Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease.

Gastric peroral endoscopic myotomy (G-POME) is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tunnel around the pyloric sphincter. In 2013, Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy, providing a new direction for the treatment of gastroparesis. With the recent and rapid development of G-POME therapy technology, progress has been made in the treatment of gastroparesis and other upper digestive tract diseases, such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture, with G-POME. This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

Clinical guideline on magnetically controlled capsule gastroscopy (2021 edition).

With the development and generalization of endoscopic technology and screening, clinical application of magnetically controlled capsule gastroscopy (MCCG) has been increasing. In recent years, various types of MCCG are used globally. Therefore, establishing relevant guidelines on MCCG is of great significance. The current guidelines containing 23 statements were established based on clinical evidence and expert opinions, mainly focus on aspects including definition and diagnostic accuracy, application population, technical optimization, inspection process, and quality control of MCCG. The level of evidence and strength of recommendations were evaluated. The guidelines are expected to guide the standardized application and scientific innovation of MCCG for the reference of clinicians.

MiR-130a-3p regulates neural stem cell differentiation in vitro by targeting Acsl4.

In the adult mammalian brain, neural stem cells (NSCs) are the precursor cells of neurons that contribute to nervous system development, regeneration, and repair. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cell fate determination and differentiation by negatively regulating gene expression. Here, we identified a post-transcriptional mechanism, centred around miR-130a-3p that regulated NSC differentiation. Importantly, overexpressing miR-130a-3p promoted NSC differentiation into neurons, whereas inhibiting miR-130a-3p function reduced the number of neurons. Then, the quantitative PCR, Western blot and dual-luciferase reporter assays showed that miR-130a-3p negatively regulated acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. Additionally, inhibition of Acsl4 promoted NSC differentiation into neurons, whereas silencing miR-130a-3p partially suppressed the neuronal differentiation induced by inhibiting Acsl4. Furthermore, overexpressing miR-130a-3p or inhibiting Acsl4 increased the levels of p-AKT, p-GSK-3ß and PI3K. In conclusion, our results suggested that miR-130a-3p targeted Acsl4 to promote neuronal differentiation of NSCs via regulating the Akt/PI3K pathway. These findings may help to develop strategies for stem cell-mediated treatment for central nervous system diseases.

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation.

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3' untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, ß-catenin, phosphor-GSK-3ß, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/ß-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

miR-33-3p Regulates PC12 Cell Proliferation and Differentiation In Vitro by Targeting Slc29a1.

MicroRNA-33-3p (miR-33-3p) has been widely investigated for its roles in lipid metabolism and mitochondrial function; however, there are few studies on miR-33-3p in the context of neurological diseases. In this study, we investigated the functional role of miR-33-3p in rat pheochromocytoma PC12 cells. A miR-33-3p mimic was transduced into PC12 cells, and its effects on proliferation, apoptosis, and differentiation were studied using the MTS assay, EdU labeling, flow cytometry, qRT-PCR, western blot, ELISA, and immunofluorescence. We found that miR-33-3p significantly suppressed PC12 cell proliferation, but had no effect on apoptosis. Furthermore, miR-33-3p promoted the differentiation of PC12 cells into Tuj1-positive and choline acetyltransferase-positive neuron-like cells. Mechanistically, miR-33-3p repressed the expression of Slc29a1 in PC12 cells. Importantly, knocking down Slc29a1 in PC12 cells inhibited proliferation and induced differentiation into neuron-like cells. In conclusion, this study showed that miR-33-3p regulated Slc29a1, which in turn controlled the proliferation and differentiation of PC12 cells. Thus, we hypothesize that the miR-33-3p/Slc29a1 axis could be a promising therapeutic target for recovering neurons and the cholinergic nervous system.

[Current status and research advances of high-temperature hazards in rice]. / æ°´ç¨»é«˜æ¸©çƒ­å®³çš„ç ”ç©¶çŽ°çŠ¶ä¸Žè¿›å±•.

High temperature stress occurs frequently in rice due to global warming. High-temperature hazard during the booting-flowering and grain-filling stages is one of the major factors limiting rice yield and quality. Here, we summarized the occurrence characteristics (identification, classification, region, and time) of high-temperature hazards, and the effects of high temperature on rice growth and development, including physiology, grain yield, and grain quality. Furthermore, we reviewed molecular biology aspects including quantitative trait locus mapping, transcriptome analysis, proteome analysis, and the monitoring, early warning, risk assessment of high-temperature hazards in rice. The defensive measures against high temperature in rice including selecting heat-resistant varieties, improving field management practices and spraying exogenous substances were intensively described. Finally, future research work on high-temperature hazards in rice was prospected to provide the scientific support for rice high-temperature defense, agricultural disaster reduction, and agricultural efficiency improvement.

Long non-coding RNA GAS5 promotes PC12 cells differentiation into Tuj1-positive neuron-like cells and induces cell cycle arrest.

Growth arrest-specific 5 (GAS5) is an anti-oncogene that has been extensively studied in tumors. However, research on GAS5 in the context of nervous system disease is rare at present. This study aimed to investigate the role of the long non-coding RNA GAS5 in rat pheochromocytoma cells (PC12 cells). GAS5-overexpressing lentivirus was transfected into PC12 cells, and expression levels of GAS5 and C-myc were detected by real-time PCR. Ratios of cells in S phase were detected by 5-ethynyl-2'-deoxyuridine. Immunohistochemical staining was used to detect the immunoreactivity of neuron microtubule markers Tuj1, doublecortin, and microtubule-associated protein 2. Apoptosis was detected by flow cytometry, while expression of acetylcholine in cells was detected by western blot assay. We found that GAS5 can promote PC12 cells to differentiate into Tuj1-positive neuron-like cells with longer processes. In addition, cell proliferation and cell cycle were significantly suppressed by GAS5, whereas it had no effect on apoptosis of PC12 cells. Our results indicate that GAS5 could increase the expression of choline acetyltransferase and acetylcholine release. Thus, we speculate that GAS5 is beneficial to the recovery of neurons and the cholinergic nervous system.

Neural differentiation of human Wharton's jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats.

Human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) have excellent proliferative ability, differentiation ability, low immunogenicity, and can be easily obtained. However, there are few studies on their application in the treatment of ischemic stroke, therefore their therapeutic effect requires further verification. In this study, hWJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion. After 4 weeks, neurological functions of the rats implanted with hWJ-MSCs were significantly recovered. Furthermore, many hWJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region. These results confirm that hWJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.

Celecoxib exhibits an anti-gastric cancer effect by targeting focal adhesion and leukocyte transendothelial migration-associated genes.

Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database. Two groups of differentially expressed genes (DEGs) were identified using limma package in R language. The criterion for GSE56807 was a false discovery rate of <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets were screened out. Subsequently, pathway enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery software (P<0.1; gene count ≥2). In addition, the protein-protein interactions (PPIs) among the overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins, Biomolecular Interaction Network Database and Human Protein Reference Database. Finally, a PPI network was visualized using Cytoscape software. A total of 137 overlapped DEGs were obtained, and DEGs with opposite regulation directions in the two datasets were significantly enriched in focal adhesion and leukocyte transendothelial migration. Subsequently, a PPI network of overlapped DEGs was constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich protein 1 (CSRP1), thrombospondin 1 (THBS1), myosin light chain 9 (MYL9), filamin A (FLNA), actinin alpha 1 (ACTN1), vinculin (VCL), laminin subunit gamma 2 (LAMC2) and claudin 1 (CLDN1)] were upregulated in GC tissues and downregulated in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects by suppressing the expression of CSRP1, THBS1, MYL9, FLNA, ACTN1, VCL, LAMC2 and CLDN1, and inhibiting leukocyte transendothelial migration and focal adhesion. However, relevant experiments are required to confirm the conclusion of the present study.

The Role of Ceramide in the Pathogenesis of Alcoholic Liver Disease.

AIMS: Ceramide is an important second messenger in the sphingomyelin signaling pathway. In this review, we will focus on the potential role of ceramide in the pathogenesis of alcoholic liver disease (ALD). METHODS: We have summarized the relevant studies and reviews about the role of ceramide in ALD. In addition, we have discussed the role of acid sphingomyelinase and protein phosphatase 2A in ALD, which are associated with ceramide and hepatic steatosis. RESULTS: Recent studies have proved that the immunoreactivity and content of ceramide were increased, both in experimental models of chronic alcohol-induced steatohepatitis and human livers with severe chronic alcohol-related liver disease. Consistent with that, the levels of protein phosphatase 2A and acid sphingomyelinase were increased. Of relevance, the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) was inhibited, which could block the fatty acid oxidation and promote its synthesis. CONCLUSIONS: It was hypothesized that ethanol promoted ceramide accumulation and increased PP2A activity by activating ASMase, which may be an important mechanism in the inhibitory effect on AMPK phosphorylation and then contributed to the progression of steatosis. ASMase, a specific mechanism of ceramide generation, was proved to be a regulator of steatosis, fibrosis, lipotoxicity and endoplasmic reticulum stress.

Stromal derived factor-1α in hippocampus radial glial cells in vitro regulates the migration of neural progenitor cells.

Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries.

Synthesis and anticancer activity of aminodihydroquinoline analogs: identification of novel proapoptotic agents.

A series of 2-aminodihydroquinoline analogs were synthesized and their in vitro cytotoxicities against metastatic breast adenocarcinoma cell line MDA-MB-231 were tested. Five out of 16 compounds exhibited promising activity and structure-activity relationship revealed major role of dialkylaminoethyl substituents on dihydroquinoline ring for the activity. Two compounds, 5f and 5h, presented cytotoxicity with IC50 values of about 2 µM when the compounds were treated to the cells without serum. The cell proliferation was inhibited mildly when the cells cultured with serum. Flow cytometry analyses showed that those compounds arrested the cells at G2/M checkpoint when the cell cycle is active while they induce apoptosis when the cell growth is restricted due to the absence of growth factors. These results suggest the two novel compounds may have anticancer activity through cell cycle arrest and pro apoptosis mechanism.

Design and synthesis of carbamate and thiocarbamate derivatives and their inhibitory activities of NO production in LPS activated macrophages.

Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure-activity relationship study of these compounds is also reported. Among these compounds, compound 12b was the most potent with 6.5 µM of IC(50). They inhibited NO production through the suppression of iNOS protein and mRNA expression and nuclear translocation of p65.

The co-transduction of Nurr1 and Brn4 genes induces the differentiation of neural stem cells into dopaminergic neurons.

Fetal brain tissue can be used in cell replacement therapy for PD (Parkinson's disease), but there is a poor donor supply of this tissue. NSCs (neural stem cells) may overcome this problem as they can be isolated and expanded in vitro. However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. In the present study, we investigated the effect of Nurr1 (nuclear receptor related factor 1), a transcription factor specific for the development and maintenance of the midbrain dopaminergic neurons on inducing the differentiation of NSCs into TH (tyrosine hydroxylase) immunoreactive dopaminergic neurons. Nonetheless, these cells exhibited an immature neuronal morphology with small cell bodies and short neurite processes, and they seldom expressed DAT (dopamine transporter), a late marker of mature dopaminergic neurons. However, forced co-expression of Nurr1 with Brn4, a member of the POU domain family of transcription factors, caused immature Nurr1-induced dopaminergic neurons to differentiate into morphologically and phenotypically more mature neurons. Thus the enriched generation of mature dopaminergic neurons by forced expression of Nurr1 with Brn4 may be of future importance in NSC-based cell replacement therapy for PD.

Inhibition of TNF-α-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes.

The pathologic processes of rheumatoid arthritis are mediated by a number of cytokines, chemokines, and matrix metalloproteinases, the expressions of which are controlled by NF-κB. This study was performed to explore the effects of a benzothiazole analog, SPA0537, on the control of the NF-κB activation pathway. We also investigated whether SPA0537 had any anti-inflammatory effects in human rheumatoid fibroblast-like synoviocytes (FLS). SPA0537 inhibited the nuclear translocation and the DNA binding of NF-κB subunits, which correlated with the inhibitory effects on IKK phosphorylation and IκBα degradation in TNF-α-stimulated rheumatoid FLS. These events further suppressed chemokine production, matrix metalloproteinase secretion, and TNF-α-induced cell proliferation. In addition, SPA0537 inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor (MCSF) and receptor activator of the NF-κB ligand (RANKL) in bone marrow macrophages. These findings suggest that SPA0537 exerts anti-inflammatory effects in rheumatoid FLS through the inhibition of the NF-κB pathway. Therefore, it may have therapeutic value for the treatment of rheumatoid arthritis.

Design, synthesis and activity of benzothiazole-based inhibitors of NO production in LPS-activated macrophages.

Series of benzothiazoles were synthesized and evaluated their inhibitory activities for NO production in lipopolysaccharide-activated macrophages. The most potent compound was the indole-containing benzothiazole 3c with 4.18µM of IC(50). The mechanistic study suggested that benzothiazoles inhibited NO production by the suppression of iNOS protein and mRNA expression. They also suppressed the expression of COX-2 through the NF-κB inactivation.

Effects of Brn-4 on the neuronal differentiation of neural stem cells derived from rat midbrain.

NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particularly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases.

Synthesis of phenylisothiourea derivatives as inhibitors of NO production in LPS activated macrophages.

A series of phenylisothioureas were synthesized as inhibitors of NO production in lipopolysaccharide-activated macrophages. We investigated the effect of lipophilic moiety and N- or S-substituents of the phenylisothioureas on the activity. Inhibitory activities of carbazole-linked phenylisothioureas were superior to the corresponding simple phenylisothiourea derivatives. Among these compounds, 12b having N-ethyl and S-isopropyl groups on phenylisothiourea moiety was the most potent in the inhibition of NO production. They inhibited NO production through the suppression of the LPS-induced translocation of p65 subunit of NF-kappaB and the followed suppression of the iNOS protein and mRNA expression.

Synthesis of azaisoflavones and their inhibitory activities of NO production in activated microglia.

A series of azaisoflavones were synthesized and their biological activities were evaluated for nitric oxide (NO) production and inducible NO synthase (iNOS) expression in BV-2 microglia cell lines. Among these compounds, compound 8d was the most potent with IC(50) 7.83 microM for inhibition of NO production. Also, compound 8d inhibited expression of iNOS in LPS-induced BV2 cells. This result suggests that compound 8d inhibited the production of NO by suppressing the expression of iNOS.

Effects of Ginkgolide on the development of NOS and AChE positive neurons in the embryonic basal forebrain.

Extract of Ginkgo biloba (EGb) has been therapeutically used for several decades to increase peripheral and cerebral blood flow so as to prevent cardiovascular and neurovascular diseases. However, the role of EGb in neuroprotective effects has received much attention recently. In this study, we investigated the effect of EGb on the development of NOS and AChE positive neurons in the rat embryonic basal forebrain. The results showed that treated with EGb, the OD of MTT staining analysis, and the numbers, the cell sizes and circumferences of NOS and AChE positive neurons were greatly promoted. These data suggest that EGb had similar effects of the neurotrophins such as NGF and BDNF in promoting the development of NOS and AChE positive neurons in the rat embryonic basal forebrain.