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.

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.

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.

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.

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.

A correlation study between gene polymorphism of Th cell expressed chemokine receptor CXCR3 and its ligand levels with HCV infection prognosis.

OBJECTIVE: Chemokine receptor and its ligand participate in viral immunity and HCV infection, which are important inflammatory mediators. The current study showed the different roles of Th cell secreted chemokines CXCR3, CCR5 and CCR6 in chronic liver inflammation after HCV infection. As one important chemokine receptor, the role of polypeptide property and ligand level in HCV prognosis is still unclear. This study aims to investigate gene polymorphism of chemokine genes and ligand level, and their correlation with patient liver function, to provide evidence for HCV prognosis and chronic transition mechanism. PATIENTS AND METHODS: Whole blood samples were collected. Participants were divided into chronic hepatitis, HCV cirrhosis and self-clearance groups. Chemokine level, gene polymorphism of CXCR3 gene at loci rs2280964 and liver index were measured to analyze their correlation with HCV infection or prognosis. RESULTS: Gene polymorphism of CXCR3 at loci rs22809064 is one factor-affecting prognosis of HCV patients. CG genotype at these loci is one independent risk factor affecting chronic HCV infection. IP-10, Mig and I-TAC levels were significantly elevated in chronic hepatitis group or HCV cirrhosis group (p< 0.05 compared to self-clearance group). CONCLUSIONS: Gene polymorphism at rs2280964 locus of chemokine receptor CXCR3 is one possible reason explaining differential processes of chronic transition. CXCR3 ligands IP-10, Mig and I-TAC levels were all significantly elevated in chronic hepatitis and HCV cirrhosis patients, possibly functioning as one clinical index for HCV prognosis.

LncRNA CCAT1 as the unfavorable prognostic biomarker for cholangiocarcinoma.

OBJECTIVE: To investigate the expression of long noncoding RNA CCAT1 in cholangiocarcinoma (CCA) and to assess the CCAT1 expression as a prognostic biomarker for CCA. PATIENTS AND METHODS: The CCAT1 expression in tumor tissues and paired adjacent normal tissues from 91 CCA patients was detected by quantitative real-time PCR. The association of the CCAT1 expression with clinicopathological features of CCA patients and the prognostic value of the CCAT1 expression for overall survival was also evaluated by Kaplan-Meier, Cox regression model and ROC analysis. RESULTS: The CCAT1 expression was significantly upregulated in CCA tumor tissues compared with adjacent normal tissues. The CCAT1 expression was obviously associated with histological differentiation, lymph node invasion, and TNM stage. The overall survival of CCA patients with high CCAT1 expression was worse. Furthermore, the CCAT1 expression could be considered as an independent prognostic factor in predicting the overall survival for CCA patients. CONCLUSIONS: Our study showed that lncRNA CCAT1, which was upregulated and associated with aggressive malignant behavior, may serve as a novel prognostic biomarker and potential therapeutic target for cholangiocarcinoma.

Effects of acupotomylysis on basic fibroblast growth factor and CD34 levels in rabbits with third lumbar vertebral transverse foramen syndrome.

This study observed the local tissue homogenates in rabbits with third lumbar vertebral transverse foramen syndrome and explored the mechanism of acupotomylysis in local tissue revascularization. Thirty Japanese white rabbits were randomly divided into the following 5 groups of 6 rabbits each: normal, model, acupotomy, electroacupuncture (EA), and acupotomy-EA groups. All except the normal group were comprised of animal models of third lumbar vertebral transverse foramen syndrome prepared by embedding sponge in the left third lumbar transverse process. The rabbits in the acupotomy and EA groups underwent bilateral acupotomylysis intervention; those in the acupotomy-EA group underwent acupotomylysis and EA interventions. On the 28th day after modeling, the double-antibody ELISA was used to detect b-FGF and CD34 levels in the serum and homogenates of a muscle tissue sample from the left side of the third lumbar transverse process. The b-FGF levels in local muscle homogenates were significantly higher in the modeled rabbits than in the normal rabbits (P < 0.01), and the CD34 levels in the modeled group were significantly lower than in the normal group (P < 0.01). The b-FGF and CD34 levels in the EA, acutopomy, and acutopomy-EA groups were significantly lower than those in the modeled group (P < 0.01); the CD34 levels were significantly higher in the acupotomy-EA group than in the model group (P < 0.05); and the differences among the EA, acupotomy, and acupotomy-EA groups were not significant (P > 0.05). In conclusion, acupotomylysis regulates the levels of b-FGF and CD34 levels in serum and muscle tissue as well as local tissue revascularization.

Feasibility of comfortable and secure intubation achieved with the Disposcope endoscope or Macintosh laryngoscope for patients in whom glottis viewing is difficult.

We aimed to study the feasibility of a comfortable and secure intubation achieved with the Disposcope endoscope or Macintosh laryngoscope when glottis viewing is difficult. Forty adults scheduled for elective surgery under general anesthesia, in whom glottis viewing was difficult with the Macintosh laryngoscope (classified as Cormack-Lehane Grade III or IV), were randomized into 2 groups (N = 20 each): Disposcope endoscope (Group D) and Macintosh laryngoscope (Group M). We recorded the successful glottis viewing rate; intubation time; successful intubation rate; incidence of systolic blood pressure (SBP) ≥140 mmHg and heart rate (HR) ≥90 bpm from the beginning of intubation to 5 min after intubation; and postoperative sore throat and hoarseness. Successful glottis viewing rate and successful first intubation rate were higher in Group D than in Group M (P < 0.05); the number of intubations taking >3 min and with SBP ≥140 mmHg and HR ≥90 bpm were less in Group D (P < 0.05). The visual analogue scale of postoperative sore throat 1 day after extubation was higher in Group M than in Group D (P < 0.05). No significant differences were found in other indices (P > 0.05). Better stability of hemodynamics, less intubation time, higher successful first intubation rate, and fewer incidences of postoperative sore throat were achieved in Group D than in Group M. Thus, comfortable and secure intubation can be achieved using the Disposcope endoscope in patients in whom glottis viewing is difficult.

A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.

The purpose of this study was to identify the clinical features and mutations in the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations were included in the study. All members underwent complete ophthalmic examination. Molecular genetic analysis was performed on all subjects. All exons of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences were compared with a reference database. Variations were evaluated in family members as well as 100 normal controls. Changes in structure and function of the protein induced by amino acid variation were predicted by bioinformatic analysis. Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present in all patients diagnosed with MFS. The novel heterozygous missense mutation c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not in other family members or 100 normal controls. This mutation caused an amino acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1 protein. This mutation occurred in a highly conserved region and may cause structural and functional changes in the protein according to our bioinformatic analysis. Our results suggest that the novel mutation C781W of FBN1 is responsible for the pathogenesis of MFS in this pedigree.

S100A4 expression and prognosis of gastric cancer: a meta-analysis.

The prognostic role of S100A4 in gastric cancer is still under debate. The present meta-analysis aimed to evaluate the relationship between S10A4 levels and the prognosis of gastric cancer. We performed a meta-analysis of published studies assessing the relationship between S100A4 and gastric cancer prognosis. We used the Revman 5.0 software to perform literature retrieval, article selection, data collection, and statistical analysis. A fixed-effect model was used to pool the hazard ratio (HR) and 95% confidence intervals (95%CI). A total of 7 eligible studies that included 1257 gastric cancer patients were analyzed. We did not find a prognostic value for S100A4 in gastric cancer (HR = 1.48, 95%CI = 0.77 to 2.82, P = 0.24). In conclusion, the present study indicated that S100A4 expression level is not a prognostic factor for gastric cancer.

The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury.

Receptor-interacting protein (RIP)3 is a critical regulator of necroptosis and has been demonstrated to be associated with various diseases, suggesting that its inhibitors are promising in the clinic. However, there have been few RIP3 inhibitors reported as yet. B-Raf(V600E) inhibitors are an important anticancer drug class for metastatic melanoma therapy. In this study, we found that 6 B-Raf inhibitors could inhibit RIP3 enzymatic activity in vitro. Among them, dabrafenib showed the most potent inhibition on RIP3, which was achieved by its ATP-competitive binding to the enzyme. Dabrafenib displayed highly selective inhibition on RIP3 over RIP1, RIP2 and RIP5. Moreover, only dabrafenib rescued cells from RIP3-mediated necroptosis induced by the necroptosis-induced combinations, that is, tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand or Fas ligand plus Smac mimetic and the caspase inhibitor z-VAD. Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and MLKL. Notably, RIP3 inhibition of dabrafenib appeared to be independent of its B-Raf inhibition. Dabrafenib was further revealed to prevent acetaminophen-induced necrosis in normal human hepatocytes, which is considered to be mediated by RIP3. In acetaminophen-overdosed mouse models, dabrafenib was found to apparently ease the acetaminophen-caused liver damage. The results indicate that the anticancer B-Raf(V600E) inhibitor dabrafenib is a RIP3 inhibitor, which could serve as a sharp tool for probing the RIP3 biology and as a potential preventive or therapeutic agent for RIP3-involved necroptosis-related diseases such as acetaminophen-induced liver damage.

Systematic review with meta-analysis: magnetic resonance enterography vs. computed tomography enterography for evaluating disease activity in small bowel Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has been proposed as a non-ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohn's disease (CD) with variable results. AIM: To compare the overall diagnostic accuracy in assessing the activity of small bowel and complications. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a pre-defined reference standard. Pooled sensitivity, specificity, the weighted area under the curve (AUC), incremental yield (IY) and other diagnostic indices were evaluated. RESULTS: A total of 290 CD patients from six different studies were analysed. The pooled sensitivity and specificity for MRE in detecting active small bowel CD was 87.9% [95% confidence interval (CI), 81.8-92.5] and 81.2% (95% CI: 71.9-88.4) respectively. The AUC under the summary receiver-operating characteristic (sROC) of MRE was 0.905 (SEM 0.03, standard error of the mean). Likewise, the pooled sensitivity and specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2-90.9) and 83.6% (95% CI: 75.3-90.1) with the AUC of 0.898. The AUC of MRE in detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively, compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for MRE vs. CTE was found (fixed model, P > 0.05). CONCLUSIONS: Magnetic resonance enterography has a diagnostic effectiveness comparable to computed tomography enterography, thus may serve as a radiation-free alternative for evaluation of patients with Crohn's disease.