CRC, various studies have identified numerous dysregulated ncRNAs that serve as oncogenes or tumor suppressors in the process of tumorigenesis through diverse mechanisms. In this review, we have summarized the functions and mechanisms of ncRNAs (mainly lncRNAs, miRNAs, and circRNAs) in the tumorigenesis of CRC. We also discuss the potential applications of ncRNAs as diagnostic and prognostic tools, as well as therapeutic targets in CRC. This review details strategies that trigger the recognition of CRC-related ncRNAs, as well as the methodologies and challenges of studying these molecules, and the forthcoming clinical applications of these findings.

Timing of Splenectomy after Acute Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition. Splenectomy may play a protective role in the development of SCI. However, little is known about whether the timing of splenectomy affects the outcome after SCI. Investigation into splenectomy after SCI would provide insight into how the timing can be selected following SCI to improve neurologic outcomes. Rats were randomized into a sham group, a nonsplenectomized group (NonSPX), four splenectomized groups with the surgery performed immediately, 6 h, 12 h, and 24 h after SCI (SPX0, SPX6, SPX12, and SPX24, respectively). Rats were subjected to severe contusive SCI at the level of the third thoracic vertebra. At different time points following SCI, Basso, Beattie, and Bresnahan (BBB) score was used to assess the recovery of injury. The animals in each group were randomly selected for tissue collection at days 3, 14, and 28 after surgery. Then, immunohistochemistry of immunologic cells was performed and inflammatory mediators were determined. Our study showed that splenectomy within 6 h after SCI improved BBB scores as compared with splenectomy more than 12 h after SCI, and decrease the immune cell responses to SCI. Protein levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were significantly elevated in nonsplenectomized group compared with sham group. No difference was observed in IL-10 at the lesion site between splenectomized and nonsplenectomized groups at 3 d post-SCI. The study demonstrates that splenectomy within 6 h after SCI would lessen the development of SCI and improve outcome.

Neuropeptide changes in an improved migraine model with repeat stimulations.

Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

OBJECTIVE: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). METHODS: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. RESULTS: We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-ß (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. CONCLUSIONS: Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. CLINICALTRIALSGOV IDENTIFIER: NCT03218293. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Serum long non-coding RNA LINC00887 as a potential biomarker for diagnosis of renal cell carcinoma.

The identification of non-invasive biomarkers for the detection of renal cell carcinoma (RCC) in early-stage patients may help improve disease outcome. Certain long non-coding RNAs (lncRNAs) have been reported to be possible biomarkers for the diagnosis and prognosis of cancer. Here, we examined the suitability of the lncRNA LINC00887 as a potential biomarker for RCC because its expression has been shown to be elevated in RCC tissue versus normal tissue in the Gene Expression Profiling Interactive Analysis (GEPIA) database. We found that LINC00887 expression is significantly increased in early-stage RCC tissues and the serum of early-stage RCC patients compared to matched normal tissues and the serum of healthy subjects, respectively. We also demonstrated that elevated serum LINC00887 is generated from the tumor tissues of RCC patients. Moreover, a receiver operating characteristic (ROC) curve was generated to analyze the diagnostic value of serum LINC00887. The area under the ROC cure differentiating early-stage RCC patients from healthy subjects was 0.8001, with a sensitivity of 71.05% and a specificity of 89.87%. Furthermore, we found that LINC00887 promotes RCC cell proliferation in vitro. Taken together, our findings suggest that a serum LINC00887 signature is associated with RCC cell proliferation and may be a potential biomarker for the detection of early-stage RCC.

Prognostic Potential of Electrocardiographic Parameters in Patients with Multiple Myeloma: A Retrospective Analysis of the Multiple Myeloma Population.

INTRODUCTION: Patients with multiple myeloma (MM) can develop cardiac abnormalities, predisposing them to the development of heart failure, arrhythmias, or infarction with poor prognosis. The purpose of this study is to evaluate the prognostic potential of electrocardiographic (ECG) parameters in patients with MM. METHODS: This study retrospectively included patients with MM from January 2010 to December 2018 in the First Affiliated Hospital of Xi'an Jiao Tong University. Univariate and multivariate Cox proportional hazard models were conducted to evaluate the relationship between ECG parameters and all-cause mortality in patients with MM. RESULTS: A total of 409 patients were included (mean age 61.3 ± 9.7 years, 59.2% male). The relationship between ECG parameters (including PR interval, voltage, QRS axis, QRS duration, and QTc interval) and all-cause mortality in patients with MM was evaluated. Overall, patients with QTc interval ≥ 400 ms have a significantly higher all-cause mortality compared to those with QTc interval < 400 ms (P < 0.001). When stratified by the International Staging System (ISS), this relationship was true for stages II and III (P < 0.01), but not stage I (P > 0.05). Patients with MM and QRS duration ≥ 120 ms had a higher all-cause mortality compared to those with QRS duration < 120 ms for women (P < 0.01) but not for men (P > 0.05). PR interval, voltage, and QRS axis did not predict mortality. CONCLUSION: QTc interval was independently associated with all-cause mortality in patients with MM, especially when QTc interval was more than 400 ms in more advanced stages II and III. ECG parameters may provide prognostic potential in patients with MM and aid risk stratification of these patients.

Cellular Inflammatory Response of the Spleen After Acute Spinal Cord Injury in Rat.

Spinal cord injury (SCI) involves both primary and secondary damages. After the phase of primary injury, a series of inflammatory responses initiate, which belong to the secondary injury. There has been little investigation into the cellular inflammatory response of the spleen to SCI. To disclose the impact of SCI on the spleen, we examined the inflammatory reactions of the spleen during the acute phase of SCI in rat. Adult rats were used as experimental animals and divided into un-injured, sham, and SCI groups (n = 36). Contusion injuries were produced at the T3 vertebral level. Spinal cords were harvested 6 h, 24 h, 48 h, 72 h, 120 h, and 168 h after surgery and were prepared for immunohistochemistry. Spleen wet weight was measured. Blood and spleens were prepared for quantitative analyses. The spleen index was significantly decreased in the SCI groups. Immunohistochemical results showed an increase of the infiltrating cells in the spinal cord tissues from SCI rats at all time points, peaking in 72 h post injury. In the blood, T and B lymphocytes significantly decreased in the SCI group as compared with the sham group, while monocyte increased. Surprisingly, in the SCI group, neutrophil initially decreased and subsequently tended to return toward baseline levels, then remained elevated until the end of the study. Spleen analyses revealed a significant increase in monocyte and neutrophil but a minor (not statistically significant) reduction in T and B lymphocytes. Our data show that the four most prevalent inflammatory cells infiltrate the spinal cord after injury. Increased levels of inflammatory cells (monocyte and neutrophil) in the blood and spleen appear to be very sensitive to SCI. The spleen plays a critical role in the acute phase of SCI.

CCAAT/Enhancer-Binding Protein ß Mediates the Killing of Toxoplasma gondii by Inducing Autophagy in Nonhematopoietic Cells.

Autophagy is a main defense strategy by which infected host cells can virtually induce the killing of parasite, including Toxoplasma gondii. However, the regulatory mechanisms of autophagy in T. gondii-infected nonhematopoietic cells are still unknown. Emerging evidence indicates that CCAAT/enhancer-binding protein ß (C/EBP ß) is associated with the regulation of autophagy. Herein, we hypothesized that C/EBP ß plays roles in inducing autophagy in nonhematopoietic cells. Expression of C/EBP ß was aberrantly regulated in endothelial cells and retinal pigment epithelial cells challenged by T. gondii. Inhibition of C/EBP ß reduced the killing of T. gondii in nonhematopoietic cells, whereas C/EBP ß overexpression resulted in the enhancement of killing of T. gondii as well as the increase in autophagy in infected cells. Furthermore, the mammalian target of rapamycin (mTOR) activation was found to be reduced by C/EBP ß overexpression, but increased by C/EBP ß inhibition. The increase in T. gondii killing induced by C/EBP ß overexpression was blocked by the mTOR activator phosphatidic acid and was increased by the inhibitor AZD8055. In conclusion, we demonstrate that C/EBP ß expression is increased in nonhematopoietic cells infected by T. gondii, resulting in the activation of autophagy in host cells by inhibiting mTOR pathway.