Curcumol Inhibits the Progression of Hepatocellular Carcinoma by Regulating the Expression of hsa_circ_0028861.

Background: Hsa_circ_0028861, a newly discovered serum exosome circular RNA (circRNA), is greatly reduced in the serum of patients with hepatocellular carcinoma (HCC). However, the exact role of hsa_circ_0028861 in the progression of liver cancer is still unknown. Materials and Methods: Thirty patients with HCC were enrolled in this study. Hsa_circ_0028861 expression was explored via real-time polymerase chain reaction (PCR) assay. The influence of curcumol on HCC cells were tested using CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, cell wound healing assay, and migration assay, respectively. The related mechanism was determined by Western blot. A xenograft tumor model was constructed, and mice were administrated with curcumol. Results: The expression of hsa_circ_0028861 in tumor tissues was elevated of patients with HCC and in HCC cells. Curcumol treatment decreased the expression of hsa_circ_0028861 in HCC cells. Curcumol treatment could largely suppress the viability, proliferation, and migration of HCC cells by reducing hsa_circ_0028861 expression and mediating the epithelial-mesenchymal transition (EMT) process. Curcumol also effectively restrained tumor growth in the HCC mice model. Conclusions: Curcumol exerted an inhibitory role in HCC progression by downregulating hsa_circ_0028861 expression and mediating the EMT process, which provides evidence for screening new therapeutic targets and drug therapies for HCC treatment.

MicroRNA3650 Promotes Gastric Cancer Proliferation and Migration through the PTEN/PI3K-AKT-mTOR and Hippo Pathways.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with seriously poor outcomes. Studies have shown that microRNAs (miRNAs) play an omnifarious regulatory effect in GC. However, the role of miR-3650 in the progression of GC is not well known. METHODS: In this study, miR-3650 expression and its clinical significance were determined using clinical specimens. The biological functions of miR-3650 were determined in gastric cancer cell lines through CCK-8, cell scratch, and transwell experiments. Bioinformatics predictions, combined with Western blot experiments, were employed to explore its downstream molecular targets. RESULTS: We observed that miR-3650 was overexpressed in GC specimens and most cell lines, i.e., 77.8% (MKN28, SNU1, AGS, MKN45, N87, BGC823 and SGC7901). The overexpression correlated with advanced T-stage, N-stage, M-stage, and TNM-stage. Furthermore, miR-3650 promoted the proliferation and migration of gastric cancer cells, and its overexpression promoted the PI3K-AKT-mTOR pathway and inhibited the PTEN and hippo pathways. The potassium ion signaling pathway was also involved in the biological process of miR-3650 promoting cancer. CONCLUSION: Therefore, we concluded that miR-3650/PTEN/PI3K-AKT-mTOR and miR-3650/hippo pathways are vital in the progression of GC and serve as novel targets for GC therapy.

Adaptive generalized super twisting sliding mode control for PMSMs with filtered high-gain observer.

This paper proposes a novel adaptive-gain generalized super twisting algorithm for permanent magnet synchronous motors. The stability of this algorithm is strict proof using the Lyapunov method. Both controllers of the speed-tracking loop and the current regulation loop are designed according to the proposed adaptive-gain generalized super twisting algorithm. Dynamically adjusted gains in the controllers can improve the transient performance and system's robustness while reducing chattering. A filtered high-gain observer is applied in the speed-tracking loop to estimate the lumped disturbances, including parameter uncertainties and external load torque disturbances. The estimates feeding forward to the controller further improve the robustness of the system. Meanwhile, the linear filtering subsystem reduces the sensitivity of the observer to the measurement noise. Finally, experiments are constructed using the adaptive gain generalized super twisting sliding mode algorithm and the fixed gain one, showing the effectiveness and advantages of the proposed control scheme.

Construction of a competing endogenous RNA network and identification of potential regulatory axes in gastric cancer chemoresistance.

BACKGROUND: Emerging evidence highlights the multifunctional role of noncoding RNAs (ncRNAs) in gastric cancer (GC) chemoresistance. However, the comprehensive expression profile and competing endogenous RNAs (ceRNAs) regulatory network of GC chemoresistance remain unanswered. METHODS: The whole-transcriptome sequencing (RNA sequencing) was performed to comprehensively analyze the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in cisplatin-resistant cells MGC-803/DDP and GC cells MGC-803. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions implicated with the DEncRNAs. Then, the cisplatin-resistant-related ceRNA network and potential regulatory axes were constructed by bioinformatic analysis. RESULTS: We successfully generated cisplatin-resistant GC cell line MGC-803/DDP. Differential expression analysis showed that a total of 1936 DElncRNAs, 2194 DEmRNAs and 174 DEmiRNAs were identified. Functional enrichment analysis indicated that those DEncRNAs were mainly involved in neuroactive ligand-receptor interaction, drug metabolism and Hippo signaling pathway. Subsequently, the cisplatin-resistant-related ceRNA network was constructed with the widely accepted vital chemo-resistant-related genes and signaling pathways. In addition, two constructed regulatory axes (include FAM66C/miR-129-5p/7 mRNAs and SFTA1P/miR-206/FN1 or NRP1) were successfully validated by the Genomic Data Commons (GDC) GC data. CONCLUSIONS: The novel ceRNA network and the potential regulatory axes may provide the most comprehensive view of GC chemoresistance to date. Our findings uncovered potential biomarkers for prognostic prediction and novel therapeutic targets for reversing cisplatin resistance in GC.

DNA barcode to trace the development and differentiation of cord blood stem cells (Review).

Umbilical cord blood transplantation was first reported in 1980. Since then, additional research has indicated that umbilical cord blood stem cells (UCBSCs) have various advantages, such as multi­lineage differentiation potential and potent renewal activity, which may be induced to promote their differentiation into a variety of seed cells for tissue engineering and the treatment of clinical and metabolic diseases. Recent studies suggested that UCBSCs are able to differentiate into nerve cells, chondrocytes, hepatocyte­like cells, fat cells and osteoblasts. The culture of UCBSCs has developed from feeder­layer to feeder­free culture systems. The classical techniques of cell labeling and tracing by gene transfection and fluorescent dye and nucleic acid analogs have evolved to DNA barcode technology mediated by transposon/retrovirus, cyclization recombination­recombinase and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR­associated protein 9 strategies. DNA barcoding for cell development tracing has advanced to include single cells and single nucleic acid mutations. In the present study, the latest research findings on the development and differentiation, culture techniques and labeling and tracing of UCBSCs are reviewed. The present study may increase the current understanding of UCBSC biology and its clinical applications.

Long non-coding RNAs and circular RNAs in tumor angiogenesis: From mechanisms to clinical significance.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) execute a wide array of functions in physiological and pathological processes, including tumor progression. Angiogenesis, an elaborate multistep process driving new blood vessel formation, accelerates cancer progression by supplying nutrients and energy. Dysregulated lncRNAs and circRNAs can reportedly impact cancer progression by influencing angiogenesis. However, the expanding landscape of lncRNAs and circRNAs in tumor progression-dependent angiogenesis remains largely unknown. This review summarizes the major functions of angiogenic lncRNAs (Angio-LncRs) and angiogenic circRNAs (termed Angio-CircRs) and their cancer mechanisms. Moreover, we highlight the commonalities of lncRNAs and circRNAs in epigenetic, transcriptional, and post-transcriptional regulation as well as illustrate how Angio-LncRs and Angio-CircRs induce cancer onset and progression. We also discuss their potential clinical applications in diagnosis, prognosis, and anti-angiogenic therapies.

Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses.

Tumor immunotherapy, especially T cell based therapy, is becoming the main force in clinical tumor therapies. Bispecific T cell engager (BiTE) uses the single chain variable fragments (scFv) of two antibodies to redirect T cells to kill target cells. BiTEs for hematologic tumors has been approved for clinical use, and BiTEs for solid tumors showed therapeutic effects in clinical trials. Oncolytic viruses (OVs) of the adenovirus expressing p53 and herpes simplex virus expressing GM-CSF was approved for clinical use in 2003 and 2015, respectively, while other OVs showed therapeutic effects in clinical trials. However, BiTE and Oncolytic virus (OV) have their own limitations. We propose that OV-BiTE has a synergistic effect on tumor immunotherapy. Feng Yu et al. designed the first OV-BiTE in 2014, which remarkably eradicated tumors in mice. Here we review the latest development of the structure, function, preclinical studies and/or clinical trials of BiTE and OV-BiTE and provide perspective views for optimizing the design of OV-BiTE. There is no doubt that OV-BiTE is becoming an exciting new platform for tumor immunotherapy and will enter clinical trial soon. Exploring the therapeutic effects and safety of OV-BiTE for synergistic tumor immunotherapy will bring new hope to tumor patients.

Raltitrexed as a synergistic hyperthermia chemotherapy drug screened in patient-derived colorectal cancer organoids.

OBJECTIVE: Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer. Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia; validate an index of the hyperthermia chemotherapy sensitization enhancement ratio (HCSER) to identify the chemotherapeutics most enhanced by hyperthermia; and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment. METHODS: Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines. Cells from both sources were encapsulated in 3D Matrigel droplets, which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres. The microspheres were seeded in 96-well plates, with each well containing a single microsphere that developed into an organoid after 7 days. The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37°C as a control and 43°C for 90 min to examine hyperthermia synergism. Cell viability was counted with 10% CCK8. RESULTS: We successfully established a library of colorectal cancer organoids from 22 patient parental tumors. We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs. In 11 of the 22 patient organoids, raltitrexed had significant hyperthermia synergism, which was indexed as the highest HCSER score within each patient group. CONCLUSIONS: Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics. We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.

The anti-endotoxic effect of o-aminobenzoic acid from Radix Isatidis.

AIM: To study the anti-endotoxic effect of o-aminobenzoic acid (OABA) isolated from Banlangen(BLG). METHODS: OABA was extracted and isolated from BLG and diluted into 0.5% solution. The concentration of endotoxin (ET) pretreated with OABA was quantitatively detected using Limulus test. The inhibition of ET-induced fever by OABA was measured in rabbits. The rates of lipopolysaccharides (LPS)-induced death in mice pretreated with or without OABA were then compared. The influence of OABA on the release of TNF-alpha and NO from macrophages induced by LPS was examined in mice. RESULTS: After pretreatment with OABA, 84.4% of ET was destroyed. The ET-induced fever in rabbits decreased significantly and the rate of LPS-induced death in mice dropped from 70% to 20%. The release of TNF-alpha and NO induced by LPS in mice was inhibited dose-dependently when the concentration of OABA was between 0.125% and 0.5%. CONCLUSION: OABA isolated from BLG has an anti-endotoxic effect.

[Studies on anti-endotoxin activity of F022 from Radix Isatidis].

OBJECTIVE: To study the anti-endotoxin activity and mechanism of F022 from Radix Isatidis. METHOD: The production of TNF-alpha and IL-6 of murine peritoneal macrophages stimulated by LPS was measured by ELISA. The temperature in rabbits was tested after i.v. administration of LPS. The lethality of BCG-primed mice was induced by LPS. RESULT: If F022 was added to macrophages culture simultaneously with LPS or 1 h before addition of LPS, production of TNF-alpha and IL-6 by macrophages was remarkably inhibited in vitro. F022 inhibited the fever induced by LPS in rabbits and protected BCG-primed mice from LPS induced lethality if given before administration of LPS. CONCLUSION: The anti-endotoxin effect of F022 may inhibit LPS binding to its receptor, and it may be a LPS receptor antagonist.