Modulation of gut microbiota by crude gac aril polysaccharides ameliorates diet-induced obesity and metabolic disorders.

Obesity is a global health challenge that causes metabolic dysregulation and increases the risk of various chronic diseases. The gut microbiome is crucial in modulating host energy metabolism, immunity, and inflammation and is influenced by dietary factors. Gac fruit (Momordica cochinchinensis), widely consumed in Southeast Asia, has been proven to have various biological activities. However, the composition and effect of crude gac aril polysaccharides (GAP) on obesity and gut microbiota disturbed by high-fat diet (HFD) remain to be elucidated. Compositional analysis showed that GAP contains high oligosaccharides, with an average of 7-8 saccharide units. To mimic clinical obesity, mice were first made obese by feeding HFD for eight weeks. GAP intervention was performed from week 9 to week 20 in HFD-fed mice. Our results showed that GAP inhibited body weight gain, eWAT adipocyte hypertrophy, adipokine derangement, and hyperlipidemia in HFD-induced obese mice. GAP improved insulin sensitivity, impaired glucose tolerance, and hepatic steatosis. GAP modulated the gut microbiota composition and reversed the HFD-induced dysbiosis of at least 20 genera. Taken together, GAP improves metabolic health and modulates the gut microbiome to relieve obesity risk factors, demonstrating the potential of dietary GAP for treating obesity-associated disorders.

Abietane diterpenoids from Isodon amethystoides and their biological activities.

Seven undescribed abietane diterpenoids [abietamethinols A-G (1-7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1-7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 µM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 µM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 µM.

Neonatal brain inflammation enhances methamphetamine-induced reinstated behavioral sensitization in adult rats analyzed with explainable machine learning.

Neonatal brain inflammation produced by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) results in long-lasting brain dopaminergic injury and motor disturbances in adult rats. The goal of the present work is to investigate the effect of neonatal systemic LPS exposure (1 or 2 mg/kg, i.p. injection in postnatal day 5, P5, male rats)-induced dopaminergic injury to examine methamphetamine (METH)-induced behavioral sensitization as an indicator of drug addiction. On P70, subjects underwent a treatment schedule of 5 once daily subcutaneous (s.c.) administrations of METH (0.5 mg/kg) (P70-P74) to induce behavioral sensitization. Ninety-six hours following the 5th treatment of METH (P78), the rats received one dose of 0.5 mg/kg METH (s.c.) to reintroduce behavioral sensitization. Hyperlocomotion is a critical index caused by drug abuse, and METH administration has been shown to produce remarkable locomotor-enhancing effects. Therefore, a random forest model was used as the detector to extract the feature interaction patterns among the collected high-dimensional locomotor data. Our approaches identified neonatal systemic LPS exposure dose and METH-treated dates as features significantly associated with METH-induced behavioral sensitization, reinstated behavioral sensitization, and perinatal inflammation in this experimental model of drug addiction. Overall, the analysis suggests that the implementation of machine learning strategies is sensitive enough to detect interaction patterns in locomotor activity. Neonatal LPS exposure also enhanced METH-induced reduction of dopamine transporter expression and [3H]dopamine uptake, reduced mitochondrial complex I activity, and elevated interleukin-1ß and cyclooxygenase-2 concentrations in the P78 rat striatum. These results indicate that neonatal systemic LPS exposure produces a persistent dopaminergic lesion leading to a long-lasting change in the brain reward system as indicated by the enhanced METH-induced behavioral sensitization and reinstated behavioral sensitization later in life. These findings indicate that early-life brain inflammation may enhance susceptibility to drug addiction development later in life, which provides new insights for developing potential therapeutic treatments for drug addiction.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Highly Reversible Molecular Photoswitches with Transition Metal Dichalcogenides Electrodes.

The molecule-electrode coupling plays an essential role in photoresponsive devices with photochromic molecules, and the strong coupling between the molecule and the conventional electrodes leads to/ the quenching effect and limits the reversibility of molecular photoswitches. In this work, we developed a strategy of using transition metal dichalcogenides (TMDCs) electrodes to fabricate the thiol azobenzene (TAB) self-assembled monolayers (SAMs) junctions with the eutectic gallium-indium (EGaIn) technique. The current-voltage characteristics of the EGaIn/GaOx //TAB/TMDCs photoswitches showed an almost 100% reversible photoswitching behavior, which increased by ∼28% compared to EGaIn/GaOx //TAB/AuTS photoswitches. Density functional theory (DFT) calculations showed the coupling strength of the TAB-TMDCs electrode decreased by 42% compared to that of the TAB-AuTS electrode, giving rise to improved reversibility. our work demonstrated the feasibility of 2D TMDCs for fabricating SAMs-based photoswitches with unprecedentedly high reversibility.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development.

BACKGROUND: mRNA vaccines have been investigated in multiple tumors, but limited studies have been conducted on their use for hepatocellular carcinoma (HCC). AIM: To identify candidate mRNA vaccine antigens for HCC and suitable subpopulations for mRNA vaccination. METHODS: Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas. Genes with somatic mutations and copy number variations were identified by cBioPortal analysis. The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis. The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells (APCs). Tumor-associated antigens were overexpressed in tumors and associated with prognosis, genomic alterations, and APC infiltration. A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes. The weighted gene coexpression network analysis (WGCNA) was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines. RESULTS: AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 were identified as candidate HCC antigens for mRNA vaccine development. Four immune subtypes (IS1-IS4) and five immune gene modules of HCC were identified that were consistent in both patient cohorts. The immune subtypes showed distinct cellular and clinical characteristics. The IS1 and IS3 immune subtypes were immunologically "cold". The IS2 and IS4 immune subtypes were immunologically "hot", and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes. IS1-related modules were identified with the WGCNA algorithm. Ultimately, five hub genes (RBP4, KNG1, METTL7A, F12, and ABAT) were identified, and they might be potential biomarkers for mRNA vaccines. CONCLUSION: AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development. The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination. RBP4, KNG1, METTL7A, F12, and ABAT are potential biomarkers for mRNA vaccines.

Identification and immune landscape analysis of fatty acid metabolism genes related subtypes of gastric cancer.

Fatty acid metabolism (FAM) is associated with prognosis and immune microenvironment remodeling in many tumors. It is currently unknown how FAM affects the immunological microenvironment and prognosis of Gastric cancer (GC). Therefore, the current work aims to categorize GC samples based on the expression status of genes involved in FAM and to identify populations that might benefit from immunotherapy. In total, 50 FAM genes associated with overall survival (OS) were determined through univariate Cox proportional hazard regression analysis by mining the public TCGA and GEO databases. The GSE84437 and TCGA-STAD cohort samples were divided into two clusters using the "NMF" R package. According to the survival curve, patients in Cluster-1 showed considerably longer OS than those in Cluster-2. Patients in Cluster-1 exhibited earlier T stages, more intestinal GCs, and were older. MSI molecular subtypes were mainly distributed in Cluster-1, while GS molecular subtypes were distributed primarily in Cluster-2. There were 227 upregulated and 22 down-regulated genes (logFC > 1 or logFC < - 1, FDR < 0.05) in Cluster-2 compared with Cluster-1. One hub module (edges = 64, nodes = 12) was identified with a module score of 11.636 through Cytoscape plug-in MCODE. KEGG and GO analysis showed that the hub genes were associated with the cell cycle and cell division. Different immune cell infiltrates profile, and immune pathway enrichment existed between the subtypes. In conclusion, the current findings showed that practically all immunological checkpoint and immunoregulatory genes were elevated in patients with Cluster-2 GC, indicating that FAM subtypes may be crucial in GC immunotherapy.

Design and synthesis of oridonin derivatives as cytotoxic agents.

Oridonin is one of the ent-kaurane diterpenes that have been studied extensively for various bioactivities. In an effort to expand natural scaffold-based library as anticancer agents, we have designed and synthesised a number of novel oridonin derivatives and evaluated their bioactivities on a panel of human cancer cell lines (HCT116, A375, MCF-7, HepG2, and A549). Compound 4b bearing a 4-fluorophenyl moiety was found to be the most active compound with an IC50 value of 0.3 µM against MCF-7 cells, which was 7.4-fold more active than oridonin. This study could provide some insightful information for further synthesis of oridonin derivatives as anticancer agents.

Protective effect of ethyl ferulate against hypoxic injury in retinal cells and retinal neovascularization in an oxygen-induced retinopathy model.

BACKGROUND: Pathological neovascularization is a major cause of visual impairment in hypoxia-induced retinopathy. Ethyl ferulate (EF), the natural ester derivative of ferulic acid commonly found in Ferula and Angelica Sinensis, has been shown to exert antioxidant, neuroprotective, and anti-inflammatory properties. However, whether EF exerts a protective effect on retinal neovascularization and the underlying mechanisms are not well known. PURPOSE: The aim of the study was to investigate the effect of EF on retinal neovascularization and explore its underlying molecular mechanisms. STUDY-DESIGN/METHODS: We constructed hypoxia models induced by cobalt chloride (CoCl2) in ARPE-19 cells and Rhesus choroid-retinal vascular endothelial (RF/6A) cells in vitro, as well as a retinal neovascularization model in oxygen-induced retinopathy (OIR) mice in vivo. RESULTS: In this work, we demonstrated that EF treatment inhibited hypoxia-induced vascular endothelial growth factor A (VEGFA) expression in ARPE-19 cells and abrogated hypoxia-induced tube formation in RF/6A cells. As expected, intravitreal injection of EF significantly suppressed retinal neovascularization in a dose-dependent manner in OIR retinas. We also found that hypoxia increased VEGFA expression by blocking autophagic flux, whereas EF treatment enhanced autophagic flux, thereby reducing VEGFA expression. Furthermore, EF activated the sequestosome 1 (p62) / nuclear factor E2-related factor 2 (Nrf-2) pathway via upregulating oxidative stress-induced growth inhibitor 1 (OSGIN1) expression, thus alleviating oxidative stress and reducing VEGFA expression. CONCLUSION: As a result of our findings, EF has an inhibitory effect on retinal neovascularization, implying a potential therapeutic strategy for hypoxia-induced retinopathy.

Precise Differentiation of Wobble-Type Allele via Ratiometric Design of a Ligase Chain Reaction-Based Electrochemical Biosensor for CYP2C19*2 Genotyping of Clinical Samples.

Due to the comparable stability between the perfect-base pair and the wobble-base pair, a precise differentiation of the wobble-type allele has remained a challenge, often leading to false results. Herein, we proposed a ligase chain reaction (LCR)-based ratiometric electrochemical DNA sensor, namely, R-eLCR, for a precise typing of the wobble-type allele, in which the traditionally recognized "negative" signal of wobble-base pair-mediated amplification was fully utilized as a "positive" one and a ratiometric readout mode was employed to ameliorated the underlying potential external influence and improved its detection accuracy in the typing of the wobble-type allele. The results showed that the ratio between current of methylene blue (IMB) and current of ferrocene (IFc) was partitioned in three regions and three types of wobble-type allele were thus precisely differentiated (AA homozygote: IMB/IFc > 2; GG homozygote: IMB/IFc < 1; GA heterozygote: 1 < IMB/IFc < 2); the proposed R-eLCR successfully discriminated the three types of CYP2C19*2 allele in nine cases of human whole blood samples, which was consistent with those of the sequencing method. These results evidence that the proposed R-eLCR can serve as an accurate and robust alternative for the identification of wobble-type allele, which lays a solid foundation and holds great potential for precision medicine.

Long-term survival of patients with hepatocellular carcinoma with hepatic, pulmonary, peritoneal and rare colon metastasis: A case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant cancer that often metastasizes and has a poor prognosis. Gastrointestinal tract metastases are rare, and colon metastases are even rarer. The long-term survival of patients with multiple intrahepatic and extrahepatic metastases, especially to the colon, has not been previously reported. CASE SUMMARY: We present an atypical clinical case of a patient with liver, right lung, peritoneal, and colon metastases diagnosed successively following hepatic resection for primary HCC. Comprehensive treatment, including partial liver, lung and colon resection, palliative management such as systemic chemotherapy, trans-arterial chemoembolization, targeted therapy with sorafenib, and cryotherapy were attempted. Despite his early metastases, the patient remained relatively healthy for 8 years after diagnosis. CONCLUSION: This case indicates that comprehensive treatment is beneficial for certain patients with metastatic HCC. Clinicians should be alert as to the possibility of rare site metastatic tumors that may be easily misdiagnosed as primary tumors.

Discovery and verification of bitter components in Panax notoginseng based on the integrated strategy of pharmacophore model, system separation and bitter tracing technology.

Panax notoginseng is a world-renowned tonic herb, which has been used as a characteristic food in Southwest China for hundreds of years. However, the taste of Panax notoginseng is extremely bitter and serious after tasting, and its bitter components are unknown. This manuscript proposes a new strategy for discovering bitter components of Panax notoginseng based on the integrated analysis of pharmacophore model, system separation and bitter tracing technology. Firstly, 16 potential bitter components were obtained by UPLC-Q-Orbitrap HRMS combined with virtual screening, most of which were saponins.Then, the bitter components were further separated by system component separation and 5 potential bitter components were obtained. Finally, the main contributors of bitterness in Panax notoginseng were verified to be Ginsenoside Rg1, Ginsenoside Rb1 and Ginsenoside Rd by components knock-in and fNIRS. In general, this paper is the first literature report on the relatively systematic study of bitter components in Panax notoginseng.

Concurrent chemotherapy using taxane plus cisplatin versus cisplatin alone in high-risk nasopharyngeal carcinoma patients with suboptimal response to induction chemotherapy.

Background: Detectable Epstein-Barr virus (EBV) DNA levels and unsatisfactory tumor response to induction chemotherapy (IC) could be used to guide the risk-adapted treatment strategy of locoregionally advanced nasopharyngeal carcinoma (LANPC) before concurrent chemoradiotherapy. We aim to compare the efficacy and safety of concurrent chemotherapy using taxane plus cisplatin [double-agent concurrent chemotherapy (DACC) group] with those of cisplatin alone [single-agent concurrent chemotherapy (SACC) group] in high-risk LANPC. Methods: Overall, 197 LANPC patients with detectable EBV DNA or stable disease (SD) after IC were retrospectively included. Potential confounders between the DACC and SACC groups were adjusted by propensity score matching. Short-term efficacy and long-term survival were assessed in the two groups. Results: Although the objective response rate of the DACC group was marginally higher than that of the SACC group, the difference was not significant (92.7% versus 85.3%, p = 0.38). Concerning long-term survival, DACC did not show superiority to SACC after patient matching: 3-year progression-free survival: 87.8% versus 81.7%, p = 0.80; overall survival: 97.6% versus 97.3%, p = 0.48; distant metastasis-free survival: 87.8% versus 90.5%, p = 0.64, and; locoregional relapse-free survival: 92.3% versus 86.9%, p = 0.77. The incidence of grade 1-4 hematological toxicities was significantly higher in the DACC group. Conclusion: Due to the small sample size, we do not have sufficient evidence that concurrent chemotherapy using taxane plus cisplatin provides additional survival benefits in LANPC patients with an unfavorable response (detectable EBV DNA levels or SD) after IC. But concurrent taxane and cisplatin chemotherapy is associated with a higher rate of hematologic adverse events. Further clinical trials will be required to establish evidence and identify more effective treatment modalities for high-risk LANPC patients.

Clinical usefulness of the lymphocyte-to-monocyte ratio and aggregate index of systemic inflammation in patients with esophageal cancer: a retrospective cohort study.

BACKGROUND: Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value. AIM: To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients. METHODS: A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan-Meier and restricted cubic spline (RCS). RESULTS: Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan-Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk. CONCLUSION: AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC.

Bioactive icetexane and abietane diterpenes from Isodon phyllopodus.

A new icetexane diterpenoid, 11, 12, 20α-trihydroxyl-7ß-methoxyicetexa-8, 11, 13-triene-19, 10-lactone [Phyllane A (1)], and a new abietane diterpenoid, 7ß, 20-epoxy-3ß, 17-acetoxy-abieta-8, 11, 13-teriene-11, 12-diol [phyllane B (2)], along with two known compounds (3 and 4) were isolated from the methanol (MeOH) extract of twigs and leaves of the folk medicinal Isodon phyllopodus. Their structures were determined by spectroscopic analyses including 2 D NMR spectral data, and further confirmed by X-ray single crystal diffraction. Moreover, the compounds were evaluated for their cytotoxicity and anti-HIV activities, and phyllane A showed anti-HIV activity with an IC50 value of 15.7 µM, but phyllane B was found to be cytotoxic to the A549 host cells with a CC50 value of 108.5 µM.

Electrochemical immunosensor based on AuNPs/ERGO@CNT nanocomposites by one-step electrochemical co-reduction for sensitive detection of P-glycoprotein in serum.

P-glycoprotein (P-gp), a transmembrane glycoprotein widely expressed on the surface of various cells, is highly associated with multidrug resistance (MDR) that heralds the malignant progress of disease after drug treatment. Notably, there have been reported that serum P-gp is a potential marker for assessing the progression of disease resistance. Currently, there are few methods for point-of-care serum P-gp detection. In this study, we proposed a gold nanoparticles/electrochemically reduced graphene oxide@carbon nanotube (AuNPs/ERGO@CNT) modified immunosensor based on a one-step electrochemical co-reduction method. The limit of detection (LOD) of our constructed electrochemical immunosensor for P-gp detection reached 0.13 ng/mL, and the detection results in serum were consistent with ELISA. The developed immunosensor is expected to provide a scientific basis for the clinical application of serum P-gp monitoring and integrated medicine.

[Main spicy components, mechanism and masking technology for spicy flavor of Chinese medicine: a review].

Many Chinese medicinal materials, vegetable oils and extracts, and even Chinese patent medicines are spicy, which influences the medication compliance of patients, especially children. Different from the sour, sweet, bitter, salty, and umami tastes, it is a painful sensation formed when the spicy substances stimulate the nerve endings. At the moment, there are a few studies on the spicy components and mechanism and masking technology for the spicy flavor of Chinese medicine in the pharmaceutical industry, and the findings in food science are usually taken as a reference, which fail to guide the masking of the spicy flavor in Chinese medicine preparations. According to literature research, the exterior-releasing medicine, dampness-resolving medicine, and interior-warming medicine are spicy, especially some vegetable oils and extracts. Taking Zingiberis Rhizoma and prescriptions containing this medicinal as an example, the spicy components in Chinese medicine and the structure-activity characteristics were analyzed to reveal the mechanism for the spicy flavor: spicy components activate the transient receptor potential vanilloid subfamily member 1(TRPV1). The advantages and disadvantages of separation, neutralization with sugar, and inclusion for the masking of the spicy flavor were summarized and the applicability in Chinese medicine was analyzed. Moreover, the future development direction was put forward. This study is expected to promote the development of spicy masking technology for Chinese medicine prescriptions for children.

Meta-analysis on the epidemiology of gastroesophageal reflux disease in China.

BACKGROUND: No large-scale epidemiological survey on the prevalence of gastroesophageal reflux disease (GERD) in China has been conducted. China has a large population and a complex geographical environment. It is important to understand the prevalence and spatial distribution of GERD in China. AIM: To explore the prevalence and the spatial, temporal, and population distributions of GERD in the natural Chinese population. METHODS: We searched Chinese and English databases for literature on the prevalence of GERD in the natural Chinese population. The prevalence of GERD was pooled using a random-effects meta-analysis model. Subgroup analysis was performed according to time, region, and population. We used ArcGIS software to draw statistical maps and trend analysis charts. Spatial autocorrelation analysis was carried out using Geoda software. Spearman correlation analysis was used to assess the spatial distribution relationship between GERD and upper digestive tract tumours. RESULTS: Altogether, 70 studies involving 276014 individuals from 24 provinces of China were included. The overall pooled prevalence of GERD was 8.7% (95%CI: 7.5%-9.9%) in mainland China. Over the past two decades, the prevalence of GERD in China has increased from 6.0% to 10.6%. GERD was more common in people aged 40-60, with body mass index ≥ 24, and of Uygur ethnicity. The prevalence was higher in the west and east than in the centre, and there may be a local spatial autocorrelation between the Qinghai-Tibet Plateau and the southeast. GERD was correlated with gastric (r = 0.421, P = 0.041) and oesophageal tumours (r = 0.511, P = 0.011) in spatial distribution. CONCLUSION: GERD is becoming common in China. The prevalence differs by region and population. The development of appropriate strategies for the prevention and treatment of GERD is needed.

Allyl Isothiocyanate (AITC) Induces Apoptotic Cell Death In Vitro and Exhibits Anti-Tumor Activity in a Human Glioblastoma GBM8401/luc2 Model.

Some clinically used anti-cancer drugs are obtained from natural products. Allyl isothiocyanate (AITC), a plant-derived compound abundant in cruciferous vegetables, has been shown to possess an anti-cancer ability in human cancer cell lines in vitro, including human brain glioma cells. However, the anti-cancer effects of AITC in human glioblastoma (GBM) cells in vivo have not yet been examined. In the present study, we used GBM8401/luc2 human glioblastoma cells and a GBM8401/luc2-cell-bearing animal model to identify the treatment efficacy of AITC. Here, we confirm that AITC reduced total cell viability and induced cell apoptosis in GBM8401/luc2 cells in vitro. Furthermore, Western blotting also showed that AITC induced apoptotic cell death through decreased the anti-apoptotic protein BCL-2, MCL-1 expression, increased the pro-apoptotic protein BAX expression, and promoted the activities of caspase-3, -8, and -9. Therefore, we further investigated the anti-tumor effects of AITC on human GBM8401/luc2 cell xenograft mice. The human glioblastoma GBM8401/luc2 cancer cells were subcutaneously injected into the right flank of BALB/c nude mice to generate glioblastoma xenograft mice. The animals were randomly divided into three groups: group I was treated without AITC (control); group II with 0.1 mg/day of AITC; and group III with 0.2 mg/day of AITC every 3 days for 27 days. Bodyweight, and tumor volume (size) were recorded every 3 days. Tumors exhibiting Luc2 intensity were measured, and we quantified intensity using Living Image software on days 0, 12, and 24. After treatment, tumor weight from each mouse was recorded. Tumor tissues were examined for histopathological changes using H&E staining, and we analyzed the protein levels via immunohistochemical analysis. Our results indicate that AITC significantly inhibited tumor growth at both doses of AITC due to the reduction in tumor size and weight. H&E histopathology analysis of heart, liver, spleen, and kidney samples revealed that AITC did not significantly induce toxicity. Body weight did not show significant changes in any experiment group. AITC significantly downregulated the protein expression levels of MCL-1, XIAP, MMP-9, and VEGF; however, it increased apoptosis-associated proteins, such as cleaved caspase-3, -8, and -9, in the tumor tissues compared with the control group. Based on these observations, AITC exhibits potent anti-cancer activity in the human glioblastoma cell xenograft model via inhibiting tumor cell proliferation and the induction of cell apoptosis. AITC may be a potential anti-GBM cancer drug that could be used in the future.

Multimodal Ochratoxin A-Aptasensor Using 3'-FAM-Enhanced Exonuclease I Tool and Magnetic Microbead Carrier.

Thanks to its preparatory ease, close affinity, and low cost, the aptasensor can serve as a promising substitute for antibody-dependent biosensors. However, the available aptasensors are mostly subject to a single-mode readout and the interference of unbound aptamers in solution and non-target-induced transition events. Herein, we proposed a multimodal aptasensor for multimode detection of ochratoxin A (OTA) with cross-validation using the 3'-6-carboxyfluorescein (FAM)-enhanced exonuclease I (Exo I) tool and magnetic microbead carrier. Specifically, the 3'-FAM-labeled aptamer/biotinylated-cDNA hybrids were immobilized onto streptavidin-magnetic microbeads via streptavidin-biotin interaction. With the presence of OTA, an antiparallel G-quadruplex conformation was formed, protecting the 3'-FAM labels from Exo I digestion, and then anti-FAM-horseradish peroxidase (HRP) was bound via specific antigen-antibody affinity; for the aptamers without the protection of OTA, the distal ssDNA was hydrolyzed from 3' → 5', releasing 3'-FAM labels to the solution. Therefore, the OTA was detected by analyzing the "signal-off" fluorescence of the supernatant and two "signal-on" signals in electrochemistry and colorimetry through the detection of the coating magnetic microbeads in HRP's substrate. The results showed that the 3'-FAM labels increased the activity of Exo I, producing a low background due to a more thorough digestion of unbound aptamers. The proposed multimodal aptasensor successfully detected the OTA in actual samples. This work first provides a novel strategy for the development of aptasensors with Exo I and 3'-FAM labels, broadening the application of aptamer in the multimode detection of small molecules.