Role of HIF-1α in hypercoagulable state of COPD in rats.

OBJECTIVE: To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS: 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS: Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION: HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.

Acupuncture combined with mifepristone improves sex hormones and inflammatory factors in patients with uterine fibroids.

OBJECTIVE: To analyze the therapeutic effect of acupuncture combined with mifepristone on uterine fibroids and its influence on sex hormones and inflammatory factors. METHODS: Data of 102 patients with uterine fibroids admitted to Shanxi Provincial Hospital of Chinese Medicine from January 2019 to January 2022 were retrospectively analyzed. Among them, there were 50 patients treated with mifepristone alone (control group) and 52 patients undergoing combined treatment of acupuncture and mifepristone (observation group). After 2 months of continuous treatment, the therapeutic efficacy, volume of uterine fibroids and uterus, levels of inflammatory factors (C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α)), as well as levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), along with hemodynamic levels and incidence of adverse reactions were recorded and compared between the two groups. Logistic analysis was employed to identify the independent risk factors for the recurrence of uterine fibroids in patients. RESULTS: Compared with the control group, the observation group was identified with significantly higher overall response rate (P < 0.05). The uterine fibroid volume and uterine volume significantly improved in both groups after treatment, and the improvements were more prominent in the observation group than in the control group (P < 0.05). After treatment, the serum CRP and TNF-α were both evidently decreased in the two groups, while levels of E2, FSH, LH and peak blood flow velocity were significantly ameliorated, and the improvements in the observation group were more significant than those in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Alcohol intake and treatment regime were independent risk factors for the recurrence of uterine fibroids in patients. CONCLUSION: Combining acupuncture with mifepristone can significantly improve uterine fibroids, estrogen and progesterone levels, as well as reduce inflammation, with a high level of safety, making it a promising treatment for clinical use.

Calcification circumference, area, and location are associated with carotid stent expansion rate: high-resolution magnetic resonance vessel wall imaging study.

Background: The plaque imaging findings associated with the stent expansion rate (SER) of the carotid artery are not well known. The purpose of this study was to investigate the imaging findings associated with SER. Methods: It was a retrospective investigation. Based on the kind of carotid stents used, retrospective data from 89 patients who had carotid artery stenting (CAS) for atherosclerotic carotid stenosis were gathered and divided into two groups: open-cell stents and closed-cell stents. Patients underwent preoperative carotid high-resolution magnetic resonance vessel wall imaging (HR-VWI). Use HR-VWI to quantitatively evaluate carotid wall thickness and plaque components. Calculate SER using digital subtraction angiography (DSA). All patients' baseline and HR-VWI imaging features were retrospectively analyzed. Simple and multivariable linear regression analysis was used to determine the imaging findings associated with SER of open-cell and closed-cell stents. Results: A total of 89 patients (mean age, 70±8 years; 69 men) were included in the final analysis. Among 89 patients, 35 patients were treated with open-cell stents. Fifty-four patients were treated with closed-cell stents. In the open-cell stents group, the Maximum single-slice calcification circumference score, maximum wall thickness (WTmax), and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that only the Maximum single-slice calcification circumference score (ß=-9.35; 95% CI: -18.15 to -0.56; P=0.03) was associated with SER of open-cell stents. In the closed-cell stents group, the Maximum single-slice calcification circumference score, WTmax, maximum area percentage of calcification, calcification volume, and total calcification location score with P<0.10 in the simple linear regression analysis were included in the multivariable linear regression analysis. The results of the multivariable linear regression revealed that the Maximum area percentage of calcification (ß=-0.67; 95% CI: -1.29 to -0.05; P=0.03), Maximum single-slice calcification circumference score (ß=-8.43; 95% CI: -13.36 to -3.49; P=0.001) and total calcification location score (ß=-0.37; 95% CI: -1.08 to 0.09; P=0.02) were associated with SER of closed-cell stents. Conclusions: Calcified plaques are associated with SER of the carotid artery. Calcification circumference correlates with SER of open-cell stents. Calcification circumference, calcification area, and calcification location are related to SER of closed-cell stents, which may provide a new consideration for clinicians when choosing carotid artery stents.

Network pharmacology of Huatan Tongluo decoction and clinical effects of its combination with acupuncture in the treatment of stroke.

OBJECTIVE: This study was carried out to probe the clinical effect and mechanism of Huatan Tongluo decoction combined with acupuncture in the treatment of patients with ischemic stroke. METHODS: The clinical data of 100 patients with ischemic stroke were retrospectively collected. On the basis of treatment method, they were split into two groups, each with 50 cases: the conventional treatment group (acupuncture) and the combined treatment group (Huatan Tongluo decoction + acupuncture). After treatment, the neurological function and clinical therapeutic effects of the two groups were evaluated. The treatment of ischemic stroke with Huatan Tongluo decoction was studied by the method of traditional Chinese medicine (TCM) network pharmacology. Resources from databases such as GeneCards, TCMSP, PubChem, Swiss Target Prediction, String, and WebGestalt were integrated, in order to screen for targets of stroke treatment, the active compound composition of Huatan Tongluo decoction, and the targets of compound composition by the use of Cytoscape and R language software. Finally, from the perspective of a protein-protein interaction (PPI) co-expression network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significance of Huatan Tongluo decoction in the treatment of ischemic stroke was discussed. RESULTS: The total effectiveness rate in the combined treatment group was superior to the conventional treatment group. The combined group had higher scores of neurological function, limb movement function, and ability to perform daily living tasks than the conventional treatment group (all P < 0.05). 368 pharmacological targets for Huatan Tongluo decoction and a total of 5690 ischemic stroke targets were retrieved from the database, and 215 intersection targets were found. The results of the PPI network indicated that 43 targets, including EGFR (epidermal growth factor receptor), SRC (proto-oncogene, non-receptor tyrosine kinase), PTPN11 (protein tyrosine phosphatase non-receptor type 11), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (serine/threonine kinase 1), VEGFA (vascular endothelial growth factor A), STAT3 (signal transducer and activator of transcription 3), and FYN (FYN proto-oncogene, Src family tyrosine kinase), had the strongest interactions, so they could be used as targets for subsequent basic research verification. The results suggested that pathways such as vascular endothelial growth factor (VEGF) signaling pathway and other pathways were enriched. CONCLUSION: The combination of Huatan Tongluo decoction and acupuncture can help patients with sequelae of stroke promote the regaining of neurological function, thus improving their movement and enhancing their abilities to perform daily living. Huatan Tongluo decoction can mediate the VEGF signaling pathway and other pathways to treat ischemic stroke.

Structural characterization and functional analysis of juvenile hormone acid methyltransferase JHAMT3 from the silkworm, Bombyx mori.

Juvenile hormone acid methyltransferase (JHAMT) is a rate-limiting enzyme of juvenile hormone (JH) biosynthesis in insects. It transfers the methyl group of S-adenosyl methionine to either the carboxyl group of JH acids or farnesoic acid to produce JH. Six JHAMT paralogues have been identified in the silkworm (Bombyx mori); among them, JHAMT1 and JHAMT2 display a methyltransferase activity. Here, the three-dimensional crystal structure of inactive JHAMT3 and the binary complex of JHAMT3 with its cofactor S-adenosyl-l-homocysteine were determined through X-ray crystallization. Comparative structural analysis revealed that JHAMT3 adopted a similar structural pattern to that of functional JHAMT2, which comprised one core Rossmann fold domain and one substrate-binding domain. Similar to JHAMT2, JHAMT3 underwent a conformational change at the Rossmann fold domain because of cofactor binding, which promoted ligand accommodation. However, it exhibited a relatively rigid substrate-binding pocket compared with that of JHAMT2. JHAMT3 was also highly expressed in the silk gland of fourth- and fifth-instar B. mori larvae. The results of expression profiling combined with activity analysis suggested that JHAMT3 might function as a binding protein of JH acids for the regulation of JH acid titers. These findings provide a structural basis for enhancing the understanding of the physiological function of JHAMT3 and a rational framework for the development of potent and specific inhibitors of JHAMT family members.

Epidemiology, Characteristic, and Prognostic Factors of Primary Sporadic Intradural Malignant Peripheral Nerve Sheath Tumor in the Spinal Canal: A Systematic Literature Review.

Purpose: Primary sporadic intradural malignant peripheral nerve sheath tumor (MPNST) in the spinal canal is a type of rare neoplasm with challenging diagnosis and therapy. The overall prognosis of this tumor is markedly different from that of the usual spinal intradural tumors. The purpose of this systematic review is to reduce the misdiagnosis and enhance the prognosis of the disease by reviewing the literature. Methods: PubMed, Medline, and Embase databases were searched for articles in English language published from 1980 to May 2021, yielding 500 potentially relevant articles. The keywords were as follows: "spinal", "malignant peripheral nerve sheath tumor", "neurosarcoma", "malignant schwannoma", and "malignant neurofibroma". Thirteen papers met the eligibility criteria, including 55 cases with spinal intradural primary sporadic MPNSTs, which were confirmed by post-operation pathology. We further analyzed the clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis. Results: Fifty-five spinal intradural primary sporadic MPNSTs from 30 (54.5%) male and 25 (45.5%) female patients with an average age at diagnosis of 40 years (range, 3-70 years) were included in the study. The most common clinical manifestations were local or radicular pain and motor disturbance. All tumors had significant enhancement and heterogeneous enhancement was more common. Out of 18 lesions, 14 were diagnosed as high grade and the remaining 4 were diagnosed as low grade. The ki-67 labeling index ranged from 5% to 60%. The median recurrence and survival time were 36 and 72 months, respectively. The log-rank tests indicated that significant predictors of OS were patient age (≤30 vs. >30 years) at the time of diagnosis and the presence of metastatic disease, and similar analyses for RFS demonstrated that the presence of metastatic disease was the only significant predictor (60 vs. 10 months). The multivariate Cox proportional hazards regression analysis revealed that absence of metastasis was an independent factor for predicting a favorable prognosis. Conclusions: Spinal intradural primary sporadic MPNSTs are challenging malignant tumors without a systematic treatment plan. The factors affecting its prognosis are not clear. Even after surgical treatment and adjuvant treatment, the recurrence rate and mortality rate are still high. Clinicians should be alert to the possibility of this disease and achieve early detection and treatment.

Transcutaneous electrical acupoint stimulation affects older adults' cognition after general anesthesia: A meta-analysis.

Perioperative neurocognitive dysfunction comprises pre-existing neurocognitive dysfunction, postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). This meta-analysis aims to study the effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive function after general anesthesia in older adults. Eight databases were searched, from the establishment of the databases to January 2022. Eighteen randomized controlled trials were included. TEAS reduced POCD incidence on the 1st and 3rd but not on the 5th and 7th postoperative days (p<0.00001; p<0.00001; p = 0.20; p = 0.30). Owing to the limited number of original studies, POD incidence could not be analyzed. TEAS improved the MMSE scores on the 1st and 3rd but not on the 5th and 7th postoperative days. TEAS reduced the values of S100ß at the end of the surgery and 1 day after surgery and IL-6 on the 1st postoperative day. TEAS can prevent early postoperative cognitive decline after general anesthesia in older adults.

The Role of Graphene Oxide Nanocarriers in Treating Gliomas.

Gliomas are the most common primary malignant tumors of the central nervous system, and their conventional treatment involves maximal safe surgical resection combined with radiotherapy and temozolomide chemotherapy; however, this treatment does not meet the requirements of patients in terms of survival and quality of life. Graphene oxide (GO) has excellent physical and chemical properties and plays an important role in the treatment of gliomas mainly through four applications, viz. direct killing, drug delivery, immunotherapy, and phototherapy. This article reviews research on GO nanocarriers in the treatment of gliomas in recent years and also highlights new ideas for the treatment of these tumors.

Raman spectroscopy: A prospective intraoperative visualization technique for gliomas.

The infiltrative growth and malignant biological behavior of glioma make it one of the most challenging malignant tumors in the brain, and how to maximize the extent of resection (EOR) while minimizing the impact on normal brain tissue is the pursuit of neurosurgeons. The current intraoperative visualization assistance techniques applied in clinical practice suffer from low specificity, slow detection speed and low accuracy, while Raman spectroscopy (RS) is a novel spectroscopy technique gradually developed and applied to clinical practice in recent years, which has the advantages of being non-destructive, rapid and accurate at the same time, allowing excellent intraoperative identification of gliomas. In the present work, the latest research on Raman spectroscopy in glioma is summarized to explore the prospect of Raman spectroscopy in glioma surgery.

Epidemiology and survival of patients with central nervous system solitary fibrous tumors: A population-based analysis.

Background: The objective of this study was to determine population-based estimates of the epidemiology and prognosis of central nervous system solitary fibrous tumors (cSFTs). Methods: We extracted the data of patients diagnosed with cSFTs between 2004 and 2018 from the Surveillance, Epidemiology, and End Results database. We analyzed the distribution of patients according to their demographic and clinical characteristics. Binary logistic regression analysis was performed to predict which patients would be diagnosed with malignant cSFT. Possible prognostic indicators were analyzed by multivariable Cox proportional hazards models. Results: A total of 650 cases were included. The majority of patients were diagnosed at 50-59 years old, and the median age at diagnosis was 55 years. A total of 13.4% of the tumors were located in the spinal canal, and 24% of the tumors were benign. Most of the tumors were larger than 3 cm, but distant metastasis was rare. Tumor resection was the first choice of treatment for these patients, and total resection was achieved in 51.1%. Radiation therapy after surgery was also administered to 42.3% of the patients. The median survival was 57 months. Intracranial tumors and tumors with distant metastasis tended to be malignant. The results of the log-rank test showed that the patients who underwent total resection had better overall survival (OS), but the effect of radiation therapy after surgery was not significant. Conclusion: cSFT is a rare and aggressive type of tumor. Tumor resection is the first choice for treatment, and radiation therapy after surgery does not improve OS. Patients older than 60 years of age who are diagnosed with intracranial tumors, malignant tumors and distant metastasis have worse OS outcomes than their counterparts.

Construction, characterization, and bioavailability evaluation of honokiol-loaded porous starch by melting method without any solvent.

In the present study, the porous starch (PS) was used as an efficient carrier of honokiol (HK), and the HK-loaded PS (HPS) delivery system was prepared by melting method without using organic solvents. Its physical-chemical properties, solubility and oral bioavailability were also investigated. The obtained results proved that the HK in the HPS was mostly amorphous when it was loaded into the PSs with 87.54 ± 1.52% of encapsulation efficiency (EE) and 12.51 ± 0.22% of drug loading (DL) capacity. The water-solubility of the HPS was increased to 115.27 ± 2.92 µg/mL (pH = 1.2, artificial gastric juice (AGJ)), 161.58 ± 3.42 (pH = 6.8, artificial intestinal juice (AIJ)) and 148.5 ± 1.89 µg/mL (pH = 5.5, simulated tumor microenvironment), being 6.07, 4.38 and 4.87-folds higher than free HK. In vitro dissolution tests showed the HK was significantly higher from HPS than from free HK. Furthermore, compared with free HK, the release rate and the bioavailability was also substantially improved for HK from the HPS. Meanwhile, the HPS generated a higher inhibition to HepG2 cells than free HK.

Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1-3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.

Pyrvinium pamoate regulates MGMT expression through suppressing the Wnt/ß-catenin signaling pathway to enhance the glioblastoma sensitivity to temozolomide.

Temozolomide (TMZ) is the mainstream chemotherapeutic drug for treating glioblastoma multiforme (GBM), but the intrinsic or acquired chemoresistance to TMZ has become the leading clinical concern, which is related to the repair of DNA alkylation sites by O6-methylguanine-DNA methyltransferase (MGMT). Pyrvinium pamoate (PP), the FDA-approved anthelminthic drug, has been reported to inhibit the Wnt/ß-catenin pathway within numerous cancer types, and Wnt/ß-catenin signaling pathway can modulate the expression of MGMT gene. However, whether PP affects the expression of MGMT and enhances TMZ sensitivity in GBM cells remains unclear. In the present study, we found that PP and TMZ had synergistic effect on inhibiting the viability of GBM cells, and PP induced inhibition of MGMT and enhanced the TMZ chemosensitivity of GBM cells through down-regulating Wnt/ß-catenin pathway. Moreover, the overexpression of MGMT or ß-catenin weakened the synergy between PP and TMZ. The mechanism of PP in inhibiting the Wnt pathway was indicated that PP resulted in the degradation of ß-catenin via the AKT/GSK3ß/ß-catenin signaling axis. Moreover, Ser552 phosphorylation in ß-catenin, which promotes its nuclear accumulation and transcriptional activity, is blocked by PP that also inhibits the Wnt pathway to some extent. The intracranial GBM mouse model also demonstrated that the synergy between PP and TMZ could be achieved through down-regulating ß-catenin and MGMT, which prolonged the survival time of tumor-bearing mice. Taken together, our data suggest that PP may serve as the prospect medicine to improve the chemotherapeutic effect on GBM, especially for chemoresistant to TMZ induced by MGMT overexpression.

Structural basis for juvenile hormone biosynthesis by the juvenile hormone acid methyltransferase.

Juvenile hormone (JH) acid methyltransferase (JHAMT) is a rate-limiting enzyme that converts JH acids or inactive precursors of JHs to active JHs at the final step of JH biosynthesis in insects and thus presents an excellent target for the development of insect growth regulators or insecticides. However, the three-dimensional properties and catalytic mechanism of this enzyme are not known. Herein, we report the crystal structure of the JHAMT apoenzyme, the three-dimensional holoprotein in binary complex with its cofactor S-adenosyl-l-homocysteine, and the ternary complex with S-adenosyl-l-homocysteine and its substrate methyl farnesoate. These structures reveal the ultrafine definition of the binding patterns for JHAMT with its substrate/cofactor. Comparative structural analyses led to novel findings concerning the structural specificity of the progressive conformational changes required for binding interactions that are induced in the presence of cofactor and substrate. Importantly, structural and biochemical analyses enabled identification of one strictly conserved catalytic Gln/His pair within JHAMTs required for catalysis and further provide a molecular basis for substrate recognition and the catalytic mechanism of JHAMTs. These findings lay the foundation for the mechanistic understanding of JH biosynthesis by JHAMTs and provide a rational framework for the discovery and development of specific JHAMT inhibitors as insect growth regulators or insecticides.

Circular RNA circCCDC66 promotes glioma proliferation by acting as a ceRNA for miR-320a to regulate FOXM1 expression.

BACKGROUND: In this study, we determine the potential roles and uncover the regulatory mechanisms of circCCDC66 in regulating cell growth and cell metastasis of glioma. METHODS: qRT-PCR was used to detect the expressions of circCCDC66 in gliomas and tissues. The biological function of circCCDC66 in glioma cell lines was elucidated by functional experiments. Cell counting kit-8 and transwell were used to detect the effect of circCCDC66 on the proliferation, migration and invasion of glioma cells. Bioinformatics analysis was applied to reveal the targets of circCCDC66. RESULTS: The results showed circCCDC66 was overexpressed in glioma and acted as an oncogene. CircCCDC66 knockdown suppressed the proliferation, migration, and invasion of glioma cells. We constructed a circCCDC66 regulating miRNA network and revealed miR-320a was a potential target of circCCDC66, which was down-regulated in high-grade gliomas compared to low-grade gliomas. Bioinformatics analysis showed circCCDC66-miR-320a/b axis was involved in regulating multiple cancer-related pathways. Furthermore, we identified FOXM1 as a key target of circCCDC66, which was involved in regulating DNA damage response pathways. In mechanism study, circCCDC66 could sponge miR-320a, thereby increasing the expression of FOXM1. CONCLUSIONS: CircCCDC66 could facilitate glioma cells proliferation, invasion and migration by down-regulating miR-320a and up-regulating FOXM1.

Arming wood carbon with carbon-coated mesoporous nickel-silica nanolayer as monolithic composite catalyst for steam reforming of toluene.

Steam reforming is an effective measure for biomass tar elimination as well as H2-rich syngas (H2 + CO) production. However, the granular or powdery Ni-based catalysts are prone to deactivation, which is caused by inappropriate mass transfer and clogging of catalyst bed. Herein, monolithic wood carbon (WC) with low-tortuosity microchannels is armed with a carbon-coated mesoporous nickel-silica nanocomposite (Ni-SiO2@C) layer via an evaporation-induced self-assembly and calcination procedure for toluene (tar model compound) steam reforming. The quality of the Ni-SiO2@C layer growing on the surface of WC microchannel is affected by the molar ratios of Si/Ni feed. A uniform thin-layer coverage is obtained on the Ni-15SiO2@C/WC (Si/Ni = 15) catalyst, where highly dispersed Ni nanoparticles (average size of 6.6 nm) with appropriate metal-support interaction and remarkable mechanical strength are achieved. The mass transfer, coke resistance, and hydrothermal stability of the Ni-15SiO2@C/WC catalyst were significantly improved by the multilevel structure assembled from the WC microchannels and the secondary ordered SiO2 mesopores. A stable toluene conversion over 97% with an H2 yield of 135 µmol/min was obtained at 600 °C on the Ni-15SiO2@C/WC catalyst. This work opens a new window for facilely constructing high-performance wood carbon-based monolithic tar reforming catalyst.

Circular RNA circitga7 accelerates glioma progression via miR-34a-5p/VEGFA axis.

Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.

The Role of the Transcription Factor EGR1 in Cancer.

Early growth response factor 1 (EGR1) is a transcription factor that is mainly involved in the processes of tissue injury, immune responses, and fibrosis. Recent studies have shown that EGR1 is closely related to the initiation and progression of cancer and may participate in tumor cell proliferation, invasion, and metastasis and in tumor angiogenesis. Nonetheless, the specific mechanism whereby EGR1 modulates these processes remains to be elucidated. This review article summarizes possible mechanisms of action of EGR1 in tumorigenesis and tumor progression and may serve as a reference for clinical efficacy predictions and for the discovery of new therapeutic targets.

Lapatinib alleviates TOCP-induced axonal damage in the spinal cord of mouse.

Neuregulin-1 (NRG1), a family of EGF-like factors that activates ErbB receptors, can regulate the proliferation, migration, and myelinating of Schwann cells. We previously reported that NRG1/ErbB signal is responsible for organophosphate (OP)-induced delayed neuropathy (OPIDN) in hens, a susceptive animal model to neuropathic organophosphorous compounds. Our previous study discovered that a neuropathic OP, tri-o-cresyl phosphate (TOCP) activated NRG1/ErbB signaling pathway in both spinal cord and sciatic nerves of hens during the formation of OPIDN and lapatinib, a non-selective antagonist of ErbB1 and ErbB2 receptors, alleviated the toxicity. In this study, we intended to further look into the potential role of NRG1 in the pathogenesis of TOCP-induced axon damage in spinal cord and sciatic nerves and whether lapatinib could also rescue this damage in mice, an OPIDN-resistant animal model. The results revealed that no obvious toxic signs were observed after single TOCP exposure. However, slight histopathological wreck in lumbar spinal cord and sciatic nerves was found following TOCP intoxication, and the damage in sciatic nerves was characterized by axon degeneration of myelin sheath but not the loss of neural skeleton. Only histopathological damage induced by TOCP in spinal cord could be prevented by lapatinib. The translational expression of NRG1/ErbB signaling molecules was analyzed by both in vivo and in vitro studies. In general, NRG1/ErbB pathway was activated by TOCP while combined treatment with lapatinib attenuated TOCP-induced NRG1/ErbB signaling cascade. The results implied that NRG1/ErbB system may predominately play functional role in spinal cord (central nervous system) but not in sciatic nerves (peripheral nervous system) of mouse subjected to neurotoxic OP, which was confirmed by the study in vitro that lapatinib was not able to attenuate TOCP-induced neurotoxicity in rodent Schwann cell line RSC 96 cells.

Effects of end-tidal carbon dioxide levels in patients undergoing direct revascularization for Moyamoya disease and risk factors associated with postoperative complications.

ABSTRACT: A history of transient ischemic attack, severity of disease, urinary output, hematocrit, hypocapnia, and hypotension during direct revascularization (superficial temporal artery to middle cerebral artery [STA-MCA]) in patients with Moyamoya disease (MMD) may lead to a poor prognosis, however, to our knowledge evidence for end-tidal carbon dioxide (ETCO2) targets is lacking. Within the ranges of standardized treatment, the article was primarily designed to study the risk factors associated with the neurologic outcomes during STA-MCA for MMD especially including ETCO2 ranges and the duration in different groups. The primary goals of this study were to investigate the risk factors for neurologic deterioration and explore the association between ETCO2 ranges and neurologic outcome during general anesthesia for STA-MCA.This retrospective observational study included 56 consecutively adult Moyamoya patients who underwent STA-MCA under general anesthesia between January 2015 and August 2019. ETCO2 was summarized per patient every 5 minutes. Clinical outcome was assessed with clinical presentation, computed tomography findings, magnetic resonance imaging findings, cerebral angiography, and the modified Rankin Scale scores at discharge as main outcome measure. The outcomes were also compared for the duration of surgery, anesthesia, and the length of stay.A total of 56 patients were studied, all patients had comprehensive ETCO2 measurements. The incidence of postoperative complications was 44.6% (25/56). There was no association between age, sex, hypertension, diabetes, smoking history, drinking history, sevoflurane use, invasive arterial blood pressure monitoring, combined encephalomyosynangiosis and postoperative complications. Duration of surgery (P = .04), anesthesia (P = .036), hospital stay (P = .023) were significant correlates of postoperative complications. In the multiple logistic regression model, they were not the significant predictors. The ETCO2 ranges and the length of time in different groups within the current clinical setting was not associated with postoperative complications (P > .05).Within a standardized intraoperative treatment strategy, we found that postoperative complications had no significant correlation with sex, age, hypertension, diabetes, smoking history, drinking history, invasive arterial blood pressure monitoring, combined encephalomyosynangiosis, or sevoflurane use. Further, hypocapnia and hypercapnia during STA-MCA were not found to be associated with postoperative complications in patients with MMD.