Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Development of lignocellulosic biorefineries for the sustainable production of biofuels: Towards circular bioeconomy.

The idea of environment friendly and affordable renewable energy resources has prompted the industry to focus on the set up of biorefineries for sustainable bioeconomy. Lignocellulosic biomass (LCB) is considered as an abundantly available renewable feedstock for the production of biofuels which can potentially reduce the dependence on petrochemical refineries. By utilizing various conversion technologies, an integrated biorefinery platform of LCB can be created, embracing the idea of the 'circular bioeconomy'. The development of effective pretreatment methods and biocatalytic systems by various bioengineering and machine learning approaches could reduce the bioprocessing costs, thereby making biomass-based biorefinery more sustainable. This review summarizes the development and advances in the lignocellulosic biorefineries from the LCB to the final product stage using various different state-of-the-art approaches for the progress of circular bioeconomy. The life cycle assessment which generates knowledge on the environmental impacts related to biofuel production chains is also summarized.

New NNN pincer copper complexes as potential anti-prostate cancer agents.

Eleven novel NNN Cu(II) complexes supported by a tridentate bis(imidazo[1,2-α]pyridin-2-yl)pyridine ligand were synthesized and characterized by elemental analysis, HRMS, and X-ray determination. Target prediction and docking studies indicated that these pincer complexes formed hydrogen bonds with Asp33 and Gly35 of Cathepsin D protein, which is highly associated with prognosis of advanced prostate cancer. Furthermore, they exhibited anti-proliferation activity in both androgen-sensitive and androgen-insensitive prostate cancer cells according to WST-1 assay results. Mechanistic study showed that pincer complexes arrested cell cycle progression at G0/G1 phase and inhibited Cathepsin D regulated signaling pathways. Most importantly, new pincer copper complexes significantly inhibited xenograft prostate cancer growth along with a promising in vivo safety profile. In summary, these results suggest the applicability of the developed novel pincer copper complexes as promising anticancer agents for prostate cancer treatment.

The Novel Function of Unsymmetrical Chiral CCN Pincer Nickel Complexes as Chemotherapeutic Agents Targeting Prostate Cancer Cells.

We report that the pincer nickel complexes display prostate cancer antitumor properties through inhibition of cell proliferation. Notably, they display better antitumor properties than cisplatin. Mechanistic studies reveal that these pincer nickel complexes trigger cell apoptosis, most likely due to cell cycle arrest. Interestingly, these complexes also inhibit androgen receptor (AR) and prostate-specific antigen (PSA) signaling, which are critical for prostate cancer survival and progression. Our study reveals a novel function of pincer nickel complexes as potential therapeutic drugs in prostate cancer.

Potential Biomolecules Capable of Assessing Risk of Osteoporotic Fracture: A Scoping Review.

Osteoporosis as a systemic chronic skeletal disease is characterized by low bone mineral density and increased risk to osteoporotic fractures. Osteoporosis is prevalent in the middle-aged and elderly population, especially in the postmenopausal women. With population aging, osteoporosis has become a world-wide serious public health problem. Early recognition of the high-risk population followed by timely and efficient intervention and/or treatment is important for preventing osteoporotic fractures. In light of the high heritability and complex pathogenesis of osteoporosis, comprehensive consideration of vital biological/biochemical factors is necessary for accurate risk evaluation of fractures. For this purpose, we review recent research progress on molecules which can be applied to assess risk for osteoporotic fractures. Future integrative analyses and systematic evaluation of these molecules may facilitate developing novel methodologies and/or test strategies, i.e., biochips, for early recognition of osteoporosis, hence contributing to preventing osteoporotic fractures.

Modeling and prediction of the transmission dynamics of COVID-19 based on the SINDy-LM method.

The transmission dynamics of COVID-19 is investigated in this study. A SINDy-LM modeling method that can effectively balance model complexity and prediction accuracy is proposed based on data-driven technique. First, the Sparse Identification of Nonlinear Dynamical systems (SINDy) method is used to discover and describe the nonlinear functional relationship between the dynamic terms in the model in accordance with the observation data of the COVID-19 epidemic. Moreover, the Levenberg-Marquardt (LM) algorithm is utilized to optimize the obtained model for improving the accuracy of the SINDy algorithm. Second, the obtained model, which is consistent with the logistic model in mathematical form with small errors and high robustness, is leveraged to review the epidemic situation in China. Otherwise, the evolution of the epidemic in Australia and Egypt is predicted, which demonstrates that this method has universality for constructing the global COVID-19 model. The proposed model is also compared with the extreme learning machine (ELM), which shows that the prediction accuracy of the SINDy-LM method outperforms that of the ELM method and the generated model has higher sparsity.

The effect of light on follicular development in laying hens.

OBJECTIVE: The oxidative stress status and changes of chicken ovary tissue after shading were studied, to determine the mechanism of the effect of shading on follicular development. METHODS: Twenty healthy laying hens (40 weeks old) with uniform body weight and the same laying rate were randomly divided into two groups (the shading group and normal light group). In the shading group, the cage was covered to reduce the light intensity inside the cage to 0 without affecting ventilation or food intake. The normal lighting group received no additional treatment. After 7 days of shading, oxidative stress related indicators and gene expression were detected. RESULTS: Analysis of paraffin and ultrathin sections showed that apoptosis of ovarian granulosa cells (GCs) increased significantly after light shading. Enzyme linked immunosorbent assay results revealed that the levels of total antioxidant capacity, malondialdehyde, superoxide dismutase (SOD), glutathione, catalase (CAT), and other substances in the sera, livers, ovaries, and follicular GCs of laying hens increased significantly after shading for 7 days; and reactive oxygen species (ROS) levels in the livers of laying hens also increased significantly. ROS in the serum, ovarian and GCs also increased. After shading for 7 days, the levels of 8-hydroxy-2 deoxyguanosine in the sera and ovarian tissues of laying hens increased significantly. Cell counting kit-8 detection showed that the proliferation activity of GCs in layer follicles decreased after shading for 7 days; the expression level of the anti-apoptotic gene B-cell lymphoma-2 in ovarian tissue and follicular GCs was significantly reduced, and the expression levels of pro-apoptotic caspase 3 (casp3), and SOD, glutathione peroxidase 2 (GPX2), and CAT were all significantly increased. CONCLUSION: Oxidative stress induced by shading light has a serious inhibitory effect on follicular development during reproduction in laying hens.

An interventional radiology technique to treat pharyngeal or esophageal perforation associated with mediastinal abscess in children.

PURPOSE: Pharyngeal or esophageal perforation with mediastinal abscess is notably dangerous in children and can be very difficult to treat. We aimed to determine the safety and efficacy of the transnasal placement of a mediastinal drainage catheter and a nasojejunal feeding tube, with or without gastric decompression, in the treatment of the above perforations in children. METHODS: We placed transnasal mediastinal drainage catheters and nasojejunal feeding tubes in 14 pediatric patients. Patients with esophageal perforation also underwent the placement of a gastric decompression tube. Four of these patients additionally received chest drainage tubes. RESULTS: The fistula healed after a median of 66 days (range, 5-404 days). Corrosive esophagitis occurred in two patients with pharyngeal perforations. One of these patients underwent surgical treatment 2 months after fistula healing, and the other underwent repeated balloon dilatation procedures for cicatricial restenosis. Four months after the fistula had healed, the patients with esophageal perforations were all free from recurrence. CONCLUSION: The use of interventional radiology to place a transnasal mediastinal drainage catheter, a nasojejunal feeding tube, and a gastric decompression tube is a safe, easy, inexpensive, and efficacious way to treat pharyngeal or esophageal perforation complicated by mediastinal abscess in children. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma.

Long non-coding RNAs (lncRNAs) have been confirmed to be aberrantly expressed and involved in the progression of neuroblastoma. This study aimed to explore the expression profile of lncRNA X-inactive specific transcript (XIST) and its functional involvement in neuroblastoma. In this study, the relative level of XIST in neuroblastoma tissues and cell lines was detected by qPCR, and DKK1 protein expression was determined using western blot. The effect of XIST on cell growth, invasion and migration in vitro and in tumorigenesis of neuroblastoma was assessed. The level of H3K27me3 in DKK1 promoter was analyzed with ChIP-qPCR. Interaction between XIST and EZH2 was verified by RNA immunoprecipitation (RIP) and RNA pull-down assay. XIST was significantly upregulated in neuroblastoma tissues (n = 30) and cells lines, and it was statistically associated with the age and International Neuroblastoma Staging System (INSS) staging in neuroblastoma patients. Downregulation of XIST suppressed the growth, migration and invasion of neuroblastoma cells. EZH2 inhibited DKK1 expression through inducing H3 histone methylation in its promoter. XIST increased the level of H3K27me3 in DKK1 promoter via interacting with EZH2. Downregulation of XIST increased DKK1 expression to suppress neuroblastoma cell growth, invasion, and migration, which markedly restrained the tumor progression. In conclusion, XIST downregulated DKK1 by inducing H3 histone methylation via EZH2, thereby facilitating the growth, migration and invasion of neuroblastoma cells and retarding tumor progression.

Advances in the Surgical Treatment of Neuroblastoma.

OBJECTIVE: This study was to review the efficacy of surgical resections in different clinical situations for a better understanding of the meaning of surgery in the treatment of neuroblastoma (NB). DATA SOURCES: The online database ScienceDirect (201-2018) was utilized. The search was conducted using the keywords "neuroblastoma," "neuroblastoma resection," "neuroblastoma surgery," and "high-risk neuroblastoma." STUDY SELECTION: We retrospectively analyzed of patients who underwent surgical resections in different clinical situations. The article included findings from selected relevant randomized controlled trials, systematic reviews, and meta-analyses or good-quality observational studies. Abstracts only, letters, and editorial notes were excluded. Full-text articles and abstracts were extracted and reviewed to identify key articles discussing surgery management of NB, which were then selected for critical analysis. RESULTS: A total of 7800 English language articles were found containing references to NB (201-2018). The 163 articles were searched which were related to the surgical treatment of NB (201-2018). Through the analysis of these important articles, we found that the treatments of NB at low- and intermediate-risk groups were basically the same. High-risk patients remained controversial. CONCLUSIONS: NB prognosis varies tremendously based on the stage and biologic features of the tumor. After reviewing the relevant literature, patients with low-risk disease are often managed with surgical resection or observation alone with tumors likely to spontaneously regress that are not causing symptoms. Intermediate patients are treated with chemotherapy with the number of cycles depending on their response as well as surgical resection of the primary tumor. High-risk patients remain controversial. Multidisciplinary intensive treatment is essential, especially for patients who received subtotal tumor resection. Minimally invasive surgery for the treatment of NBs without image-defined risk factors in low- to high-risk patients is safe and feasible and does not compromise the treatment outcome. We conclude that ≥90% resection of the primary tumor is both feasible and safe in most patients with high-risk NB. New targeted therapies are crucial to improve survival.

Comparison of Micro-Clamping Stent-Retriever Thrombectomy with Conventional Stent-Retriever Thrombectomy in Intracranial Large Vessel Embolism.

OBJECTIVE: To evaluate the effectiveness of micro-clamping stent-retriever thrombectomy (MSRT) in patients with acute ischemic stroke with intracranial large vessel embolism (ILVE), and compare it with that of conventional stent-retriever thrombectomy (CSRT). METHODS: We retrospectively evaluated 108 patients with ILVA treated by MSRT (n = 52) or CSRT (n = 56) from the 2 participating institutions between January 2016 and November 2017. The rates of successful (Modified Thrombolysis in Cerebral Infarction [mTICI] grade 2b or 3) and complete reperfusion (mTICI grade 3), time from guide catheter placement to reperfusion, rates of first-pass success, and the number of passes for reperfusion were compared between the MSRT and CSRT groups. RESULTS: The complete reperfusion (mTICI 3) rates by MSRT were significantly higher than those achieved with CSRT (78.8% [41/52] vs. 57.1% [32/56], respectively; P = 0.016). Successful reperfusion (mTICI 2b or 3) rates were 92.3% (48/52) in the MSRT group and 83.9% (47/56) in the CSRT groups (P = 0.181). The mean number of passes for reperfusion was significantly lower with MSRT compared with CSRT (1.5 ± 0.2 vs. 2.5 ± 0.5, respectively; P = 0.001). The first-pass success rates were significantly higher in the MSRT group than in the CSRT group (65.4% [34/52] vs. 28.6% [16/56]; P = 0.0001). The mean time from guide catheter placement to reperfusion was significantly shorter in the MSRT group (20.5 ± 6.6 minutes vs. 46.3 ± 7.6 minutes; P = 0.001). CONCLUSIONS: These findings suggest that the complete reperfusion rates and mechanical thrombectomy efficiency in patients with ILVE are better after MSRT compared with CSRT.

DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation.

Inflammation and oxidative stress are significantly involved in the progression of a variety of diseases, including myocardial ischemia/reperfusion (IR). In the present study, we hypothesized a protective role of dual-specificity phosphatase 14 (DUSP14) in myocardial IR, as well as the underlying molecular mechanism. The results indicated that DUSP14 was down-regulated following cardiac IR injury. Subsequently, the wild type (WT) and DUSP14-knockout (KO) mice were included to further reveal the potential role of DUSP14 in cardiac IR injury progression. DUSP14-KO mice exhibited increased infarction area and elevated apoptosis, as evidenced by the increased TUNEL-positive cells in ischemia heart following reperfusion compared to WT mice. Further, DUSP14-KO significantly aggregated cardiac dysfunction of mice after IR injury. Cardiac IR injury to DUSP14-KO mice led to markedly increased expression of pro-inflammatory cytokines and activated nuclear factor-κB (NF-κB) pathway in the heart in comparison to WT mice. Meanwhile, mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK, were significantly activated by DUSO14-KO in mice after IR injury. Compared to WT mice, DUSP14-KO mice showed markedly increased oxidative stress markers in cardiac tissues, including malondialdehyde (MDA), NADPH oxidase-4 (NOX4) and p47, while decreased activities or expressions of anti-oxidants, such as glutathione (GSH), glutathione peroxidase (GPx), glutathion reductases (GR), superoxide dismutase (SOD) and hemeoxygenase-1 (HO-1). DUSP14-knockdown (KD) in primary cardiomyocytes using its specific siRNA sequence elevated hypoxia and reoxygenation (HR)-induced activation of NF-κB and MAPKs signaling pathways, and reactive oxygen species (ROS) generation. Intriguingly, pre-treatment of ROS scavenger, N-acetylcysteine (NAC), markedly abolished DUSP14-KD-augmented NF-κB and MAPKs activation in HR-stimulated primary cardiomyocytes. Together, the results above indicated that DUSP14 might be served as a positive regulator to attenuate cardiac IR injury. Suppressing DUSP14 exacerbated cardiac injury through activating NF-κB and MAPKs signaling pathways regulated by ROS production. Thus, DUSP14 could be a valuable target for developing treatments for myocardial IR injury.

Concomitant modulation of PTEN and Livin in gastric cancer treatment.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Livin are important in the development of gastric cancer (GC). PTEN and Livin are involved in the regulation of tumor cell proliferation, migration and apoptosis. The modulation of PTEN or Livin has been investigated extensively in various cancer models. However, no studies have been performed to evaluate the combined effect of concurrently modulating these two genes on the development of GC. In the present study, the BGC823 human gastric carcinoma cell line was transfected with a dual gene modified vector (pCL-neo-PTEN-siLivin) in parallel with single gene modified vectors (pCL­neo­PTEN or pRNAT­U6.1­siLivin), and an empty control vector. Dual gene modulation (pCL­neo­PTEN­siLivin) had a more marked effect on the inhibition of cell proliferation, induction of apoptosis, and reduction of cell penetration in Matrigel, compared with either single gene alone or empty vector transfection. In a xenograft nude mouse model, the inoculation of pCL­neo­PTEN­siLivin­transfected BGC823 cells led to a markedly reduced tumor burden, compared with that in all other inoculation groups. In conclusion, the overexpression of PTEN concomitant with Livin gene silencing was confirmed as a feasible and effective in vitro and in vivo gene modulation method, which may represent a potential therapeutic strategy for the treatment of GC.

Thrombectomy Using "Clamping Embolus with Semi-Retrieval" Technique in Acute Ischemic Stroke.

BACKGROUND: Embolization of thrombus fragments in new or downstream vascular territories is a potential adverse event in neurothrombectomy, requiring additional repeated thrombectomy attempts. This study aims to describe technical results of the thrombectomy with clamping embolus technique (TCET) method in acute ischemic stroke. This study also aims to evaluate the efficiency of mechanical thrombectomy by TCET, and to compare it with conventional stent retriever thrombectomy (CSRT). MATERIALS AND METHODS: A retrospective analysis was performed in 52 consecutive patients treated between January 2015 and October 2016 for intracranial large vessel occlusion by stent retriever thrombectomy. Recanalization rates, procedure durations, and thrombectomy attempts were compared between the TCET and the CSRT groups. RESULTS: Successful recanalization (thrombolysis in cerebral infarction [TICI] 2b or 3) with TCET was achieved in 91.7% (22 of 24) versus 92.9% (26 of 28) in the CSRT group (P = .921). To preserve the restored patency of severely affected atherosclerotic intracranial vessels, 7 and 8 patients received angioplasty or stenting in the TCET and CSRT groups, respectively. In embolic cases, the number of thrombectomy attempts with TCET was significantly lower than that obtained with CSRT (1.7 ± .2 versus 2.6 ± .5, respectively; P = .001); the one-pass thrombectomy rate was significantly higher in the TCET group than in the CSRT-treated patients (58.8% versus 25.0%, respectively; P = .014). Procedure duration was significantly shorter by TCET than by CSRT (35.8 ± 5.8 minutes versus 55.5 ± 7.2 minutes, respectively; P = .001). CONCLUSIONS: The efficiency of mechanical thrombectomy by TCET in acute ischemic stroke might be improved compared with CSRT.

Distribution and morphology of ghrelin-immunopositive cells in the thymus of the African ostrich / Distribución y morfología de células inmunopositivas de la ghrelina en el timo de la avestruz africana

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has been detected in the thymus of multiple vertebrates. However, little is known about its distribution in the thymus of the African ostrich. In this study, we evaluated the distribution and morphological characteristics of ghrelin-producing cells in the thymus of the African ostrich. Our results revealed that the thymus consists of a capsule and a parenchyma, which comprises the cortex and medulla. Compared to the cortex, the medulla had a fewer number of thymocytes and a greater number of epithelial cells. Additionally, three thymic corpuscles were identified. Ghrelin-immunopositive (ghrelin-ip) cells were detected both in the cortex and medulla of the African ostrich thymus, specifically within epithelial cells and thymic corpuscles. On the other hand, no ghrelin-ip cells were detected within thymocytes. These results clearly demonstrate the presence of ghrelin-ip cells in the thymus of the African ostrich.

La ghrelina, un ligando endógeno para el receptor secretor de la hormona del crecimiento, se ha detectado en el timo de múltiples vertebrados. Sin embargo, poco se sabe sobre su distribución en el timo de la avestruz africana. En este estudio se evaluó la distribución y características morfológicas de las células productoras de ghrelina en el timo de la avestruz africana. Nuestros resultados revelaron que el timo consiste en una cápsula y un parénquima, que comprende la corteza y la médula. En comparación con la corteza, se observó un número menor de timocitos en la médula y un mayor número de células epiteliales. Además, se identificaron tres corpúsculos tímicos. Se detectaron células inmunopositivas a la ghrelina (ghrelin-ip) tanto en la corteza como en la médula del timo de la avestruz africana, específicamente dentro de células epiteliales y corpúsculos tímicos. Por otra parte, no se detectaron células ghrelin-ip dentro de los timocitos. Estos resultados demuestran claramente la presencia de células ghrelin-ip en el timo de la avestruz africana.

Outcomes of Coronary Artery Bypass and Stents for Unprotected Left Main Coronary Stenosis.

BACKGROUND: This study assessed the short-, medium-, and long-term outcomes of coronary artery bypass grafting vs stenting for patients with unprotected left main coronary artery disease through a meta-analysis of randomized controlled trials. METHODS: PubMed, Embase, Scopus, Web of Science, Cochrane Library, and major conference proceedings databases were systematically searched for randomized controlled trials of coronary artery bypass grafting compared with stents in unprotected left main coronary artery disease. End points assessed were all-cause death, myocardial infarction, major adverse cardiac and cerebrovascular events, target vessel revascularization, and cerebral stroke. A meta-analysis was conducted according to predefined clinical end points. RESULTS: All-cause death and stroke were similar between stenting and coronary artery bypass grafting at 1 year and at follow-up beyond 1 year. The incidence of myocardial infarction was similar between stenting and coronary artery bypass grafting at each separate time point. The incidence of repeat revascularization was similar between the two groups at 30 days but was higher for stenting at 1 year and beyond. There was a trend toward fewer major adverse cardiac and cerebrovascular events after stenting compared with coronary artery bypass grafting at 30 days, but this difference was no longer significant at 1 year and reversed at follow-up beyond 1 year. CONCLUSIONS: The early advantages of stenting over coronary artery bypass grafting have been shown to progressively shift to coronary artery bypass grafting over time. Further larger sample randomized controlled trials are warranted to confirm the results.

microRNA-761 induces aggressive phenotypes in triple-negative breast cancer cells by repressing TRIM29 expression.

PURPOSE: Despite advances that have been made in systemic chemotherapy, the prognosis of advanced triple-negative breast cancer (TNBC) patients is still poor. The identification of key factors governing TNBC development is considered imperative for the development of novel effective therapeutic approaches. Previously, it has been reported that microRNA (miR)-761 may act as either a tumor suppressor or as an oncogene in different types of cancer. Here, we aimed at assessing the biological role of this miRNA in TNBC. METHODS: First, we measured the expression of miR-761 in primary breast cancer tissues and breast cancer-derived cell lines using qRT-PCR. Subsequently, over-expression and silencing experiments were performed to determine the role of miR-761 in TNBC cell proliferation, colony formation, migration and invasion in vitro. The in vivo role of miR-761 in TNBC growth and metastasis was determined in mouse models. Bioinformatics analyses, dual-luciferase reporter assays, Western blot analyses and rescue experiments were performed to identify miR-761 target gene(s). RESULTS: We found that miR-761 was up-regulated in primary breast cancer tissues and its derived cell lines and, particularly, in TNBC tissues and cell lines. We also found that exogenous miR-761 over-expression augmented in vitro TNBC cell proliferation, colony formation, migration and invasion, whereas miR-761 down-regulation impaired these features. In vivo, we found that miR-761 over-expression facilitated TNBC growth and lung metastasis. Mechanistically, miR-761 was found to negatively regulate the expression of tripartite motif-containing 29 (TRIM29) in TNBC cells by binding to the 3'-untranslated region of its mRNA. In conformity with these results, a significant negative correlation between miR-761 expression and TRIM29 protein expression was noted in primary TNBC tissues (r = -0.452, p = 0.0126). We also found that exogenous TRIM29 over-expression reversed the proliferative and invasive capacities of TNBC cells. CONCLUSIONS: Our data indicate that miR-761 acts as an oncogene in TNBC. This mode of action can, at least partially, be ascribed to the down-regulation of its target TRIM29. We suggest that miR-761 may serve as a promising therapeutic target for TNBC.

Preliminary investigation of methylation status of microRNA-124a in spinal cords of rat fetuses with congenital spina bifida.

OBJECTIVE: We investigated the expression of microRNA-124a and its methylation status in the spinal cords of rats with congenital spina bifida versus rats with normal fetuses. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction was used to compare the expression of microRNA-124a in the spinal cords of 42 rats with all-trans retinoic acid induced congenital spina bifida and 42 rats with normal fetuses. The DNA methylation status in the promoter region of miRNA-124a was detected using methylation specific-PCR. RESULTS: Compared with rats with normal fetuses, expression of microRNA-124a was significantly decreased in rats with congenital spina bifida fetuses. The percentages of spinal cords with DNA hypermethylation in the microRNA-124a promoter were 81% and 14% in the congenital spina bifida and normal control groups, respectively. The difference was statistically significant. Further apoptosis testing revealed increased apoptosis cell numbers in the congenital spina bifida samples. Meanwhile, the phosphorylated mitogen-activated protein kinase protein expression level dramatically decreased in the congenital spina bifida samples. CONCLUSION: Aberrant DNA methylation was responsible for down-regulation of microRNA-124a by regulating the mitogen-activated protein kinase pathway, suggesting that microRNA-124a is a potential diagnostic biomarker in congenital spina bifida.