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CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers.
We describe herein a method of recharging used commercial spin columns or assembling homemade spin columns using filter paper as binding material for cost-effective, low throughput nucleic acid purification. The efficiency of filter paper-based spin columns was evaluated for purification of nucleic acids from various sources. Following protocols of commercial kits, we found filter paper to be a useful binding material for purification of nucleic acids, including plant genomic DNA, plant total RNA, PCR products, and DNA from agarose gels. However, filter paper has a weak binding affinity to plasmid DNA in tested miniprep protocols. Protocols for the use of filter paper recharged spin columns or homemade spin columns for low throughput purification of plant genomic DNA and total RNA with unused commercial kit buffers or less expensive homemade buffers are presented.
Epidural adhesion is one of the major reasons attributed to failed back surgery syndrome after a successful laminectomy, and results in serious clinical complications which require management from physicians. Therefore, there is an urgent demand within the field to develop biodegradable anti-adhesion membranes for the prevention of post-operative adhesion.
Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs.
The effects of indigo naturalis (IN), which is a traditional Chinese herbal formulation, have been clinically demonstrated in treating refractory ulcerative colitis (UC). The present study aimed to verify the effects and mechanisms of IN in experimental UC rats. A total of 48 male Sprague-Dawley rats were randomly divided into six groups: Chow, model, high-dose IN, medium-dose IN, low-dose IN and mesalazine (a bowel-specific aminosalicylate drug) groups. The models were administered 3.5% dextran sodium sulphate solution for 7 days. The treatment groups were administered IN or mesalazine and then sacrificed and sampled on day 8. Disease activity index (DAI), histological damage score (HDS) and myeloperoxidase (MPO) activity were used to evaluate the severity of UC. Colon and serum cytokines were detected using liquid-phase chip technology and the expression of occludin protein in colonic mucosa was assessed by immunohistochemistry and western blot analysis. The results indicated that the oral administration of IN may reduce DAI, HDS and MPO activity. IN also reduced the expression of inflammatory cytokines and increased the expression of colonic mucosal repair-related cytokines and occludin protein. These results highlight the potential of IN as a therapeutic agent for treating UC through its action of inflammation control and colonic mucosal damage repair.
Infection of healthcare workers with the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.
On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital's response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin.
Cadmium (Cd) and lead (Pb) are naturally existing heavy metals that pose significant health risks. The present study aims to identify sensitive biomarkers for differentiating the toxicities induced by Cd and Pb and for providing clues for the early prediction of toxicity and environmental risk assessment. Indicators related to oxidative stress and inflammatory responses in zebrafish treated with Cd and Pb over time (from 24hpf to 96hpf) were compared. Furthermore, endpoints such as embryo lethality and teratogenicity were detected. Then, several related genes involved in oxidative stress and inflammatory responses characterizing both Cd and Pb exposure, along with key molecules in the MAPKs pathway, were compared at the mRNA level, allowing the selection of the most sensitive and informative biomarkers. Significant increases in reactive oxygen species (ROS) production were observed in zebrafish exposed to Cd and Pb. Cd and Pb exposure induced developmental toxicity, influencing survival rate, hatching rate, larval growth, and heart rate and causing abnormal embryonic development. Similar trends in SOD1 and SOD2 gene expression were induced by Cd and Pb, while nuclear factor erythroid-2 related factor 2 (Nrf2) gene expression responded differently to each metal. In addition, Cd and Pb induced a delayed activation of the CAT and HO-1 genes, with no apparent change in the 24hpf and 48hpf groups. Genes related to immunotoxicity were activated significantly in a time-dependent manner, and these genes exhibited different sensitivities to Cd and Pb. MAPKs pathway genes were also activated in a time-dependent manner, and the expression of these genes showed different effects under Cd and Pb treatment. In summary, the present works have identified some potential sensitive biomarkers. The Nrf2 gene is a potential biomarker to differentiate Pb-induced toxicity from that of Cd, and the IFN-γ gene may be used as a sensitive biomarker for evaluating the risk of Pb contamination. We found that the timeline of MAPKs pathway activation helped to differentiate these two metals toxicities. Furthermore, Pb induced the early activation of ERK2/3 and JNK1, while p38 MAPKs showed delayed activation with no apparent change in the 24hpf group. Cd induced an early activation of ERK2 and a delayed activation of p38a, p38b, ERK3 and JNK1, indicating that the JNK1 pathway is sensitive to Pb exposure, while the p38 pathway may be susceptible to Cd. This work contributes to sensitive biomarker identification and early environmental risk evaluation for chemicals as well as toxicity prediction.
BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.
Long non-coding RNAs (lncRNAs) have been reported to play essential roles in regulating the radiosensitivity of cancers. Prostate cancer-associated transcript 6 (PCAT6) exerts oncogenic roles in several tumors. However, the roles of PCAT6 and its underlying mechanism in regulating the radiosensitivity of triple-negative breast cancer (TNBC) have not been investigated.
Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF.
Vaccination is the most cost-effective medical intervention known to prevent morbidity and mortality. However, data are limited on the effectiveness of residency programs in delivering immunization knowledge and skills to trainees. The authors sought to describe the immunization competency needs of medical residents at the University of Toronto (UT), and to develop and evaluate a pilot immunization curriculum.
To evaluate retinal hard exudates (HEs) progression in patients with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) or branch retinal vascular occlusion (BRVO) after intravitreal injections of ranibizumab (IVR) treatment and identify the risk factors for the deterioration of HEs.
The fluorination strategy is one of the most efficient and popular molecular modification methods to develop new materials for organic photovoltaic (OPV) cells. For OPV materials, it is a broad agreement that fluorination can reduce the energy level and change the morphology of active layers. To explore the effect of fluorination on small molecule acceptors, we selected two non-fullerene acceptors (NFA) based bulk heterojunction (BHJ) films, involving PM6:Y6 and PM6:Y5 as model systems. The electron mobilities of the PM6:Y5 and PM6:Y6 BHJ films are 5.76 × 10-7 cm2V-1s-1 and 5.02 × 10-5 cm2V-1s-1 from the space-charge-limited current (SCLC) measurements. Through molecular dynamics (MD) simulation, it is observed that halogen bonds can be formed between Y6 dimers, which can provide external channels for electron carrier transfer. Meanwhile, the "A-to-A" type J-aggregates are more likely to be generated between Y6 molecules, and the π-π stacking can be also enhanced, thus increasing the charge transfer rate and electron mobility between Y6 molecules.
Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification of N-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration.
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