Innate immune response restarts adaptive immune response in tumors.

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the anti-tumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy.

Quantitation of macropinocytosis in glioblastoma based on high-content analysis.

BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.

Y-shaped shunt for the treatment of Dandy-Walker malformation combined with giant arachnoid cysts: A case report.

BACKGROUND: Dandy-Walker malformation (DWM) was first reported in 1914. In this case report, a pediatric case was complicated with giant and isolated arachnoid cysts in the right cerebellar hemisphere along with the typical DWM. CASE SUMMARY: The patient was at 20 mo old boy, with the complaint of staggering for more than 2 mo. He was admitted to the hospital due to high intracranial pressure and staggering. At admission, the patient had typical manifestations of high intracranial pressure, including vomiting, poor appetite and feeding difficulty. Physical examination revealed increased head circumference, closed anterior fontanelle, unstable standing, staggering, leaning right while walking and ataxia. After admission, he was diagnosed with DWM accompanied by giant isolated arachnoid cysts in the posterior fossa. He underwent Y-shaped three-way valve repair for treating differential pressure between the supratentorial hydrocephalus and the subtentorial arachnoid cysts at once. The child recovered well after the surgery. CONCLUSION: In this case, supratentorial and subtentorial shunts were placed, which solved the problem of differential pressure between the supratentorial and subtentorial parts simultaneously. This provides useful information regarding treatment exploration in this rare disease.

Myeloperoxidase: a new target for the treatment of stroke?

Myeloperoxidase is an important inflammatory factor in the myeloid system, primarily expressed in neutrophils and microglia. Myeloperoxidase and its active products participate in the occurrence and development of hemorrhagic and ischemic stroke, including damage to the blood-brain barrier and brain. As a specific inflammatory marker, myeloperoxidase can be used in the evaluation of vascular disease occurrence and development in stroke, and a large amount of experimental and clinical data has indicated that the inhibition or lack of myeloperoxidase has positive impacts on stroke prognosis. Many studies have also shown that there is a correlation between the overexpression of myeloperoxidase and the risk of stroke. The occurrence of stroke not only refers to the first occurrence but also includes recurrence. Therefore, myeloperoxidase is significant for the clinical evaluation and prognosis of stroke. This paper reviews the potential role played by myeloperoxidase in the development of vascular injury and secondary brain injury after stroke and explores the effects of inhibiting myeloperoxidase on stroke prognosis. This paper also analyzes the significance of myeloperoxidase etiology in the occurrence and development of stroke and discusses whether myeloperoxidase can be used as a target for the treatment and prediction of stroke.

The mechanism of non-coding RNAs in medulloblastoma.

Medulloblastoma (MB) is one of the most common malignant tumors of the central nervous system in children. Although surgery, radiotherapy and chemotherapy have resulted in considerable progress in the treatment of this disease, the prognosis of patients with MB remains very poor. Therefore, highly specific molecular targeted treatment, which can improve the therapeutic efficacy and reduce the side effects of MB, has become a research hotspot. In recent years, non-coding RNAs (ncRNAs), which were initially considered to be transcriptional noise, have been shown to possess regulatory functions. A series of ncRNAs have been identified, including microRNAs and circular RNAs, which affect the expression of specific genes in a variety of tumors. These genes lead to the formation of a specific complex of proteins or they directly participate in protein synthesis in order to regulate the occurrence and development of tumors. The aim of the present review article was to summarize the recent research studies that have explored the ability of ncRNAs to regulate the occurrence and development of MB.

The Inhibitory Effect of miR-345 on Glioma Progression Is Closely Related to circRNA-hsa_circ_0073237 and HDGF.

Glioma is the most common primary malignant tumor of the central nervous system and has a poor prognosis. Therefore, exploring the key molecular targets is a new opportunity for basic research and clinical treatment of glioma. Previous studies found that circRNA-hsa_circ_0073237 was upregulated in gliomas. Our further analyses of the biological function and molecular mechanism of hsa_circ_0073237 showed that hsa_circ_0073237 was also upregulated in glioma cell lines and could combine with miR-345 to inhibit its expression. miR-345 was downregulated in glioma tissues and cells, and targeted to regulate the expression of hepatoma-derived growth factor (HDGF), while HDGF expression was enhanced in glioma. Hsa_circ_0073237 promoted the expression of HDGF in glioma cells by adsorbing miR-345. Hsa_circ_0073237 siRNA, miR-345, and HDGF siRNA effectively inhibited cell viability and invasion and promoted cell apoptosis. When expression of hsa_circ_0073237 and miR-345 was inhibited simultaneously, cell viability, apoptosis, and invasion did not change significantly; however, after transfection with HDGF overexpression vector, the effects of hsa_circ_0073237 siRNA and miR-345 on glioma cell viability, apoptosis, and invasion were obviously reversed. Further construction of glioma xenograft models in nude mice confirmed that the introduction of miR-345 in vivo effectively inhibited tumor growth, significantly reduced tumor diameter and weight, and obviously decreased the expression of HDGF. Therefore, hsa_circ_0073237 can regulate the biological functions of glioma cells through miR-345/HDGF, thereby affecting the progression of tumors, indicating that the hsa_circ_0073237/miR-345/HDGF pathway may be a key target for the treatment of glioma.

UBE2R2-AS1 Inhibits Xenograft Growth in Nude Mice and Correlates with a Positive Prognosis in Glioma.

Our previous study showed that the lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis through the miR-877-3p/TLR4 pathway. In this study, it was further found that the expression of UBE2R2-AS1 in glioma tissues was decreased significantly, and gradually decreased with increasing clinical stage. Chi-square analysis showed that the expression of UBE2R2-AS1 was significantly correlated with the WHO stage of tumor and epilepsy. Using Kaplan-Meier univariate survival analysis, it was found that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma, while multiple Cox regression analysis showed that the expression of UBE2R2-AS1 correlated positively with the overall survival of patients with glioma as a protective factor for glioma prognosis. The analysis of data from TCGA also showed that patients with high UBE2R2-AS1 levels or low miR-877-3p expression were more likely to have good survival outcomes. Further construction of a glioma xenograft model in nude mice showed that UBE2R2-AS1 overexpression inhibited the growth of tumors, and the inhibition of miR-877-3p expression had a similar effect. Simultaneous UBE2R2-AS1 overexpression and miR-877-3p inhibition further decreased the growth rate of tumors in nude mice. Taken together, the results of our study suggest that UBE2R2-AS1 is an important tumor suppressor gene in glioma, which may be a good marker and treatment target for the clinical detection of glioma.

Inhibition of fruit softening by cold plasma treatments: affecting factors and applications.

Softening is a common phenomenon of texture changes associated with plant cell walls, inducing a decrease in the quality of fruit. Inhibiting the softening is effective to extend the shelf life of fruit. Cold plasma (CP), as a novel nonthermal technology, has been applied to keep the freshness of the fruit. This review centers on applying cold plasma treatments to the inhibition of fruit softening. Different pathways for inhibiting fruit softening by CP treatments, including maintenance of fruit firmness, reduction in the activities of enzymes, inactivation of fungal pathogens and lowering of respiration rates, are discussed. The biochemistry of fruit softening and the fundamental of cold plasma are also presented. In general, among all postharvest technologies, cold plasma is a promising method with many advantages, showing great potential in maintaining the quality and inhibiting the softening of the fruit. Future work should focus on process optimization to achieve better results in maintaining fruit freshness, and commercial applications of cold plasma technology should also be explored.

Emergence of a Complete Heavy-Quark Spin Symmetry Multiplet: Seven Molecular Pentaquarks in Light of the Latest LHCb Analysis.

A recent analysis by the LHCb Collaboration suggests the existence of three narrow pentaquarklike states-the P_{c}(4312), P_{c}(4440), and P_{c}(4457)-instead of just one in the previous analysis [the P_{c}(4450)]. The closeness of the P_{c}(4312) to the D[over ¯]Σ_{c} threshold and the P_{c}(4440) and P_{c}(4457) to the D[over ¯]^{*}Σ_{c} threshold suggests a molecular interpretation of these resonances. We show that these three pentaquarklike resonances can be naturally accommodated in a contact-range effective field theory description that incorporates heavy-quark spin symmetry. This description leads to the prediction of all the seven possible S-wave heavy antimeson-baryon molecules [that is, there should be four additional molecular pentaquarks in addition to the P_{c}(4312), P_{c}(4440), and P_{c}(4457)], providing the first example of a heavy-quark spin symmetry molecular multiplet that is complete. If this is confirmed, it will not only give us an impressive example of the application of heavy-quark symmetries and effective field theories in hadron physics, it will also uncover a clear and powerful ordering principle for the molecular spectrum, reminiscent of the SU(3)-flavor multiplets to which the light hadron spectrum conforms.

Long noncoding RNA UBE2R2-AS1 promotes glioma cell apoptosis via targeting the miR-877-3p/TLR4 axis.

Introduction: Brain glioma is the most common type of primary malignancy in the central nervous system (CNS), with high recurrence and mortality rate, especially glioblastoma (GBM). Recent evidence suggests a role for many long noncoding RNAs (lncRNAs) in the pathogenesis, proliferation, apoptosis, metastasis, and chemotherapeutic resistance of cancer cells. Although the functions of some lncRNAs in the occurrence and development of gliomas have been confirmed, detailed mechanisms of action are lacking. Furthermore, the biological roles of many other lncRNAs in glioma have not been reported at all. Methods: In this study, we identified a novel lncRNA, UBE2R2-AS1, which was dramatically downregulated in glioma compared with normal tissue, by performing microarray detection of six pairs of glioma samples and adjacent normal tissues. In vitro experiments demonstrated that UBE2R2-AS1 regulated glioma cell proliferation, apoptosis, and migration. Results: UBE2R2-AS1 acted as a competing endogenous RNA (ceRNA) to target Toll-like receptor 4 (TLR4) mRNA by binding to miR-877-3p. Furthermore, lncRNA UBE2R2-AS1 suppressed glioblastoma cell growth, migration, and invasion, as well as promoting cell apoptosis by targeting miR-877-3p/TLR4 directly. Conclusion: This information regarding UBE2R2-AS1 and its glioma-related molecular mechanisms will aid the future identification of new lncRNA-directed diagnostics and drug-targeting therapies.

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Understanding the effects of land use patterns on soil water and gas transport in the water-wind erosion crisscross region can provide guidance for high-efficiency use of limited soil and water resource in the ecological rehabilitation process on the Loess Plateau. To investigate the cha-racteristics of soil water and gas transport under different land use patterns and to study the relationships between soil saturated hydraulic conductivity (Ks), air permeability (Ka) and relative gas diffusivity (DP/D0), we collected soil samples (0-5 cm depth) from Caragana korshinskii land, abandoned land, alfalfa land, cropland, and bare land. Ks was measured by constant-head method. DP/D0 was measured by gas chamber method. Ka under field capacity (FC) was measured using the soil gas permeability meter. Results showed that soil bulk density (ρb) ranked as alfalfa land>bare land>abandoned land>C. korshinskii land >cropland, with that of abandoned land, bare land and alfalfa land being significantly different from that of cropland. Total soil porosity (Φ) ranked as cropland>C. korshinskii land>abandoned land>bare land>alfalfa land. Compared with cropland, Φ of alfalfa land, bare land and abandoned land was lower by 7.5%, 4.7% and 3.1%, respectively. Air filled porosity (ε100) ranked as cropland>abandoned land>C. korshinskii land>bare land>alfalfa land. ε100 of alfalfa land, bare land, C. korshinskii land and abandoned land was lower by 38.3%, 33.6%, 12.8% and 10.1%, respectively, as compared with cropland. Soil Ks ranked as abandoned land>C. korshinskii land>alfalfa land>bare land>cropland, with that of the abandoned land being significantly higher than the other four land use patterns. Soil Ka ranked as abandoned land>alfalfa land>C. korshinskii land>bare land>cropland, with that of abandoned land being significantly diffe-rent with cropland. Soil DP/D0 ranked as abandoned land> C. korshinskii land> alfalfa land>cropland>bare land, in which DP/D0 of C. korshinskii land and abandoned land was significantly higher than cropland by 36.8% and 61.6%, respectively. There were significant correlations between Ks and Ka, DP/D0 under FC conditions. Land use patterns significantly changed soil permeability. Farmland, abandonment, C. korshinskii, and alfalfa plantation improved hydraulic and gas transport parameters of the surface soil. In contrast, farmland and bare land had poor capability of soil water and gas transport.

HDAC4 gene silencing alleviates epilepsy by inhibition of GABA in a rat model.

OBJECTIVES: Despite the availability of effective antiepileptic drugs, epileptic patients still suffer from intractable seizures and adverse events. Better control of both seizures and fewer side effects is needed in order to enhance the patient's quality of life. We performed the present study with an attempt to explore the effect that HDAC4 gene silencing would have on epilepsy simulated by model rats. Furthermore, the study made additional analysis on the relativity of the HDAC4 gene in regard to its relationship with the gamma-aminobutyric acid (GABA) signaling pathway. MATERIALS AND METHODS: Tremor rats were prepared in order to establish the epilepsy model. The rats would go on to be treated with si-HDAC4 in order to identify roles of the HDAC4 in levels of GABAARα1, GABAARα4, GAD65, GAT-1, and GAT-3. Finally, both electroencephalogram behavior and cognitive function of the rats following the treatment of si-HDAC4 were observed. RESULTS: Levels of the GABAARα1 and GABAARα4 showed an evident increase, while GAD65, GAT-1, and GAT-3 displayed a decline in the epilepsy rats treated with the aforementioned si-HDAC4 when compared with the epilepsy rats. After injection of si-HDAC4, the epilepsy rats presented with a reduction in seizure degree, latency and duration of seizure, amount of scattered epileptic waves, and occurrence of epilepsy, with an improvement in their cognitive function. CONCLUSION: The study highlighted the role that HDAC4 gene silencing played in easing the cases of epilepsy found in the model rats. This was shown to have occurred through the upregulation of both GABAARα1 and GABAARα4 levels, as well as in the downregulation of GAD65, GAT-1, and GAT-3 levels. The evidence provided shows that the HDAC4 gene is likely to present as a new objective in further experimentation in the treatment of epilepsy.

Endoscopic decompression of the optic canal for traumatic optic neuropathy.

PURPOSE: Traumatic optic neuropathy (TON) is a serious complication of head trauma with the incidence rate of 0.5%-5%. The aim of this study was to investigate the therapeutic efficacy of endoscopic decompression of the optic canal for optic nerve injuries. METHODS: In this study, 11 patients treated in our hospital from January 2009 to January 2015 with the visual loss resulting from TON were retrospectively reviewed for preoperative vision, visual evoked potential (VEP) scan, surgical approach, postoperative visual acuity, complications, and follow-up results. RESULTS: All these patients received endoscopic decompression of the optic canal. At the 3-month follow- up, the visual acuity improvement rate of the 11 patients was 45.5%. The vision acuity of 2 cases improved from hand movement to 0.08 and 0.3 after operation. Another patient's vision acuity returned to 0.05 compared to light sensation preoperatively. Two cases had finger counting before surgery but they had a vision acuity of 0.4 and light sensation respectively after surgery. However, the other 6 cases' vision did not improve after surgery. CONCLUSION: Endoscopic decompression of the optic canal is an effective way to cure TON. VEP could be used as an important reference for preoperative and prognosis evaluation. Operative time after trauma is only a relative condition that may affect the therapeutic effect of optic canal decompression. Poor results of this procedure may be related to the severity of the optic nerve injury.

MiR-22 is frequently downregulated in medulloblastomas and inhibits cell proliferation via the novel target PAPST1.

Medulloblastoma is the most frequent malignant central nervous system tumor in children. MicroRNAs (miRs) are small, non-coding RNAs that target protein-coding and non-coding RNAs, and play roles in a variety of cellular processes through regulation of multiple targets. In the present study, we analyzed miR-22 expression and its effect in cell proliferation and apoptosis in medulloblastomas. Quantitative reverse transcription PCR (RT-PCR) revealed significantly lower expression of miR-22 in 19 out of 27 (70%) medulloblastomas, D341, DAOY, ONS-76 medulloblastoma cell lines, compared with normal cerebellum. Forced expression of miR-22 by lentiviral vector transfection reduced cell proliferation and induced apoptosis, while knockdown of miR-22 increased proliferative activity in DAOY and ONS-76 cells. DAOY cells with miR-22 overexpression in nude mice yielded tumors smaller than those originated from control DAOY cells. Microarray analysis in DAOY cells with forced miR-22 expression showed significant changes in expression profiles, PAPST1 being the most significantly (10 folds) downregulated gene. Quantitative RT-PCR revealed PAPST1 mRNA upregulation in 18 out of 27 (67%) medulloblastomas. In addition, a luciferase reporter assay in ONS-76 and DAOY cells suggested that miR-22 directly targets the PAPST1 gene, and lentivirus-mediated knockdown of PAPST1 suppressed proliferation of DAOY and ONS-76 medulloblastoma cells. These results suggest that frequently downregulated miR-22 expression is associated with cell proliferation in medulloblastomas, and this may be at least in part via PAPST1, which is a novel target of miR-22.