Wnt/ß-catenin signalling, epithelial-mesenchymal transition and crosslink signalling in colorectal cancer cells.

Colorectal cancer (CRC), with its significant incidence and metastatic rates, profoundly affects human health. A common oncogenic event in CRC is the aberrant activation of the Wnt/ß-catenin signalling pathway, which drives both the initiation and progression of the disease. Persistent Wnt/ß-catenin signalling facilitates the epithelial-mesenchymal transition (EMT), which accelerates CRC invasion and metastasis. This review provides a summary of recent molecular studies on the role of the Wnt/ß-catenin signalling axis in regulating EMT in CRC cells, which triggers metastatic pathogenesis. We present a comprehensive examination of the EMT process and its transcriptional controllers, with an emphasis on the crucial functions of ß-catenin, EMT transcription factors (EMT-TFs). We also review recent evidences showing that hyperactive Wnt/ß-catenin signalling triggers EMT and metastatic phenotypes in CRC via "Destruction complex" of ß-catenin mechanisms. Potential therapeutic and challenges approache to suppress EMT and prevent CRC cells metastasis by targeting Wnt/ß-catenin signalling are also discussed. These include direct ß-catenin inhibitors and novel targets of the Wnt pathway, and finally highlight novel potential combinational treatment options based on the inhibition of the Wnt pathway.

[Design and application of a new transoral gastric tube for extraction and storage of gastric contents].

Difficulty in swallowing is a common symptom in stroke patients, and nasogastric tubes are routinely used to solve the nutritional support problem of these patients. The existing nasogastric tube have the disadvantages of causing aspiration pneumonia and patient discomfort. The traditional transoral gastric tube has no one-way valve switch and gastric content storage device, and cannot be fixed in the stomach, resulting in reflux of gastric contents, inability to fully understand the digestion and absorption of gastric contents, and accidental dislocation of the gastric tube, affecting further feeding and gastric content detection. For these reasons, the medical staff of the department of gastroenterology and colorectal surgery of Jilin University China-Japan Union Hospital designed a new transoral gastric tube that can extract and store gastric contents, and was granted a national utility model patent of China (ZL 2020 2 1704393.1). The device consists of collection, cannula and fixation modules. The collection module includes three parts. Gastric contents storage capsule, which can clearly visualize the gastric contents; three-way switch, which can be controlled by rotating the pathway, makes the pathway exist in different states, which is convenient for medical personnel to extract gastric juice, as well as perform intermittent oral tube feeding on the patient or close the pipeline, and reduce contamination and prolong the service life of the gastric tube; one-way valve, which can effectively avoid the contents of the reflux back into the stomach. The tube insertion module includes three parts. A graduated tube, which can enable the medical staff to effectively identify the insertion depth; a solid guide head, which makes the insertion of the tube through the mouth more smoothly; the gourd-shaped passageway, which effectively avoids the blockage of the tube. The fixation module is a water-filled balloon, which is properly filled with water and air. After the pipe is inserted through the mouth, it can be injected with water and gas properly to avoid accidental withdrawal of the gastric tube. Intermittent oroesophageal tube feeding of patients with dysphagia after stroke through a transoral gastric tube that can extract and store gastric contents can not only accelerate the recovery process of patients and shorten the hospitalization time, but also transoral enteral nutrition can effectively promote the recovery of patients' systemic systems, which has certain clinical use value.

Erratum: MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133: Erratum.

[This corrects the article DOI: 10.7150/ijbs.46822.].

Diffuse malignant peritoneal mesothelioma: A review.

Diffuse malignant peritoneal mesothelioma (DMPM) is an unusual and life-threatening locally invasive tumor. The morbidity and mortality of the disease are associated with progressive local effects in the abdominal cavity, such as abdominal distention, painful sensations, and early saturation with reduced oral intake, which eventually lead to intestinal obstruction and cachexia. Computed tomography (CT) has been widely used as a first-line diagnostic tool for DMPM. In addition, the most sensitive immunohistochemical markers of DMPM include WT 1, D2-40, and calmodulin. This paradigm has altered with the advancements in the immunohistochemical analysis of BRCA1-Associated Protein 1 (BAP1) the lack of BAP1 expression shows the diagnosis of malignancy. DMPM is resistant to conventional chemotherapies. Therefore, the gold standard for the treatment of DMPM is the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The overexpression of the phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) signaling pathway drives the malignant phenotype of DMPM, thereby showing promising potential for the treatment of DMPM. The coordinated activities among multiple RTKs are directly involved in the biological processes of DMPM, suggesting that the combined inhibition of the PI3K and mTOR signaling pathways might be an effective measure. This treatment strategy can be easily implemented in clinical practice. However, the combined inhibition of ERBB1(HER1)/ERBB2 (HER2) and ERBB3 (HER3) requires further investigations. Thus, based on these, the discovery of novel targeted therapies might be crucial to improving the prognosis of DMPM patients.

Erratum.

Colon cancer is one of the most lethal varieties of cancer. Chemotherapy remains as one of the principal treatment approaches for colon cancer. The anticancer activity of procaine (PCA), which is a local anesthetic drug, has been explored in different studies. In our study, we aimed to explore the anticancer effect of PCA on colon cancer and its underlying mechanism. The results showed that PCA significantly inhibited cell viability, increased the percentage of apoptotic cells, and decreased the expression level of RhoA in HCT116 cells in a dose-dependent manner (p<0.05 or p<0.01). Moreover, PCA increased the proportion of HCT116 cells in the G1 phase as well as downregulated cyclin D1 and cyclin E expressions (p<0.05). In addition, we found that PCA remarkably inhibited cell migration in HCT116 cells (p<0.01). However, all these effects of PCA on cell proliferation, apoptosis, and migration were significantly reversed by PCA+pc-RhoA (p<0.05 or p<0.01). PCA also significantly decreased the levels of p-ERK, p-p38MAPK, and p-FAK, but PCA+pc-RhoA rescued these effects. Furthermore, the ERK inhibitor (PD098059), p38MAPK inhibitor (SB203580), and FAK inhibitor (Y15) reversed these results. These data indicate that PCA inhibited cell proliferation and migration but promoted apoptosis as well as inactivated the ERK/MAPK/FAK pathways by regulation of RhoA in HCT116 cells.

MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133.

MiR-216a-5p has opposite effects on tumorigenesis and progression in the context of different tumors, acting as either a tumor suppressor or an oncogene. However, the expression and function of miR-216a-5p in pancreatic cancer (PC) is not well characterized. In this study, we found miR-216a-5p was significantly downregulated in PC tissues and cell lines, which showed a negative correlation with peripancreatic lymph, perineural invasion and TNM stage of PCs patients. We made use of functional assays to reveal that miR-216a-5p inhibited growth and migration of PC cells in vitro and in vivo. Then, by employing the bioinformatics analysis and luciferase reporter assay, we demonstrated TPT1 was a potential target of miR-216a-5p, which contributes to tumor malignance by mediating mTORC1 pathway-associated autophagy. Furthermore, bioinformatics analysis and RNA pulldown confirmed that miR-216a-5p was mediated by LINC01133, which sponge miR-216a-5p, as a competing endogenous RNA (ceRNA). Collectively, our study revealed an important role of LINC01133/miR-216a-5p/TPT1 axis in the genesis and progression of PCs, which provides potential biomarkers for clinical diagnosis and therapy of PCs.

MiR-135b-5p promotes viability, proliferation, migration and invasion of gastric cancer cells by targeting Krüppel-like factor 4 (KLF4).

INTRODUCTION: The expression of MiR-135b-5p was up-regulated while Krüppel-like factor 4 (KLF4) expression was extremely low in human gastric carcinoma (GC) tissues. This study aimed to explore the role of miR-135b-5p in GC cells and its influence on various cell capacity and viability by targeting KLF4. MATERIAL AND METHODS: The dual-luciferase reporter assay was first performed and the target relationship between miR-135b-5p and KLF4 was confirmed. Then three GC cell lines and the human normal gastric epithelial cell line (GES1) were analyzed for the expression level of miR-135b-5p and KLF4 mRNA by RT-qPCR. The BGC-823 GC cell line was chosen for subsequent assays. RESULTS: The expression of miR-135b-5p and KLF4 was manipulated via transfection. The changes of proliferation, invasion, migration, viability, cycle and apoptosis of GC cells were evaluated by MTS, colony formation assay, transwell assay, wound healing assay and flow cytometry assay, respectively. Overexpression of MiR-135b-5p enhanced viability, proliferation, invasion and migration of GC cells, increased cell viability and reduced cell apoptosis. Replenishing of KLF4 functioned oppositely. CONCLUSIONS: The inhibitory effects of ectopic KLF4 could be attenuated by co-transfection of miR-135b-5p. Collective data suggested that miR-135b-5p has a tumor-promoting role in GC cells via downregulating KLF4. Hence, inhibition of miR-135b-5p could be valuable for treatment of gastric cancer.

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Runx3 expression in rectal cancer cells and its effect on cell invasion and proliferation.

Effect of Runx3 gene on the cell proliferation and invasion of rectal cancer was investigated to explore potential new targets for targeted treatment of rectal cancer. The Runx3 overexpression group (OE group), blank plasmid control group, negative control and blank group of the rectal cancer HRC-9698 cell strain were set. The overexpressed Runx3 plasmid was transfected in OE group; the empty plasmid was transfected in blank plasmid control group; only liposome Lipofectamine was added to negative control group; only 1640 medium was used in blank group. RT-qPCR was used for detection of the mRNA expression of Runx3 in different groups; CCK-8 kit for detection of cell proliferation in different groups; Transwell chamber test for detection of cell strain invasion in different groups. The mRNA expression of Runx3 gene in OE group was the highest, significantly higher than that in blank plasmid control group, negative control and blank group (P<0.01). The OD values of overexpressed Runx3 at 96 h after transfection in OE group was significantly lower than each control group (P<0.01). At the same time-point, pairwise comparison in each group found that OE group was significantly lower than blank plasmid control, negative control and blank groups (all P<0.01). In the invasion experiment, the number of invasion cells in OE, blank plasmid control, negative control and blank groups were 38.63±9.33, 107.87±5.66, 110.93±4.33 and 112.86±6.66, respectively. OE group was significantly lower than each control group (P<0.01). Overexpression of Runx3 gene in vitro inhibits the cell proliferation of rectal cancer and blocks the cell invasion and metastasis. This study provides a new idea and a new molecular therapeutic target for molecular targeted therapy of rectal cancer.

Role of Leptin in Mood Disorder and Neurodegenerative Disease.

The critical regulatory role of leptin in the neuroendocrine system has been widely reported. Significantly, leptin can improve learning and memory, affect hippocampal synaptic plasticity, exert neuroprotective efficacy and reduce the risk of several neuropsychiatric diseases. In terms of depression, leptin could modulate the levels of neurotransmitters, neurotrophic factors and reverse the dysfunction in the hypothalamic-pituitary-adrenal axis (HPA). At the same time, leptin affects neurological diseases during the regulation of metabolic homeostasis. With regards to neurodegenerative diseases, leptin can affect them via neuroprotection, mainly including Alzheimer's disease and Parkinson's disease. This review will summarize the mechanisms of leptin signaling within the neuroendocrine system with respect to these diseases and discuss the therapeutic potential of leptin.

Effect of Inflammation on the Process of Stroke Rehabilitation and Poststroke Depression.

A considerable body of evidence has shown that inflammation plays an important role in the process of stroke rehabilitation and development of poststroke depression (PSD). However, the specific molecular and cellular mechanisms involved remain unclear. In this review, we summarize how neuroinflammation affects stroke rehabilitation and PSD. We mainly focus on the immune/inflammatory response, involving astrocytes, microglia, monocyte-derived macrophages, cytokines (tumor necrosis factor alpha, interleukin 1), and microRNAs (microRNA-124, microRNA 133b). This review provides new insights into the effect of inflammation on the process of stroke rehabilitation and PSD and potentially offer new therapeutic targets of stroke and PSD.

The Raman scattering of trirutile structure MgTa2O6 single crystals grown by the optical floating zone method.

Single crystals of the trirutile structure MgTa2O6 were grown via an optical floating zone method in an air atmosphere. The as-grown crystals were pale yellow and transparent and the natural cleavage plane formed during the crystal growth was determined by XRD2 to be along the c-axis direction. The variations in valence were investigated by XPS (X-ray photoelectron spectroscopy). The room-temperature axis-relative polarized Raman spectra of trirutile MgTa2O6 crystals were described. The order-disorder effect was detected via temperature-dependent Raman spectroscopy.

Phage Display Technology and its Applications in Cancer Immunotherapy.

BACKGROUND: Phage display is an effective technology for generation and selection targeting protein for a variety of purpose, which is based on a direct linkage between the displayed protein and the DNA sequence encoding it and utilized in selecting peptides, improving peptides affinity and indicating protein-protein interactions. Phage particles displaying peptide have the potential to apply in the identification of cell-specific targeting molecules, identification of cancer cell surface biomarkers, identification anti-cancer peptide, and the design of peptide-based anticancer therapy. METHOD/RESULTS: Literature searches, reviews and assessments about Phage were performed in this review from PubMed and Medline databases. CONCLUSION: The phage display technology is an inexpensive method for expressing exogenous peptides, generating unique peptides that bind any given target and investigating protein-protein interactions. Due to the powerful ability to insert exogenous gene and display exogenous peptides on the surface, phages may represent a powerful peptide delivery system that can be utilized to develop rapid, efficient, safe and inexpensive cancer therapy methods.

Pharmacological effects of berberine on mood disorders.

Berberine, a natural isoquinoline alkaloid, is used in herbal medicine and has recently been shown to have efficacy in the treatment of mood disorders. Furthermore, berberine modulates neurotransmitters and their receptor systems within the central nervous system. However, the detailed mechanisms of its action remain unclear. This review summarizes the pharmacological effects of berberine on mood disorders. Therefore, it may be helpful for potential application in the treatment of mood disorders.

The Role of KLF4 in Alzheimer's Disease.

Krüppel-like factor 4 (KLF4), a member of the family of zinc-finger transcription factors, is widely expressed in range of tissues that play multiple functions. Emerging evidence suggest KLF4's critical regulatory effect on the neurophysiological and neuropathological processes of Alzheimer's disease (AD), indicating that KLF4 might be a potential therapeutic target of neurodegenerative diseases. In this review, we will summarize relevant studies and illuminate the regulatory role of KLF4 in the neuroinflammation, neuronal apoptosis, axon regeneration and iron accumulation to clarify KLF4's status in the pathogenesis of AD.

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin.

BACKGROUND/AIMS: The present study was aimed at examining Ezrin expression in human colorectal cancer (CRC) tissues and elucidating the influence of baicalein on the proliferation of HCT116 cells. METHODS: The expression of Ezrin was determined by qRT-PCR and immunohistochemistry. HCT116 cells were divided into four groups－ baicalein groups with various concentrations, pcDNA3.1-Ezrin group, si-Ezrin group and dual inhibitory group (baicalein + si-Ezrin). CCK-8 assay and flow cytometry (FCM) were employed to assess cell proliferation and to detect the distribution of cell cycle respectively. The expression levels of Ezrin protein and cell cycle-associated proteins were detected by using western blot. The proliferation ability of CRC cells was also evaluated in vivo. RESULTS: Ezrin expression in CRC tissues was observably higher than that in adjacent colorectal tissues. With drug concentration and action time of baicalein increasing, the cell propagation capacity of HCT116 cells was decreased and the cell cycle progression was arrested. Ezrin expression was inhibited by the administration of baicalein in a dose-dependent way. The levels of CyclinD1 and CDK4 were also significantly decreased, but the expression of P53 pathway proteins P53 and P21 was markedly upregulated. CONCLUSION: Baicalein repressed proliferation of human colorectal cancer cells HCT116 and blocked cell cycle through downregulating Ezrin and upregulating P53 pathway-related proteins.

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy.

BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) of glomerular endothelial cells (GEnCs) can induce albuminuria in diabetic nephropathy. Melatonin attenuates diabetic nephropathy, but its role and mechanism in EndMT of GEnCs in diabetic nephropathy remain unknown. METHODS: The effect of melatonin on EndMT induced by transforming growth factor (TGF)-ß2 in human renal GEnCs was determined by assaying the expression of endothelial marker cells (VE-cadherin and CD31) and mesenchymal cells (α-SMA and Snail), as well as monolayer permeability. The molecular mechanism of melatonin in these processes was focused on miR-497/ROCK signaling. Furthermore, the effect and mechanism of melatonin in EndMT were confirmed in glomeruli of rats with streptozotocin-induced diabetes. RESULTS: Melatonin increased expression of VE-cadherin and CD31 and inhibited α-SMA and Snail levels that were altered by TGF-ß2 in GEnCs. Melatonin treatment reduced expression and activity of ROCK1 and ROCK2, which suppressed TGF-ß2-induced hyperpermeability of GEnCs and EndMT of GEnCs. Melatonin reduced ROCK1 and ROCK2 expression and activity in TGF-ß2-stimulated GEnCs by enhancing expression of miR-497, which targets ROCK1 and ROCK2. Furthermore, we found that melatonin inhibited EndMT in glomeruli and albuminuria in rats with streptozotocin-induced diabetes. MiR-497 expression increased, whereas ROCK1 and ROCK2 expression and activity decreased in melatonin-treated diabetic rats. CONCLUSION: Melatonin attenuated EndMT of GEnCs via regulating miR-497/ROCK signaling in diabetic nephropathy. This study improves understanding of EndMT and the role of melatonin in diabetic nephropathy.

Neural Mechanisms With Respect to Different Paradigms and Relevant Regulatory Factors in Empathy for Pain.

Empathy for pain is thought to activate the affective-motivational components of the pain matrix, which includes the anterior insula and middle and anterior cingulate cortices, as indicated by functional magnetic resonance imaging and other methodologies. Activity in this core neural network reflects the affective experience that activates our responses to pain and lays the neural foundation for our understanding of our own emotions and those of others. Furthermore, although picture-based paradigms can activate somatosensory components of directly experienced pain, cue-based paradigms cannot. In addition to this difference, the two paradigms evoke other distinct neuronal responses. Although the automatic "perception-action" model has long been the dominant theory for pain empathy, a "bottom-up, top-down" mechanism seems to be more comprehensive and persuasive. Indeed, a variety of factors can regulate the intensity of empathy for pain through "top-down" processes. In this paper, we integrate and generalize knowledge regarding pain empathy and introduce the findings from recent studies. We also present ideas for future research into the neural mechanisms underlying pain empathy.

Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases.

The amygdala is an almond-shaped nucleus located deep and medially within the temporal lobe and is thought to play a crucial role in the regulation of emotional processes. GABAergic neurotransmission inhibits the amygdala and prevents us from generating inappropriate emotional and behavioral responses. Stress may cause the reduction of the GABAergic interneuronal network and the development of neuropsychological diseases. In this review, we summarize the recent evidence investigating the possible mechanisms underlying GABAergic control of the amygdala and its interaction with acute and chronic stress. Taken together, this study may contribute to future progress in finding new approaches to reverse the attenuation of GABAergic neurotransmission induced by stress in the amygdala.