Explore the vast range of titles available.

Matrix metalloproteinase 9 (MMP-9) is a type-IV collagenase that is highly expressed in breast cancer, but its exact role in tumor progression and metastasis is unclear. MMP-9 mRNA and protein expression was examined by real-time reverse transcriptase PCR and immunohistochemical staining, respectively, in 41 breast cancer specimens with matched peritumoral benign breast epithelial tissue and suspicious metastatic axillary lymph nodes. Lymph vessels were labeled with D2-40 and lymphatic microvessel density (LMVD) was calculated. Correlation of MMP-9 protein expression with clinicopathological parameters and LMVD was also evaluated. MMP-9(+) staining in breast cancer specimens (35/41, 85.4%) was higher than in matched epithelium (21/41, 51.2%; P<0.05) and lymph nodes (13/41, 31.7%; P<0.001). Higher MMP-9 mRNA expression was also detected in tumor specimens compared with matched epithelial tissues and lymph nodes (P<0.05). Elevated MMP-9 expression was correlated with lymph node metastasis and LMVD (P<0.05). MMP-9 was overexpressed in breast cancer specimens compared with peritumoral benign breast epithelium and lymph nodes. Moreover, its expression in the matched epithelium and lymph nodes was positively associated with lymph node metastasis, and its expression in lymph nodes was positively associated with lymphangiogenesis in breast cancer. Thus, MMP-9 is a potential marker for breast cancer progression.

BackgroundSurgery combined with new adjuvant chemotherapy is the primary treatment for early stage invasive and advanced stage breast cancer. Growing evidence indicates that patients with ERα-positive breast cancer show poor response to chemotherapeutics. However, ERα-mediated drug-resistant mechanisms remain unclear.MethodsLevels of WW domain-binding protein 2 (WBP2) and drug-resistant gene were determined by western blotting and RT-PCR, respectively. Cell viability was measured by preforming MTT assay. CD243 expression and apoptosis rate were evaluated by flow cytometry. Interactions of WBP2/ERα and ERα/MDR1 were detected by co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assay, respectively.ResultsThere was an intrinsic link between WBP2 and ERα in drug-resistant cancer cells. Upregulation of WBP2 in MCF7 cells increased the chemoresistance to doxorubicin, while RNAi-mediated knockdown of WBP2 in MCF7/ADR cells sensitised the cancer cells to doxorubicin. Further investigation in in vitro and in vivo models demonstrated that WBP2 expression was directly correlated with MDR1, and WBP2 could directly modulate MDR1 transcription through binding to ERα, resulting in increased chemotherapy drug resistance.ConclusionsOur finding provides a new mechanism for the chemotherapy response of ERα-positive breast tumours, and WBP2 might be a key molecule for developing new therapeutic strategies to treat chemoresistance in breast cancer patients.

Background Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease. Methods ECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested. Results The rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes ( P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status ( P < 0.05) and LMVD ( P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining ( P < 0.05). Conclusions Both ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide, which is mainly due to relapse and metastasis. Synaptophysin-like 1 (SYPL1), a member of SYP family proteins, exerts complicated functions, which prompted us to wonder whether SYPL1 contributed to HCC progress. Herein, we performed integrative experiments of quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis and immunohistochemistry (IHC), and found that SYPL1 overexpression in HCC tissues was closely correlated with several malignant clinicopathologic features of HCC. The results from IHC in serial sections of HCC tissues further indicated that SYPL1 expression was associated with epithelial-mesenchymal transition (EMT) biomarkers of HCC cells. Additionally, Kaplan-Meier survival analysis showed that SYPL1 overexpression was significantly associated with reduced overall survival (OS) (P<0.001) and disease-free survival (DFS) (P=0.002). Furthermore, univariate and multivariate Cox proportional hazards analysis identified SYPL1 as an independent prognostic factor for OS [hazard ratio (HR), 2.443, 95% confidence interval (CI), 1.429-4.177, P=0.001] and DFS (HR, 1.680, 95% CI=1.012-2.788, P=0.045) of HCC patients. Collectively, SYPL1 overexpression predicts poor prognosis of HCC and may associate with EMT of HCC cells. Therefore, SYPL1 could serve as a future novel biomarker and potential therapy target for HCC.

Gender differences in major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) patients with major depressive disorder remain unclear. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid anxiety in FEDN patients with MDD. A cross-sectional study was conducted with1718 FEDN patients with MDD. Patients' demographic and clinical data were collected and analyzed using standardized clinical evaluation forms. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depression, anxiety and psychotic symptoms, respectively. There were no gender-based differences in the comorbidity rates of MDD and anxiety disorders (male: 10.2% vs. female:12.7%, P = 0.123). The prevalence of MDD with severe anxiety symptoms in male patients was similar to that of female patients (80.8%vs. 80.1%, P = 0.749). Male MDD patients were younger, had earlier age of onset, and were less likely to be married. In both the male and female groups, HAMD scores, HAMA scores, suicide attempts, and psychotic symptoms in patients with severe anxiety symptoms were higher than those patients without severe anxiety symptoms (all p ≤ 0.001). Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts significantly predicted severe anxiety symptoms in both male and female patients with MDD, while body mass index(BMI)significantly predicted severe anxiety symptoms in MDD females only. Our study showed that there were no gender differences in the prevalence of comorbid anxiety in FEDN patients with MDD. Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women. •To the best of our knowledge, this is the first large clinical study to examine gender differences in first episode drug naïve patients of major depressive disorder with anxiety.•Our study showed that there were no gender differences in either comorbidities of MDD and anxiety disorder or the prevalence of MDD with severe anxiety symptoms.•Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women.

Nosiheptide is a prototypal thiopeptide antibiotic, containing an indole side ring in addition to its thiopeptide-characteristic macrocylic scaffold. This indole ring is derived from 3-methyl-2-indolic acid (MIA), a product of the radical S -adenosylmethionine enzyme NosL, but how MIA is incorporated into nosiheptide biosynthesis remains to be investigated. Here we report functional dissection of a series of enzymes involved in nosiheptide biosynthesis. We show NosI activates MIA and transfers it to the phosphopantetheinyl arm of a carrier protein NosJ. NosN then acts on the NosJ-bound MIA and installs a methyl group on the indole C4, and the resulting dimethylindolyl moiety is released from NosJ by a hydrolase-like enzyme NosK. Surface plasmon resonance analysis show that the molecular complex of NosJ with NosN is much more stable than those with other enzymes, revealing an elegant biosynthetic strategy in which the reaction flux is controlled by protein–protein interactions with different binding affinities. Thiopeptides such as nosiheptide are clinically-interesting antimicrobial natural products. Here the authors show the functional dissection of a series of enzymes involved in nosiheptide biosynthesis, revealing a unique biosynthetic pathway that centers on a previously-unknown carrier protein.

Cell-free systems have been used to synthesize chemicals by reconstitution of in vitro expressed enzymes. However, coexpression of multiple enzymes to reconstitute long enzymatic pathways is often problematic due to resource limitation/competition (e.g., energy) in the one-pot cell-free reactions. To address this limitation, here we aim to design a modular, cell-free platform to construct long biosynthetic pathways for tunable synthesis of value-added aromatic compounds, using ( S )-1-phenyl-1,2-ethanediol (( S )-PED) and 2-phenylethanol (2-PE) as models. Initially, all enzymes involved in the biosynthetic pathways were individually expressed by an E. coli -based cell-free protein synthesis (CFPS) system and their catalytic activities were confirmed. Then, three sets of enzymes were coexpressed in three cell-free modules and each with the ability to complete a partial pathway. Finally, the full biosynthetic pathways were reconstituted by mixing two related modules to synthesize ( S )-PED and 2-PE, respectively. After optimization, the final conversion rates for ( S )-PED and 2-PE reached 100 and 82.5%, respectively, based on the starting substrate of l -phenylalanine. We anticipate that the modular cell-free approach will make a possible efficient and high-yielding biosynthesis of value-added chemicals.

The bacterial artificial chromosome (BAC) system is widely used in isolation of large genomic fragments of interest. Construction of a routine BAC library requires several months for picking clones and arraying BACs into superpools in order to employ 4D-PCR to screen positive BACs, which might be time-consuming and laborious. The major histocompatibility complex (MHC) is a cluster of genes involved in the vertebrate immune system, and the classical avian MHC-B locus is a minimal essential one, occupying a 100-kb genomic region. In this study, we constructed a more effective reverse-4D BAC library for the golden pheasant, which first creates sub-libraries and then only picks clones of positive sub-libraries, and identified several MHC clones within thirty days. The full sequencing of a 97-kb reverse-4D BAC demonstrated that the golden pheasant MHC-B locus contained 20 genes and showed good synteny with that of the chicken. The notable differences between these two species were the numbers of class II B loci and NK genes and the inversions of the TAPBP gene and the TAP1-TAP2 region. Furthermore, the inverse TAP2-TAP1 was unique in the golden pheasant in comparison with that of chicken, turkey, and quail. The newly defined genomic structure of the golden pheasant MHC will give an insight into the evolutionary history of the avian MHC.

The number of smoking patients receiving anesthesia and surgical treatment is increasing day by day. It will be useful for medical advancement to explore whether smoking is an independent risk factor for postoperative cognitive impairment. A double‐blind, parallel, and controlled study was conducted on 112 patients who fulfilled the criteria for inclusion in this study and planned to undergo painless gastroscopy under general anesthesia. The baseline mini‐mental state examination (MMSE) scores and basic information were collected. The changes in the MMSE scores after waking up and 3 days after anesthesia were observed, and the adverse events (respiratory adverse reactions, circulatory fluctuations, and adverse reactions, drug use, etc.) were analyzed by logistic regression. The baseline level of each group is consistent, which is worth studying. The MMSE score of the smoking group after anesthesia was significantly different from that of the control group (p < 0.05), but there was no significant difference between the two groups 3 days after anesthesia. Among them, the differences in adverse events between the two groups were in terms of hiccup, postoperative cough, and SpO2 < 90% (p < 0.05). Regression analysis indicates that smoking after anesthesia leads to the occurrence of postoperative cough. Smoking is probably an independent risk factor for post‐operative cognitive dysfunction (POCD) in early postoperative patients. The purpose of this article was to explore whether smoking is an independent risk factor for postoperative cognitive impairment. A double‐blind, parallel, and controlled study was conducted on 112 patients who met the standard and planned to undergo painless gastroscopy under general anesthesia. The changes in mini‐mental state examination (MMSE) scores after waking up and 3 days after anesthesia and the adverse events were observed. The study found that in patients with chronic smoking after undergoing general anesthesia, the MMSE score would decline after they awoke, it indicated that smoking patients with traumatic stimulus in the absence of general anesthesia would display transient mild cognitive function, smoking is probably an independent risk factor for post‐operative cognitive dysfunction in early postoperative patients.