Clinical significance of a new oncogenic factor P5CR1 in gastric cancer.

The article "Clinical significance of a new oncogenic factor P5CR1 in gastric cancer, by C.-X. Zhang, Y. Li, W.-H. Gong, J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24(5): 2421-2427-DOI: 10.26355/eurrev_202003_20509-PMID: 32196593" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20509.

Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7, by J. Zhang, W.-H. Gong, Y. Li, H.-Y. Zhang, C.-X. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (15): 6548-6553-DOI: 10.26355/eurrev_201908_18540-PMID: 31378895" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18540.

Clinical significance of a new oncogenic factor P5CR1 in gastric cancer.

OBJECTIVE: To explore the expression of pyrroline-5-carboxylate reductase 1 (P5CR1) and its clinical significance and function in gastric cancer (GC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot (WB) were performed to detect the expression of P5CR1 in GC tissues and normal cells. The correlation between the expression level of P5CR1 and the clinicopathological characteristics of GC patients was analyzed by the Chi-square test. Moreover, the potential of P5CR1 in predicting the postoperative prognosis of GC was assessed by Kaplan-Meier method and Log-rank test model. Clone formation, flow cytometry, scratch wound healing, and transwell assay were performed to explore the effects of P5CR1 on cell function of GC. RESULTS: The expression of P5CR1 significantly increased in GC tissues and cell lines. Its expression was significantly correlated with tumor differentiation and TNM stage of GC patients. Moreover, the GC patients with lower expression of P5CR1 had a better overall survival (OS). In univariate analyses and multivariate analyses, the expression of P5CR1 was an independent prognosis index of GC. Knockdown of P5CR1 significantly attenuated clone formation, migration, and invasion abilities, while the apoptotic rate of GC cells increased. CONCLUSIONS: P5CR1 was a novel factor involved in GC progression and constituted a potential biomarker and therapeutic target of GC.

Hsa-miR-337 inhibits non-small cell lung cancer cell invasion and migration by targeting TCF7.

OBJECTIVE: Recent studies have revealed that microRNAs (miRNAs) play a crucial role in the progression of tumorigenesis. Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. The aim of this study was to identify the exact role of hsa-miR-337 in the progression of NSCLC and to investigate the possible underlying mechanism. PATIENTS AND METHODS: Hsa-miR-337 expression in NSCLC cells and 60 paired tissue samples were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the functions of hsa-miR-337 in vitro were identified by transwell assay and wound healing assay, respectively. Furthermore, the underlying mechanism was explored by RT-qPCR, Western blot assay, and luciferase assay. RESULTS: The expression level of hsa-miR-337 in NSCLC tissues was remarkably down-regulated when compared with that of adjacent normal samples. Moreover, the invasion and migration of NSCLC cells were significantly inhibited after overexpression of hsa-miR-337 in vitro. Moreover, after overexpression of hsa-miR-337 in vitro, the mRNA and protein levels of TCF7 were significantly down-regulated. Besides, the expression of TCF7 in NSCLC tissues was negatively correlated with the expression of hsa-miR-337. CONCLUSIONS: The above results suggested that hsa-miR-337 could repress the migration and invasion of NSCLC cells through directly targeting TCF7. Furthermore, hsa-miR-337 might offer a new therapeutic intervention for NSCLC patients.

Effect of estrogen on right ventricular remodeling of monocrotaline-induced pulmonary arterial hypertension in rats and its mechanism.

OBJECTIVE: To elucidate the effect of estrogen on right ventricular remodeling of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats and its underlying mechanism. MATERIALS AND METHODS: Male Sprague- Dawley (SD) rats were adaptively fed for one week, and then, randomly divided into control group, MCT group, MCT+17-ß estradiol (50 mg·kg-1·d-1) group, and MCT+17-ß estradiol (100 mg·kg-1·d-1) group, with 8 rats in each group. PAH rat model was constructed by subcutaneous injection of 60 mg·kg-1 MCT for consecutive 4 weeks. The right external jugular vein was intubated to monitor rat RVSP (right ventricular systolic pressure) and mPAP (mean pulmonary arterial pressure). After animal procedures, RV (right ventricle) and LV+S (left ventricle+ventricular septum) of rat were harvested and weighed. Rat tibia was collected and recorded for its length, followed by calculation of RV/(LV+S) and RV/length of the tibia. HE staining and Masson staining were conducted to observe the pathological change and collagen deposition in RV, respectively. RV was prepared for homogenate, followed by detection of total antioxidant capacity (T-AOC) and malondialdehyde (MDA) activities. Expression levels of collagen I, collagen III, NOX4, and NF-κB in RV of PAH rats were detected by qRT-PCR and Western blot. RESULTS: Lower RVSP, mPAP, RV/(LV+S) and RV/length of the tibia were observed in rats of MCT+17-ß estradiol (50 mg·kg-1·d-1) group and MCT+17-ß estradiol (100 mg·kg-1·d-1) group compared with those of MCT group. Injection of 17-ß estradiol (50 mg·kg-1·d-1 and 100 mg·kg-1·d-1) in PAH rats remarkably alleviated pathological changes and collagen deposition in RV. T-AOC activity increased, whereas MDA activity decreased in PAH rats injected with 17-ß estradiol. Expression levels of collagen I, collagen III, NOX4, and NF-κB in RV of PAH rats were all downregulated by 17-ß estradiol treatment. CONCLUSIONS: 17-ß estradiol could remarkably alleviate MCT-induced right ventricular remodeling of PAH rats. It is suggested that 17-ß estradiol exerts its protective role in PAH by inhibiting NOX4-mediated oxidative stress and NF-κB-mediated collagen deposition.

[Forensic Investigation in Han Population by SiFa™ 23 Plex Kit （Beta Version）].

OBJECTIVES: To investigate the performance of SiFa™ 23 Plex Kit （beta version） and its population genetics of STR loci in Han population. METHODS: Genotyping was performed for 1 000 unrelated healthy Han individuals by the kit. The efficiency of the kit was tested, and the frequency data and population genetics parameter information of STR loci were analysed statistically. RESULTS: The minimum amplification system could be 6.25 µL. In 25 µL standard reaction system, a satisfied genotyping profiles could be obtained with the DNA content as low as 125 pg. Among the 1 000 individuals, 267 alleles were detected by 21 autosomal STR loci of the kit, which conformed to Hardy-Weinberg equilibrium. Fifteen and eleven alleles were observed at the newly added STR loci D1S1656 and D10S1248, respectively, which showed a high polymorphism information content. CONCLUSIONS: SiFa™ 23 Plex Kit （beta version） is excellent in testing blood samples. Its accuracy, repeatability and sensitivity can satisfy the need of forensic practice, which makes it be applied to forensic-related case work and DNA database establishment.

The inhibitory effect of resveratrol on COX-2 expression in human colorectal cancer: a promising therapeutic strategy.

OBJECTIVE: The objective of this study is to investigate the mechanism of resveratrol (RSVL) on the inhibitory effect on the expression of COX-2 in human colorectal cancer. MATERIALS AND METHODS: In this study, we used the HCT-116 cells as the observation group, and the normal cells as the control group. The inhibitory effect induced by RSVL on the COX-2 expression in human colorectal cancer was investigated. For the observation group, cells were cultured in the nutrition solution with RSVL, while the cells in both control group (normal colon epithelial cells) and blank control group (none-treated HCT-116 cells) were cultured in the regular nutrition solution. We assayed the mRNA expression and the protein expression of COX-2 in different groups using Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot methods, respectively. Also, we measured the cell growth and apoptosis in different treatment groups by using methyl thiazolyl tetrazolium assay (MTT) method, and detected the differences in COX-2 expression among different groups through immunohistochemistry staining RESULTS: Compared with blank control group, the rate of cell proliferation in the observation group treated with RSVL was significantly reduced. The results of RT-qPCR revealed that the mRNA expression of COX-2 of the observation group was affected compared with the blank control group. According to the results from enzyme-linked immunosorbent assay (ELISA) and Western blot, the expression of the COX-2 protein in the observation group treated with RSVL was significantly lower than that in the blank control group; however, results from the observation group and the control group were similar. Also, the immunohistochemistry results showed the positive rate of COX-2 expression in the observation group was significantly lower than that in the control group. CONCLUSIONS: RSVL (in a certain concentration) can suppress the human colorectal cancer through inhibition of COX-2 expression.

Marsdenia tenacissima extract sensitizes MG63 cells to doxorubicin-induced apoptosis.

Marsdenia tenacissima extract (MTE) is a new plate-derived biotechnology product that is frequently used, but occasionally reported, in the field of chemotherapy. In this study, we assessed the antitumor activity and related mechanisms of MTE by various biotechnological methods. The survival rates of MG63 osteosarcoma cells treated with MTE and doxorubicin were measured, individually or jointly, and the changes in cellular shape, apoptotic rates, and Fas expression were observed. The results indicated that combination of MTE and doxorubicin up-regulated Fas expression and induced apoptosis. The survival rate of combined application of 50 mg/mL MTE and 1 µg/mL doxorubicin was significantly lower than that of the individual application (P < 0.01). Other biotechnology methods also showed an apoptosis-inducing effect of combined application that was much stronger than individual application. All of these results suggested that MTE may promote the effects of doxorubicin chemotherapy, perhaps related to the up-regulation of Fas expression in tumor cells.

Synergistic increase in the sensitivity of osteosarcoma cells to thermochemotherapy with combination of paclitaxel and etoposide.

Osteosarcoma is a malignant bone tumor which is found most commonly in adolescents and young adults. Local perfusion thermochemotherapy has long been proposed as an alternative strategy for the treatment of osteosarcoma. As a standard anticancer drug, paclitaxel plays a significant role in the treatment of a number of tumors; however, little is known concerning its ability to promote thermochemotherapy. The aim of this study was to evaluate the cytotoxic effects of a combination of paclitaxel and etoposide on an osteosarcoma cell line in the presence of hyperthermia and to investigate the related mechanism. Our study indicated that 1 h after the application of a combination of 10 µg/ml paclitaxel and 5 µg/ml etoposide to OS732 cells at 43˚C, the survival rate of the cells was 14.52% which was significantly lower than when either 10 µg/ml paclitaxel (45.83%) or 5 µg/ml etoposide (43.31%) was applied alone (P<0.01). Moreover, changes in cellular morphology and apoptotic rates indicated that the apoptosis-inducing effect of the combination was much stronger than that of either drug applied individually. Fas expression levels in the OS732 cells were increased by the combination of paclitaxel and etoposide in the presence of hyperthermia. Therefore, paclitaxel enhances the thermochemotherapy of the osteosarcoma cell line and this is primarily accomplished by the upregulation of Fas expression and the induction of apoptosis.

Differential regulation of chemokine gene expression by 15-deoxy-delta 12,14 prostaglandin J2.

Ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), such as 15-deoxy-Delta(12,14)PGJ2 (15d-PGJ2) have been proposed as a new class of antiinflammatory compounds with possible clinical applications. As there is some controversy over the inhibitory effects of 15d-PGJ2 on chemokine gene expression, we investigated whether 15d-PGJ2 itself affected chemokine gene expression in human monocytes/macrophages and two monocytic cell lines. Here we demonstrate that the 15d-PGJ2 can induce IL-8 gene expression. In contrast, monocyte chemoattractant protein-1 gene expression was suppressed by 15d-PGJ2, while the expression of RANTES was unaltered. Furthermore, concomitant treatment of monocytes/macrophages with 15d-PGJ2 (2.5 x 10(-6) M) potentiated LPS-induced gene expression of IL-8 mRNA, but suppressed PMA-induction of IL-8 mRNA. In addition, treatment of U937 and THP-1 cells with 15d-PGJ2 also resulted in induction of IL-8 gene expression. Further studies demonstrated that 15d-PGJ2 regulated IL-8 gene expression via a ligand-specific and PPARgamma-dependent pathway. Our observations revealed a previous unappreciated function and mechanism of 15d-PGJ2-mediated regulation of cytokine gene expression in monocytes/macrophages.

Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses.

Polymorphonuclear leukocytes (PMN) are the most abundant leukocytes, comprising about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells, leading to the hypothesis that the release of PMN granular peptides may link innate and adaptive immunity. During the past several years, we have focused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approaches and have shown several key findings that support the hypothesis. The findings include the requirement for priming PMN by cytokines to induce the delayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expression of new cell-surface markers by such cytokine-activated PMN. In the present manuscript, we focus on the phenotypic and functional changes that occur during PMN activation with selected cytokines. The results of our study indicate that inflammatory PMN are heterogeneous and play roles in not only innate but also adaptive immunity in response to stimuli released in injured tissues.

Expression of CCR6 and CD83 by cytokine-activated human neutrophils.

Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-alpha was largely responsible for the PHA-sup-induced CCR6 mRNA expression. Among recombinant cytokines, TNF-alpha induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-gamma induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125-labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-alpha and IFN-gamma induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage-colony-stimulating factor, TNF-alpha, and IFN-gamma, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response. (Blood. 2000;96:3958-3963)

Role of progesterone in peripheral nerve repair.

Progesterone is synthesized in the peripheral nervous system in glial cells. The functions of progesterone are indicated by the findings that it stimulates neurite outgrowth from dorsal root ganglia sensory neurones in explant cultures, accelerates the maturation of the regenerating axons in cryolesioned sciatic nerve, and enhances the remyelination of regenerated nerve fibres. The formation of myelin sheaths around axons is a sexually dimorphic process, as the sheaths are thicker in female than in male regenerating nerves. The progesterone-induced myelination is probably mediated by progesterone receptors, as it is impaired by mifepristone (RU486), a progesterone antagonist. The stimulation of neurite growth in the peripheral nervous system may be mediated by a progesterone metabolite, 5alpha-tetrahydroprogesterone, through GABA(A) receptors.

The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.

Baicalin (BA) is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory and anti-viral activities. In order to elucidate the mechanism(s) of action of BA, we tested whether BA could interfere with chemokines or chemokine receptors, which are critical mediators of inflammation and infection. We observed that BA inhibited the binding of a number of chemokines to human leukocytes or cells transfected to express specific chemokine receptors. This was associated with a reduced capacity of the chemokines to induce cell migration. Co-injection of BA with CXC chemokine interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands. This conclusion was supported by the fact that BA cross-linked to oxime resin bound chemokines of the CXC (stromal cell-derived factor (SDF)-1alpha, IL-8), CC (macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-2), and C (lymphotactin (Ltn)) subfamilies. BA did not interact with CX3C chemokine fractalkine/neurotactin or other cytokines, such as TNF-alpha and IFN-gamma, indicating that its action is selective. These results suggest that one possible anti-inflammatory mechanism of BA is to bind a variety of chemokines and limit their biological function.

T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor.

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. The peptide segment T20/DP178, located in the C-terminus of the ectodomain of gp41, interacts with the N-terminal leucine zipper-like domain on gp41 to establish the fusogenic conformation of the virus. Synthetic T20/DP178 peptide is highly efficacious in inhibiting HIV-1 infection in vitro by disrupting the transformation of fusogenic status of viral gp41; thus, it has been proposed for clinical trial. We report that synthetic T20/DP178 is a chemoattractant and activator of human peripheral blood phagocytes but not of T lymphocytes. We further demonstrate that T20/DP178 specifically activates a seven-transmembrane, G-protein-coupled phagocyte receptor for N-formylated chemotactic peptides, formyl peptide receptor (FPR). Moreover, synthetic T20/DP178 analogs lacking N-terminal amino acids acted as FPR antagonists. Our results suggest that gp41 peptides regulate phagocyte function via FPR and identify a novel mechanism by which HIV-1 may modulate innate immunity.

T21/DP107, A synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors.

A leucine zipper-like domain, T21/DP107, located in the amino terminus of the ectodomain of gp41, is crucial to the formation of fusogenic configuration of the HIV-1 envelope protein gp41. We report that the synthetic T21/DP107 segment is a potent stimulant of migration and calcium mobilization in human monocytes and neutrophils. The activity of T21/DP107 on phagocytes was pertussis toxin-sensitive, suggesting this peptide uses Gi-coupled seven-transmembrane receptor(s). Since the bacterial chemotactic peptide fMLP partially desensitized the calcium-mobilizing activity of T21/DP107 in phagocytes, we postulated that T21/DP107 might preferentially use a lower affinity fMLP receptor. By using cells transfected to express cloned prototype chemotactic N-formyl peptide receptor (FPR) or its variant, FPR-like 1 (FPRL1), we demonstrate that T21/DP107 activates both receptors but has a much higher efficacy for FPRL1. In addition, T21/DP107 at nM concentrations induced migration of FPRL1-transfected human embryonic kidney 293 cells. In contrast, fMLP did not induce significant chemotaxis of the same cells at a concentration as high as 50 microM. Although a lipid metabolite, lipoxin A4, was a high-affinity ligand for FPRL1, it was not reported to induce Ca2+ mobilization or chemotaxis in FPRL1-transfected cells. Therefore, T21/DP107 is a first chemotactic peptide agonist identified thus far for FPRL1. Our results suggest that this peptide domain of the HIV-1 gp41 may have the potential to activate host innate immune response by interacting with FPR and FPRL1 on phagocytes.