Aqueous extract of Aconitum carmichaelii Debeaux attenuates sepsis-induced acute lung injury via regulation of TLR4/NF-ΚB pathway

Purpose: To investigate the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced acute lung injury (ALI), as well as explore the underlying mechanism of action. Methods: C57BL/6 mice were treated with AEACD by gavage (4.0 g/kg/day) for 5 days before cecal ligation and puncture (CLP) challenge. After 24 h, the pathological morphology of lung tissue and the biochemical parameters in bronchoalveolar lavage fluid (BALF) were determined by H&E staining and enzyme-linked immunosorbent assay (ELISA). Furthermore, the total protein content and lactate dehydrogenase (LDH) level of BALF, as well as the oxidative biomarkers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)) were evaluated in the lung homogenates by ELISA assay. The levels of pro-inflammatory cytokines, TNFα, IL-1β, and IL-6, in lung tissue were measured by qRT-PCR or ELISA. Finally, key proteins in Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in lung tissue were evaluated by western blot. Results: CLP challenge induced abnormal changes in the histological structures of lung tissue, lung wet-to-dry weight (W/D) ratio, protein content and LDH levels of BALF, which were remarkably reversed by AEACD. In addition, AEACD decreased MDA levels, and increased GSH levels and SOD activity in the lung tissue of CLP–treated mice (p < 0.05). Furthermore, AEACD attenuated the CLP challengeinduced upregulation of TNFα, IL-1β, and IL-6. Finally, AEACD inactivated TLR4/NF-κB pathway by upregulating IκBα and downregulating TLR4 and phosphorylated-p65 levels. Conclusion: AEACD administration protects mice against sepsis-induced ALI through the regulation of oxidative stress and inflammatory responses in lung tissues. The underlying mechanism occurs by inhibiting TLR4/NF-κB signaling pathway. Keywords: Aconitum carmichaelii Debeaux, Acute lung injury, Sepsis, TLR4, NF-κ

Modeling and Theoretical Analysis of GNSS-R Soil Moisture Retrieval Based on the Random Forest and Support Vector Machine Learning Approach

Global Navigation Satellite System-Reflectometry (GNSS-R) as a microwave remote sensing technique can retrieve the Earth’s surface parameters using the GNSS reflected signal from the surface. These reflected signals convey the surface features and therefore can be utilized to detect certain physical properties of the reflecting surface such as soil moisture content (SMC). Up to now, a serial of electromagnetic models (e.g., bistatic radar and Fresnel equations, etc.) are employed and solved for SMC retrieval. However, due to the uncertainty of the physical characteristics of the sites, complexity, and nonlinearity of the inversion process, etc., it is still challenging to accurately retrieve the soil moisture. The popular machine learning (ML) methods are flexible and able to handle nonlinear problems. It can dig out and model the complex interactions between input and output and ultimately make good predictions. In this paper, two typical ML methods, specifically, random forest (RF) and support vector machine (SVM), are employed for SMC retrieval from GNSS-R data of self-designed experiments (in situ and airborne). A comprehensive simulated dataset involving different types of soil is constructed firstly to represent the complex interactions between the variables (reflectivity, elevation angle, dielectric constant, and SMC) for the requirement of training ML regression models. Correspondingly, the main task of soil moisture retrieval (regression) is addressed. Specifically, the post-processed data (reflectivity and elevation angle) from sensor acquisitions are used to make predictions by these two adopted ML methods and compared with the commonly used GNSS-R retrieval method (electromagnetic models). The results show that the RF outperforms the SVM method, and it is more suitable for handling the inversion problem. Moreover, the RF regression model built by the comprehensive dataset demonstrates satisfactory accuracy and strong universality, especially when the soil type is not uniform or unknown. Furthermore, the typical task of detecting water/soil (classification) is discussed. The ML algorithms demonstrate a high potential and efficiency in SMC retrieval from GNSS-R data

Relationship between temporal dynamics of intrinsic brain activity and motor function remodeling in patients with acute BGIS

Backgroundpatients with acute basal ganglia ischemic stroke (BGIS) show changes in local brain activity represented by the amplitude of low-frequency fluctuation (ALFF), but the time-varying characteristics of this local nerve activity are still unclear. This study aimed to investigate the abnormal time-varying local brain activity of patients with acute BGIS by using the ALFF method combined with the sliding-window approach.MethodsIn this study, 34 patients with acute BGIS with motor dysfunction and 44 healthy controls (HCs) were recruited. The dynamic amplitude of low-frequency fluctuation (dALFF) was employed to detect the alterations in brain activity induced by acute BGIS patients. A two-sample t-test comparison was performed to compare the dALFF value between the two groups and a Spearman correlation analysis was conducted to assess the relationship between the local brain activity abnormalities and clinical characteristics.ResultsCompared with HCs, the activity of neurons in the left temporal pole (TP), parahippocampal gyrus (paraHIP), middle occipital gyrus (MOG), dorsolateral superior frontal gyrus (SFGdl), medial cingulate cortex (MCC), right rectus, precuneus (PCu) and right cerebellum crus1 were significantly increased in patients with BGIS. In addition, we found that there was a negative correlation (r = −0.458, p = 0.007) between the dALFF value of the right rectus and the scores of the National Institutes of Health Stroke Scale (NIHSS), and a positive correlation (r = 0.488, 0.499, p < 0.05) with the scores of the Barthel Index scale (BI) and the Fugl Meyer motor function assessment (FMA). ROC analysis results demonstrated that the area under the curves (AUC) of the right rectus was 0.880, p<0.001.ConclusionThe pattern of intrinsic brain activity variability was altered in patients with acute BGIS compared with HCs. The abnormal dALFF variability might be a potential tool to assess motor function in patients with acute BGIS and potentially inform the diagnosis of this disease

GNSS-R Soil Moisture Retrieval Based on a XGboost Machine Learning Aided Method: Performance and Validation

Global navigation satellite system (GNSS)-reflectometry is a type of remote sensing technology and can be applied to soil moisture retrieval. Until now, various GNSS-R soil moisture retrieval methods have been reported. However, there still exist some problems due to the complexity of modeling and retrieval process, as well as the extreme uncertainty of the experimental environment and equipment. To investigate the behavior of bistatic GNSS-R soil moisture retrieval process, two ground-truth measurements with dierent soil conditions were carried out and the performance of the input variables was analyzed from the mathematical statistical aspect. Moreover, the feature of XGBoost method was utilized as well. As a recently developed ensemble machine learning method, the XGBoost method just emerged for the classification of remote sensing and geographic data, to investigate the characterization of the input variables in the GNSS-R soil moisture retrieval. It showed a good correlation with the statistical analysis of ground-truth measurements. The variable contributions for the input data can also be seen and evaluated. The study of the paper provides some experimental insights into the behavior of the GNSS-R soil moisture retrieval. It is worthwhile before establishing models and can also help with understanding the underlying GNSS-R phenomena and interpreting data

MFAP3L activation promotes colorectal cancer cell invasion and metastasis

AbstractAn abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly correlates with distant metastasis in colorectal cancer (CRC), although the mechanism has yet to be explained. In this study, we observed that MFAP3L knock-down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated the cellular location and biochemical functions of MFAP3L and found that this protein was primarily localized in the nucleus of CRC cells and acted as a protein kinase. When EGFR translocated into the nucleus upon stimulation with EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic behavior of CRC cells in vitro and in vivo could be partially explained by activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we experimentally demonstrated for the first time that MFAP3L likely participates in the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that impacts CRC metastasis

Clinical significance of a point mutation in DNA polymerase beta (POLB) gene in gastric cancer.

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC

Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer.

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLBgene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC

A Point Mutation in DNA Polymerase β (POLB) Gene Is Associated with Increased Progesterone Receptor (PR) Expression and Intraperitoneal Metastasis in Gastric Cancer

Increased expression of progesterone receptor (PR) has been reported in gastric cancer (GC). We have previously identified a functional T889C point mutation in DNA polymerase beta (POLB), a DNA repair gene in GC. To provide a detailed analysis of molecular changes associated with the mutation, human cDNA microarrays focusing on 18 signal transduction pathways were used to analyze differential gene expression profiles between GC tissues with T889C mutant in POLB gene and those with wild type. Among the differentially expressed genes, notably, PR was one of the significantly up-regulated genes in T889C mutant POLB tissues, which were subsequently confirmed in POLB gene transfected AGS cell line. Interestingly, patients with T889C mutation and PR positivity were associated with higher incidence of intraperitoneal metastasis (IM). In vitro studies indicate that PR expression was upregulated in AGS cell line when transfected with T889C mutant expression vector. Cotransfection of T889C mutant allele and PR gene induced cell migration in the cell line. These data demonstrated that T889C mutation-associated PR overexpression results in increased IM. Therefore, T889C mutation-associated PR overexpression may serve as a biomarker for an adverse prognosis for human GC