Helicobacter pylori CagA protein induces gastric cancer stem cell-like properties through the Akt/FOXO3a axis.

The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter-epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell-like properties in gastric cancer (GC) cells infected with CagA-positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self-renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs-like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA-positive GC cells infected with H. pylori exhibit CSCs-like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA-dependent manner, and our findings suggest that this activation is associated with the CSCs-like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA-dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer.

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.

Effects of bisphenol A and bisphenol analogs on the nervous system / 中华医学杂志(英文版)

Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.

Emerging role of LINC00461 in cancer.

LINC00461 is located in the intergenic region between the protein-coding genes MEF2C and TMEM161B. LINC00461 upregulation was associated with the risk of 13 tumors and was strongly associated with clinicopathologic features and poor prognosis in 11 tumors. LINC00461 is involved in resistance to four anticancer drugs, including sunitinib for renal cell carcinoma, cisplatin for head and neck squamous cell carcinoma and rectal cancer, temozolomide for glioma, and docetaxel for breast cancer. LINC00461 can sponge 18 miRNAs to form a complex ceRNA network that regulates the expression of a large number of downstream genes. LINC00461 is involved in the MAPK/ERK signaling pathway and PI3K/AKT signaling pathway, thereby promoting tumorigenesis. Notably, knockdown of LINC00461 in exosomes antagonizes tumor cell proliferation in multiple myeloma. This article summarizes the diagnostic, prognostic, and therapeutic value of LINC00461 in various tumors, and systematically describes the ceRNA network and signaling pathways associated with LINC00461, providing potential directions for future LINC00461 research.

MicroRNA-490-3p and -490-5p in carcinogenesis: Separate or the same goal?

MicroRNA (miR)-490-3p and miR-490-5p, located on chromosome 7q33, are two independent mature products of miR-490 exerting distinct effects on tumor progression. miR-490-3p and miR-490-5p possess antitumor properties. miR-490-3p dysfunction has been associated with malignancies including colorectal cancer, while the abnormal function of miR-490-5p has been more considerably associated with bladder cancer (for example). At present, there are 30 and 11 target genes of miR-490-3p and miR-490-5p, respectively, that have been experimentally verified, of which the cyclin D1 (CCND1) gene is a common target. Through these target genes, miR-490-3p and miR-490-5p are involved in 7 and 3 signaling pathways, respectively, of which only 2 are shared regulatory signaling pathways. The present review introduces two competing endogenous RNA (ceRNA) regulatory networks centered on miR-490-3p and miR-490-5p. These networks may be important promoters of tumor cell proliferation, invasiveness, metastatic potential and apoptosis. Unlike miR-490-5p, miR-490-3p plays a unique role in promoting cancer. However, both are promising molecular markers for early cancer diagnosis and prognosis. In addition, miR-490-3p was also found to be associated with the chemical resistance of cisplatin and paclitaxel. The present review focuses on the abnormal expression of miR-490-3p and miR-490-5p in different tumor types, and their complex ceRNA regulatory networks. The clinical value of miR-490-3p and miR-490-5p in cancer diagnosis, prognosis and treatment is also clarified, and an explanation for the opposing effects of miR-490-3p in tumor research is provided.

A new alkaloid from Ervatamia hainanensis / 中国中药杂志

In order to study the alkaloids from branches and leaves of Ervatamia hainanensis, silica gel, ODS, Sephadex LH-20 and HPLC chromatography were used to obtain six alkaloids from the branches and leaves of E. hainanensis with use of. Based on the physicochemical properties and spectral data, their structures were identified as 10-hydroxydemethylhirsuteine(1), 3R-hydroxycoronaridine(2), 3-(2-oxopropyl)coronaridine(3), pandine(4), 16-epi-vobasine(5), and 16-epi-vobasinic acid(6). Among them, compound 1 was a new monoterpenoid indole alkaloid, and compounds 5 and 6 were obtained from this plant for the first time.

Four new corynanthe-type alkaloids from the roots of Alstonia scholaris / 中国天然药物

Four new corynanthe-type alkaloids, meloslines C-F (1-4), together with four known ones (5-8) were isolated from the roots of Alstonia scholaris. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.

p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy.

Dihydroartemisinin (DHA) exhibits anticancer activities in a variety of cancer cells, but DHA alone are not effective enough for cancer therapy. In this study we found the stress-regulated protein p8 was obviously increased after DHA treatment in several cancer cells, which further to induce autophagy by the upregulation of endoplasmic reticulum stress-related protein ATF4 and CHOP. Furthermore, when we silenced p8 by siRNA in cancer cells, the apoptosis induced by DHA were notably increased, whereas the overexpression of p8 in cancer cells leaded to the resistance to DHA-induced apoptosis. Moreover, we found the inhibition of autophagy with chloroquine (CQ) can enhance the anticancer effect of DHA both in vitro and in vivo. In conclusion, we found that p8-mediated autophagy attenuates DHA-induced apoptosis in cancer cells, which provides evidence to support the use p8 as a cancer therapeutic target, and suggests that the combination treatment with DHA and autophagy inhibitor might be an effective cancer therapeutic strategy.

Dihydroartemisinin induces autophagy by suppressing NF-κB activation.

Nuclear factor-kappa B (NF-κB) and autophagy are two major regulators involved in both tumor initiation and progression. However, the association between these two signaling pathways still remains obscure. In this work, we demonstrate that dihydroartemisinin (DHA) stimulates the induction of autophagy in several cancer cell lines through repression of NF-κB activity. We also show that inhibiting NF-κB results in an accumulation of reactive oxygen species (ROS), which participate in the stimulation of autophagy. These findings present a pathway by which DHA promotes autophagy in cancer cells and provide evidence for the DHA-induced sensitization effect of some chemotherapeutics.

DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma.

Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1α and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials.

Hox genes from the parasitic flatworm Schistosoma japonicum.

Hox genes are characterized by a highly conserved peptide domain and contribute to antero-posterior axis patterning during embryogenesis. These genes have been widely studied in a variety of animal species due to their central role in evolutionary developmental biology. Based on the published genome assembly and unpublished re-sequencing project data, we present the first genome-wide characterization and comparative genomic analysis of the Hox gene family within Schistosoma japonicum. Eight Hox genes were identified and validated in our investigation. Phylogenetic analysis revealed that these genes are distributed among seven orthology groups of the Hox gene family. Our study further suggested that differences in the Lox5 gene copy number existed between the two closely related species, S. japonicum and Schistosoma mansoni. Semi-quantitative real-time polymerase chain reaction experiments revealed that Lox5 and Hox4 gene expression was high in the schistosomulum stage, and all four genes investigated showed highest expression within the eggs.

Changes of Muscle-related Genes and Proteins After Spaceflight in Caenorhabditis elegans / 生物化学与生物物理进展

The molecular mechanism underlying muscular atrophy and gravisensing during spaceflight is still unknown. The major effects of spaceflight on body-wall muscles of Caenorhabditis elegans (C. elegans) in the structures and functions wore examined, and five important muscle-related genes and three proteins were studied after nearly 15-day spaceflight. The changes for the wall-muscles were observed in situ. Decreased muscle fiber size was observed with myosin immunofluorescence and duller dense-body staining in flight samples, which suggested that muscular atrophy had happened during spaceflight. However, F-actin staining showed no differences between the spaceflight group and ground control group. Otherwise, after returning to the earth the C eleganu displayed reduced rate of movement with a lower ratio (height/width) in crawl trace wave, which indicated a functional defect. These results demonstrated that C. elegans muscular development was changed in response to microgravity, and changes also occurred at the level of gene transcription and protein translation. Expression of dys-I increased significantly in body-wall muscles, while hlh-1, myo-3, uric-54 and eg1-19 RNA levels decreased after spaceflight. Dystrophin (encoded by dys-1) is one of important components in dystrophin-glycoprotein complex (DGC). Increased dys-I expression after flight implied that the muscular cell would accept more gravity signals by DGC in mierogravity in order to keep mechanical balance within the cells. It is concluded that DGC was involved into the mechanical transduction in body-wall muscles of C. elegans when gravity varied, which potentially played a vital role in gravisensing. The changes ofhlh-l, myo-3, tmc-54 and egl-19 suggested that they had the effects of promoting microgravity-induced muscular atrophy in strcture and function aspects. Result of Western blotting showed that the level of myosin A in spaceflight group decreased, further confirmed that atrophy happened during flight.

Advanced Researches on Cell Adhesion Molecules of Immune System under Microgravity / 航天医学与医学工程

Returning astronauts had experienced decreased immune function and increased vulnerability to infection during spaceflights.In immune system,cell adhesion molecules(CAMs) play an important role in regulating immune response in normal physiological conditions.Studying changes of CAMs under microgravity could not only understand the effects of microgravity and its molecular mechanism on immune function,but also help to study the relative mechanism about cell sensation of microgravity.In this review,we will introduce some downstream signal pathways,gene expression and the effects on cell functions under microgravity.All of them are regulated by cell adhesion molecules related with the immune system.

Screwworm myiasis in Jamaica and proposals for its eradication

Information provided retospectively by 313 livestock producers with 61,027 animals revealed that in Jamaica in 1981 the screwworm, Cochliomyia Hominivorax (Coquerel) was prevalent throughout the island at all times of the year, but especially in the wetter periods. Pigs were the commonest host, followed in order of frequency by goats, beef cattle, horses, dairy cattle, mules and donkeys, dogs and sheep. The commonest affected wound was the umbilicus of neonates; accidental wounds, tick bites and branding scars were less often affected. The estimated annual loss due to screwworm myiasis, comprising mortality, medication and labour costs for inspection and treatment, was about J$12 million. Other losses are due to failure to thrive and reduction in milk yield. The possibility of eradicating screwworm from Jamaica is briefly discussed (AU)