Raspberry ketone glucoside suppresses melanin synthesis through IL6/JAK1/STAT3 signal pathway.

OBJECTIVE: This study aimed to evaluate the anti-melanogenic activity of raspberry ketone glucoside (RKG) and further explore the specific molecular mechanisms by which RKG affects melanogenesis. MATERIALS AND METHODS: The B16F10 cells model, the mushroom tyrosinase model and the zebrafish model were used to assess the whitening activity of RKG. We subsequently identified possible pathways related to RKG inhibition of melanogenesis by RNA-seq analysis and qRT-PCR on the zebrafish model, and further explored the effects of key genes on the pathway on the melanogenic effect of RKG by using related pathway inhibitors and Tg [mpeg: EGFP] transgenic zebrafish line. RESULTS: RKG could noticeably inhibit melanogenesis in B16F10 cells in vitro and on zebrafish in vivo. The RNA-Seq analysis and the qRT-PCR in zebrafish embryos indicated that the inhibition of melanogenesis by RKG could be achieved by activating JAK1/STAT3 signal pathway and inhibiting the expression levels of the MITFa, TYR, TYRP1a genes directly associated with melanogenesis. The inhibitor tests revealed that the inhibitory effect of the RKG on melanogenesis was restored by the IL6, JAK1/2, and STAT3 inhibitors, specifically STAT3 inhibitor. We further examine the relationship between the JAK1/STAT3 signal pathway and the MITFa. The achieved results indicate that the RKG could activate the zebrafish macrophages via the JAK1, but the inhibition of macrophage activation by loganin did not affect the anti-pigmentation effect of the RKG. CONCLUSIONS: RKG showed remarkable whitening activity on both B16F10 cells in vitro and zebrafish model in vivo. Furthermore, RKG could inhibit melanogenesis by activating the IL6/JAK1/STAT3 pathway, inhibiting the transcriptional activity of MITFa, and its downstream expression levels of the TYR and TYRP1a genes.

Retraction Note: Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2.

The article "Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2, by Y. Yin, Z.-F. Yang, X.-H. Li, L.-Q. Zhou, Y.-J. Zhang, B. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8560-8565-DOI: 10.26355/eurrev_201910_19171-PMID: 31646588" has been retracted by the authors as they cannot ensure the reproducibility of the data. The third party who provided some data turned out to be unreliable. The same manuscript was also questioned on PubPeer after publication. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19171.

Clinical diagnostic performance of common laboratory indicators in primary glomerulonephritis.

OBJECTIVE: Immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) are common types of primary glomerulonephritis (PGD). A lack of specific clinical features makes diagnosis difficult. Kidney function indicators have been used for their diagnosis. However, the diagnostic performance of these indicators is undetermined. The purpose of this paper is to evaluate their diagnostic potential. PATIENTS AND METHODS: 101 patients with PGD were enrolled, including 50 with MN and 51 with IgAN. The healthy controls included 110 volunteers. The indicators related to kidney function, including TP, ALB, Cre, CysC, eGFR, C1q, Ure, Anti-PLA2R, complement C3, and complement C4 in serum, ACR in urine, and antinuclear antibody profile, IgG staining, IgA staining, IgM staining, C3 staining and C1q staining in tissue samples were evaluated. RESULTS: Statistical differences were found in TP, ALB, Ure, CysC, eGFR, C1q, Anti-PLA2R, complement C3, complement C4 and ACR among the three groups of subjects. ROC analysis showed that Anti-PLA2R and ACR had the highest specificity for identifying IgAN and/or MN from the healthy controls, ACR had the highest sensitivity. The Sp and Se of IgA and IgG in tissue samples for the identification of IgAN and MN were both high. Both IgAN and MN were predicted by anti-PLA2R, especially MN. In tissue samples, MN patients were more likely to be IgG positive and IgAN patients were more likely to be IgA positive. CONCLUSIONS: IgAN and MN may be differentiated using serum Anti-PLA2R, tissue IgG, and tissue IgA. Cre is only useful in middle and late stages of GPDs, ACR is an exclusion marker, and CysC and C1q cannot be used to identify MN.

Correlation analysis of serum placental growth factor, pregnancy-related plasma protein-A and disease severity in patients with hypertensive disorder in pregnancy.

OBJECTIVE: To analyze the correlation of serum placental growth factor (PLGF), pregnancy-associated plasma protein-A (PAPP-A) and disease severity in patients with hypertensive disorders in pregnancy (HDP). PATIENTS AND METHODS: Altogether 88 pregnant women with hypertensive disorder who underwent prenatal examination and delivery in our hospital from March 2017 to February 2019 were selected and included as the research group (n=88), and 62 healthy pregnant women who underwent prenatal examination during the same period were included as the normal control group (n=62). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of PAPP-A and PLGF in the serum of the two groups. The correlation of the expression levels of PAPP-A and PLGF with the severity of HDP was analyzed. The occurrence of adverse pregnancy outcomes in the two groups was compared, and the relationship of the expression levels of PAPP-A and PLGF with adverse pregnancy outcomes was compared. RESULTS: PAPP-A expression level in serum of pregnant women in the research group was significantly higher than that in the control group, while PLGF expression level was significantly lower than that in the control group (p<0.001). PAPP-A expression level was positively correlated with HDF severity (r=0.753, p<0.001), while PLGF expression level was negatively correlated with HDP severity (r=-0.929, p<0.001). The incidence of adverse pregnancy outcomes in the research group was significantly higher than that in the control group (p<0.05). The serum PAPP-A level of patients in the group with adverse pregnancy outcomes was significantly higher than that in the group without adverse pregnancy outcomes, while PLGF level was significantly lower than that in the group without adverse pregnancy outcomes (p<0.001). CONCLUSIONS: In conclusion, the expression levels of PAPP-A and PLGF in serum were closely related to the severity of HDP and could be used as indicators for disease monitoring.

MiR-507 inhibits the growth and invasion of trophoblasts by targeting CAMK4.

OBJECTIVE: To elucidate the potential influences of miR-507 and CAMK4 on the progression of preeclampsia (PE). PATIENTS AND METHODS: Placental tissues were collected from 24 PE pregnancies and 24 healthy pregnancies. The relative levels of miR-507 and CAMK4 in placental tissues were detected. In addition, expressions of apoptosis-associated genes in collected tissues were examined by both quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The influences of miR-507 and CAMK4 on proliferative and migratory abilities in HTR-8/SVneo cells were assessed by CCK-8 and transwell assay, respectively. The target relationship between miR-507 and CAMK4 was detected by Luciferase assay. RESULTS: MiR-507 was upregulated in placental tissues collected from PE pregnancies. Overexpression of miR-507 suppressed proliferative and migratory abilities, and stimulated apoptosis in HTR-8/SVneo cells. CAMK4 was the target gene of miR-507, which was downregulated in placental tissues collected from PE pregnancies and negatively correlated to miR-507 level. The knockdown of CAMK4 suppressed proliferative and migratory abilities, and stimulated apoptosis in HTR-8/SVneo cells, and these trends were abolished by silence of miR-507. CONCLUSIONS: Highly expressed miR-507 in PE pregnancies inhibits proliferative and migratory potentials, and induces apoptosis in trophoblasts by targeting CAMK4.

MiR-526b suppresses cell proliferation, cell invasion and epithelial-mesenchymal transition in breast cancer by targeting Twist1.

OBJECTIVE: The aberrant expression of microRNAs (miRNAs) acts as crucial regulators in the tumorigenesis of breast cancer (BC). The aim of the study is to investigate the functional effects of miR-526b expression in breast cancer progression. PATIENTS AND METHODS: The expression level of miR-526b in breast cancer tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation, migration, and invasion capacity was detected by CCK-8 cell proliferation, colony formation, and transwell invasion assays after up-regulating or down-regulating miR-526b expression in breast cancer cells. Bioinformatics analysis and Dual-Luciferase reporter gene assays were used to demonstrate that Twist1 was a target of miR-526b. Western blot analysis was also performed. RESULTS: We showed that miR-526b expression was significantly downregulated in breast cancer tissues compared to adjacent normal tissues. Lower miR-526b expression was associated with lymph node metastasis in breast cancer patients. Function assays showed that upregulation of miR-526b expression suppressed cell proliferation, cell colony formation, and cell invasion ability in breast cancer. Furthermore, the upregulation of miR-526b suppressed EMT makers Vimentin expression but increased the E-cadherin expression. Mechanically, we showed that miR-526b inhibited cell EMT process by targeting Twist1 expression. CONCLUSIONS: Thus, our evidence indicated that miR-526b may serve as a potential target of breast cancer treatment.

Effect of miR-26b on gestational diabetes mellitus in rats via PI3K/Akt signaling pathway.

OBJECTIVE: The aim of this study was to explore the influence of micro ribonucleic acid (miR)-26b on gestational diabetes mellitus in rats via the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. MATERIALS AND METHODS: A total of 60 healthy pregnant female rats were randomly divided into three groups, including group A (normal group), group B (model group), and group C (model + miR-26b group). The differences in fasting blood glucose (FBG), C-reactive protein (CRP), and phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) among the three groups were analyzed via serum CRP test, morphological observation, quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), and Western blotting, respectively. RESULTS: The levels of FBG ad CRP were significantly up-regulated in group B when compared with group A (p<0.01). Meanwhile, they increased significantly in group C when compared with group B (p<0.01). Rats in group A exhibited smooth and flat thoracic aortic intimas, as well as neatly arranged smooth muscle cells at the media layer. However, rats in group B showed fractured intimas with enlarged junction gaps, as well as necrotic and detached endothelial cells. Compared with group B, group C exhibited extremely poorly arranged cells at all the layers, rough and rugged intimas, larger areas of necrotic and detached endothelial cells, and markedly worsened lesions. QRT-PCR results indicated that the expression of phosphorylated-PI3K (p-PI3K) was significantly lower in group B than that of group A (p=0.04). Meanwhile, it was markedly lower in group C than that in group B (p=0.04). The expression of p-Akt was remarkably lower in group B than group A (p=0.04), which was also significantly lower in group C than group B (p=0.04). Compared with group A, the expressions of p-PI3K and p-Akt in the thoracic aorta of group B were evidently down-regulated (p<0.01). Furthermore, they decreased markedly in group C when compared with group B (p<0.01). CONCLUSIONS: MiR-26b accelerates the progression of gestational diabetes by inhibiting the PI3K/Akt signaling pathway.

Metabolites of intestinal microflora upregulate miR-192-5p to suppress proliferation of colon cancer cells via RhoA-ROCK-LIMK2 pathway.

OBJECTIVE: The application of intestinal microflora is involved in various cancers; however, researches reporting the potential of metabolites of intestinal microflora (MIM) on biological activities of colon cancer (CC) cells are unavailable. This study was designed to testify the functions of MIM on CC cells and its mechanism. MATERIALS AND METHODS: qRT-PCR/Western blot were applied to test the expression levels of miR-192-5p and BMPR2 in human colonic epithelial cells and CC cells (HCT116, SW480). The effects of MIM, mimics-miR-192-5p or inhibitors-miR-192-5p on mRNA and protein expressions of miR-192-5p and BMPR2 were verified by qRT-PCR and Western blot. MTT assay for CC cell viability, flow cytometry for CC cells apoptosis rate, and cell scratch and cell chamber served for the analysis of invasion and migration ability of CC cells. The relationship between miR-192-5p and BMPR2 was validated employing Luciferase reporter gene assay. RESULTS: Compared with human normal colonic epithelial cells, HCT116 and SW480 cells had lower expression of miR-192-5p and higher expression of BMPR2 (p < 0.01). MIM and mimics-miR-192-5p could enhance cell apoptosis and suppress the migration and proliferation of CC cells. MIM were also found to up-regulate miR-192-5p and down-regulate the expression levels of BMPR2 and p-LIMK2 (p < 0.01). Transfection of inhibitors-miR-192-5p reversed the inhibitory effect of MIM on CC cells. CONCLUSIONS: MIM could up-regulate miR-192-5p to inhibit CC cell growth via down-regulating BMPR2 and inhibiting the activity of RhoA-ROCK-LIMK2 pathway.

Circ-ABCB10 accelerates the malignant progression of oral squamous cell carcinoma by absorbing miRNA-145-5p.

OBJECTIVE: Previous studies have confirmed the carcinogenic role of circ-ABCB10 in certain types of tumors. However, the role of circ-ABCB10 in oral squamous cell carcinoma (OSCC) has not been reported yet. This report investigated the biological function of circ-ABCB10 in aggravating the progression of OSCC by absorbing microRNA-145-5p (miRNA-145-5p) as a ceRNA. PATIENTS AND METHODS: Relative levels of circ-ABCB10 and miRNA-145-5p in OSCC tissues and cell lines were determined. The potential relation between circ-ABCB10 level and pathological indexes of OSCC patients was analyzed. Regulatory effects of circ-ABCB10 and miRNA-145-5p on proliferative and migratory capacities of CAL-27 and Tca8113 cells were assessed. The interaction between circ-ABCB10 and miRNA-145-5p was examined through dual-luciferase reporter gene assay and Chi-square test. At last, rescue experiments were carried out to uncover the role of the circ-ABCB10/miRNA-145-5p regulatory loop in regulating the progression of OSCC. RESULTS: Circ-ABCB10 was upregulated in OSCC tissues and cells. OSCC patients expressing a high level of circ-ABCB10 presented worse tumor staging and a higher rate of distant metastasis relative to those with low level. Knockdown of circ-ABCB10 attenuated proliferative and migratory capacities in CAL-27 and Tca8113 cells. Besides, miRNA-145-5p was downregulated in OSCC tissues and cells. The knockdown of miRNA-145-5p accelerated OSCC cells to proliferate and migrate. Dual-luciferase reporter gene assay proved the binding between circ-ABCB10 and miRNA-145-5p. Moreover, the miRNA-145-5p level was negatively correlated to circ-ABCB10 level in OSCC tissues. Rescue experiments indicated that miRNA-145-5p knockdown could reverse the regulatory effects of circ-ABCB10 on viability, colony formation, and migratory capacity in OSCC cells. CONCLUSIONS: Circ-ABCB10 is upregulated in OSCC, which is closely related to tumor staging and distant metastasis of OSCC patients. Circ-ABCB10 aggravates the progression of OSCC by absorbing miRNA-145-5p.

MiR-100 suppresses inflammatory activation of microglia and neuronal apoptosis following spinal cord injury via TLR4/NF-κB pathway.

OBJECTIVE: This study aims to ascertain the effect of miR-100 on inflammation, apoptosis and functional rehabilitation after spinal cord injury (SCI) and the potential mechanism. MATERIALS AND METHODS: Firstly, microglia were extracted from 3-day-old neonatal rats and cultured for the purpose of inflammatory activation. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the levels of miR-100, toll-like receptors 4 (TLR4) and nuclear factor-κB (NF-κB). Moreover, proteins expressions of I-κB and induced-nitric oxide synthase (iNOS) and apoptosis-related genes were measured by Western blotting. In addition, SCI model was established in rats. Expressions of inflammatory factors in SCI rats were determined by enzyme-linked immunosorbent assay (ELISA) assay. Expression levels of TLR4/NF-κB pathway and miR-100 were determined by qRT-PCR. Immunofluorescence was conducted to measure activated microglia. Hindlimbs motor function in SCI rats was estimated via BBB 21-point rating scale. RESULTS: In activated microglia, miR-100 level decreased, while TLR4 and NF-κB levels increased. The protein level of I-κB decreased and iNOS increased. Transfection of miR-100 mimics reversed the above trends. Inflammatory factors were highly elevated in SCI rats and mRNA levels of the TLR4/NF-κB pathway and miR-100 were down-regulated, which were ameliorated in SCI rats overexpressing miR-100 in vivo. The amount of activated microglia was declined with the administration of miR-100 mimics compared with the untreated SCI rats. Furthermore, apoptosis-related proteins were down-regulated by miR-100 mimics injection. Motor function in the miR-100 mimics group was improved better than that in the SCI group. CONCLUSIONS: MiR-100 alleviates inflammation of microglia and neuronal tissue apoptosis, and improves motor function following SCI via inhibiting the TLR4/NF-κB pathway.

Knockdown of long non-coding RNA LUCAT1 reverses high glucose-induced cardiomyocyte injury via targeting CYP11B2.

OBJECTIVE: Diabetic cardiomyopathy (DCM) is one of the major complications in patients with diabetes mellitus. Recently, long noncoding RNAs (lncRNAs) have been well concerned for their roles in the progression of multiple diseases, including DCM. In this research, we aimed to explore the role of lncRNA LUCAT1 in cardiomyocyte injury and apoptosis induced by high glucose (HG) in vitro. MATERIALS AND METHODS: High glucose-induced (HG-induced) AC16 cardiomyocytes transfected with LUCAT1 shRNA were constructed. LUCAT1 expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Subsequently, cell proliferation and cell apoptosis were detected after LUCAT1 knockdown in HG-induced AC16 cells. Moreover, RT-qPCR and Western blot assay were performed to explore the potential underlying mechanism of LUCAT1 in DCM. RESULTS: The expression of LUCAT1 was significantly upregulated in HG-treated AC16 cardiomyocytes. Moreover, knockdown of LUCAT1 could reverse cardiomyocyte injury and apoptosis through downregulating CYP11B2. CONCLUSIONS: We first demonstrated that knockdown of LUCAT1 could reverse HG-induced cardiomyocyte injury by down-regulating CYP11B2. Our findings might offer a new direction for interpreting the mechanism of DCM development.

TLR4 promotes liver inflammation by activating the JNK pathway.

OBJECTIVE: Drug-induced liver injury has become a serious public health problem that cannot be ignored. Although the mechanism of acetaminophen (APAP)-induced liver injury has been investigated for several decades, there are still many deficiencies. However, only a deeper study of its mechanism can provide more effective measures of prevention and treatment for APAP-induced liver injury. The aim of this study was to investigate whether toll-like receptor 4 (TLR4) participates in and regulates APAP-induced liver injury, which may provide a new direction for the prevention and treatment of clinical drug-induced hepatitis. MATERIALS AND METHODS: WT mice were treated with APAP (300 mg/kg) or equivalent PBS. The livers of mice were taken at 1 h, 3 h, 6 h and 12 h after treatment. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect TLR4 mRNA expression level in the liver. After TLR4 involving in APAP-induced liver injury was confirmed, we investigated the relationship between TLR4 expression and hepatic inflammation. WT and TLR4-/- mice received APAP (3000 mg/kg) intraperitoneal injection after 16 h of fasting; serum was collected after 8 h and 24 h, and serum alanine aminotransferase (ALT) and reduced glutathione (GSH) activity were measured. Rat liver tissue was observed for histological changes by hematoxylin and eosin (H&E) staining. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) assay were performed to analyze proinflammatory cytokines expression (such as TNF-α, IL-1ß, MCP-1, IL-6). After isolating mononuclear cells (MNCs) in the liver of mice, flow cytometry was used to detect cell activation level and infiltration of macrophages and neutrophils. Western blotting was used to analyze the activation of phosphorylated JNK and p38 signaling pathways in livers of WT and TLR4-/- mice. In addition, after stimulated with APAP, the silence of TLR4 in RAW264.7 cells could activate phosphorylated JNK and p38 signaling pathways. RESULTS: After APAP stimulation, WT mice exhibited more severe liver injury than TLR4-/- mice, with higher ALT levels, lower GSH levels, and more necrotic or apoptotic cells. TLR4-/- mice have lower levels of inflammatory cytokines including MCP-1 and IL-6; at the same time, the number of infiltrating macrophages and neutrophils in liver tissue of TLR4-/- mice was significantly lower than that of WT mice. The activation of JNK signaling pathway was strikingly enhanced in WT mice treated with APAP, but no significant difference was observed in the activation of JNK phosphorylation in TLR4-/- mice after the same dose of APAP stimulation. Similarly, in RAW264.7 cells, the activation of phosphorylated JNK and p38 was remarkably inhibited by TLR4-siRNA, but was activated in the control group, which was consistent in vivo. CONCLUSIONS: APAP-treated TLR4-/- mice showed milder liver injury compared to WT mice. It was confirmed that TLR4 could activate the JNK signaling pathway to induce the secretion of inflammatory factors and the infiltration of macrophages to promote APAP-induced liver injury. This finding might provide a new prevention and treatment idea for clinical drug-induced hepatitis.

MiR-431 is a prognostic marker and suppresses cell growth, migration and invasion by targeting NOTCH2 in melanoma.

OBJECTIVE: Aberrantly expressed microRNAs (miRNAs) are comprehensively involved in oncogenesis. A tumor-associated miRNA, miR-431, has been shown to play a functional effect in several tumors. However, the studies on the effects of miR-431 in melanoma were limited. The present study aimed to determine the levels of miR-431 in melanoma and to explore its clinical significance and potential function in melanoma carcinogenesis. PATIENTS AND METHODS: Aberrant miRNAs in melanoma tissues were studied via miRNA microarray. MiR-431 expression in melanoma cell lines and carcinomas tissues were detected using RT-PCR. The clinical data were interpreted by the Chi-square test, Kaplan-Meier analysis, and multivariate analysis. The cell count kit (CCK-8) assay, flow cytometry wound healing, and transwell assays were used to assess the possible influence of miR-431 on tumor ability. The potential targets of miRNA-431 were predicted using an online tool and demonstrated by the use of dual luciferase assay and Western blot analysis. RESULTS: We observed that miR-431 expression was down-regulated in melanoma cells and tumor tissues, and reduced miR-431 levels were related to ulceration and tumor stage. The survival data revealed that melanoma patients with lower miR-431 suffered poorer overall survival. Multivariate analysis confirmed that miR-431 may be an independent prognostic marker for melanoma patients. Functional studies showed that miR-431 down-regulation inhibited melanoma growth and metastasis in vitro, while its overexpression has the opposite effects. Furthermore, we identified NOTCH2 as a direct target gene of miR-431 in melanoma cells. Besides, the restoration of NOTCH2 significantly reversed the inhibitory effects of miR-431 on melanoma cells growth and metastasis. CONCLUSIONS: Our observation suggested that miR-431 could be a new therapeutic target and prognostic marker of melanoma.

MicroRNA-124 inhibits colorectal cancer cell proliferation and suppresses tumor growth by interacting with PLCB1 and regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) is the most common malignancy for cancer-associated death. This study aimed to investigate the effects of microRNA-124 (miR-124) on tumor proliferation of CRC in vivo and in vitro. MATERIALS AND METHODS: MiR-124 mimics were synthesized and transfected into SW620 cells, which were divided into SW620, microRNA-normal control (miR-NC) and miR-124 mimics group. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine miR-124, chemokine (C-C motif) ligand-20 (CCL20), tankyrase-2 (TNKS2), phospholipase Cbeta1 (PLCB1) and Wnt4. Cell counting kit-8 (CCK-8) was employed to evaluate cell proliferation. The interaction between miR-124 and PLCB1 was tested with the Dual-Luciferase assay. Cell cycle, apoptosis and invasion were also evaluated. CRC xenograft mouse model was established and tumor size was measured. Hematoxylin and eosin (HE) was used to examine inflammation. Western blot was utilized to detect Wnt4. RESULTS: MiR-124 was over-expressed in SW620 cells, significantly reduced CCL20 and enhanced TNKS2 compared to that of the miR-NC group (p<0.05). MiR-124 might play roles by initiating PLCB1 expression. MiR-124 significantly decreased cell viability compared to the miR-NC group (p<0.05). MiR-124 regulated cell cycle and markedly induced apoptosis and inhibited cell invasion compared to the miR-NC group (p<0.05). MiR-124 significantly decreased tumor size of CRC models compared to miR-NC mice (p<0.05). MiR-124 remarkably alleviated inflammation of tumor tissues. MiR-124 markedly enhanced Wnt4 expression compared to the miR-NC group (p<0.05). CONCLUSIONS: MiR-124 inhibited tumor cell proliferation in vitro and suppressed tumor growth in vivo by interacting with PLCB1 and regulating the Wnt/ß-catenin signaling pathway.

Effects of melatonin on expressions of ß-amyloid protein and S100ß in rats with senile dementia.

OBJECTIVE: To explore the effects of melatonin (MT) on expressions of ß-amyloid protein (ß-AP) and S100ß in rats with senile dementia. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into Sham group, Model group and MT group, with 12 rats in each group. Senile dementia models were established in each group except Sham group. After modeling, rats in Model group were given tail vein injection with 0.9% sodium chloride once per day. Rats in MT group were given tail vein injection with MT once per day. Materials were collected at 40 d after the intervention. Hematoxylin-Eosin (HE) staining was adopted to observe histomorphology of hippocampal area, Western blotting to detect expressions of ß-AP and S100ß protein, and quantitative polymerase chain reaction (qPCR) to detect expressions of ß-AP mRNA and S100ß mRNA. RESULTS: Histomorphology in hippocampal area of both Model group and MT group was changed compared with that in Sham group. Histomorphology data showed that the damage in the hippocampal area in MT group was improved compared with that in Model group. Western blotting detection showed that expressions of ß-AP and S100ß in Model group and MT group were significantly increased compared with those in Sham group (p<0.05). Expressions of ß-AP and S100ß protein in MT group were significantly decreased compared with those in Model group (p<0.05). Results of qPCR revealed that expressions of ß-AP mRNA and S100ß mRNA in Model group and MT group were also significantly increased compared with those in Sham group, and there were statistically significant differences (p<0.05). Expressions of ß-AP mRNA and S100ß mRNA in MT group were significantly decreased compared with those in Model group (p<0.05). CONCLUSIONS: MT can inhibit expressions of ß-AP and S100ß protein in the hippocampal area of model rats with senile dementia, which provides leads for the future treatment of senile dementia.

MiR-30e-5p inhibits proliferation and metastasis of nasopharyngeal carcinoma cells by target-ing USP22.

OBJECTIVE: To investigate the effects of miR-30e-5p on the proliferation, invasion and migration of nasopharyngeal carcinoma (NPC) cells, as well as its underlying mechanism. PATIENTS AND METHODS: We detected the expressions of miR-30e-5p in NPC tissues, adjacent normal tissues, NPC cells (5-8F cells) and control cells (293T cells) by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The target gene of miR-30e-5p was predicted by online software and ubiquitin-specific peptidase 22 (USP22) was screened out. Luciferase reporter gene assay was performed after NPC cells were co-transfected miR-30e-5p mimics or miR-30e-5p inhibitor and mutant-type or wild-type USP22, respectively. Expressions of miR-30e-5p and USP22 in 5-8F cells were detected by qRT-PCR and Western blotting. The proliferation of 5-8F cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, and the invasion and migration abilities were detected by transwell assay. The activation of the epithelial-mesenchymal transition (EMT) was analyzed by detecting expressions of EMT-associated proteins (E-cadherin and Vimentin) in NPC cells. RESULTS: Expression level of miR-30e-5p was remarkably reduced, while USP22 expression was elevated in NPC tissues and cells compared with the controls. Molecular mechanism analysis con-firmed that miR-30e-5p could negatively regulate mRNA and protein levels of USP22 by binding to its specific sequence of 3'UTR. Subsequent experiments showed that USP22 knockdown resulting from up-regulation of miR-30e-5p could inhibit proliferation, invasion, migration, and EMT in 5-8F cells. CONCLUSIONS: MiR-30e-5p was lowly expressed in NPC by targeting USP22, suggesting that miR-30e-5p could be used as a potential therapeutic target for NPC.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression.

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. METHODS: Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. CONCLUSIONS: This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Methionine synthase A2756G polymorphism and lymphoma risk: a meta-analysis.

OBJECTIVE: The association between methionine synthase (MS) A2756G polymorphism and lymphoma risk was studied with conflicting results. The present meta-analysis aimed to investigate the overall association between MS A2756G polymorphism and lymphoma risk. MATERIALS AND METHODS: We searched PubMed and Embase databases until March 30, 2017, for articles that assessed the association between MS A2756G polymorphism and lymphoma risk. Statistical analyses were performed using the Revman 5.0 software. RESULTS: A total of 14 articles involving 4,156 cases and 6,407 controls were included in this meta-analysis. Combined analysis revealed no association between this polymorphism and lymphoma susceptibility (OR = 0.92, 95% CI: 0.74-1.16, p = 0.50 for GG vs. GA+AA). Subgroup analysis by ethnicity showed decreased lymphoma risk with the MS A2756G gene polymorphism among Caucasians in GG+GA vs. AA and G vs. A models, but not among Asians. Subgroup analysis by disease type suggested that GG homozygous and G alleles were not associated with risks of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), the subtype of NHL including the diffuse large B-cell lymphoma and follicular lymphoma. CONCLUSIONS: The results in this meta-analysis suggest no association between the MS A2756G polymorphism and lymphoma risk; however, the GG homozygous and G alleles could decrease the lymphoma risk in Caucasians.