Efficacy and safety of nanohybrids comprising silver nanoparticles and silicate clay for controlling Salmonella infection

Developing effective and safe drugs is imperative for replacing antibiotics and controlling multidrug-resistant microbes. Nanoscale silicate platelet (NSP) and its nanohybrid, silver nanoparticle/NSP (AgNP/NSP), have been developed, and the nanohybrids show a strong and general antibacterial activity in vitro. Here, their efficacy for protecting Salmonella-infected chicks from fatality and septicemia was evaluated. Both orally administrated NSP and AgNP/NSP, but not AgNPs alone, effectively reduced the systemic Salmonella infection and mortality. In addition, quantitative Ag analyses demonstrated that Ag deposition from AgNP/NSP in the intestines was less than that from conventional AgNPs, indicating that the presence of NSP for immobilizing AgNPs reduced Ag accumulation in tissue and improved the safety of AgNPs. These in vivo results illustrated that both NSP and AgNP/NSP nanohybrid represent potential agents for controlling enteric bacterial infections

Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling

BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways

The investigation of Mitogen-Activated Protein kinase Phosphatase-1 as a potential pharmacological target in non-small cell lung carcinomas, assisted by non-invasive molecular imaging

<p>Abstract</p> <p>Background</p> <p>Invasiveness and metastasis are the most common characteristics of non small cell lung cancer (NSCLC) and causes of tumour-related morbidity and mortality. Mitogen-activated protein kinases (MAPKs) signalling pathways have been shown to play critical roles in tumorigenesis. However, the precise pathological role(s) of mitogen-activated protein kinase phosphatase-1 (MKP-1) in different cancers has been controversial such that the up-regulation of MKP-1 in different cancers does not always correlate to a better prognosis. In this study, we showed that the induction of MKP-1 lead to a significant retardation of proliferation and metastasis in NSCLC cells. We also established that rosiglitazone (a PPARγ agonist) elevated MKP-1 expression level in NSCLC cells and inhibited tumour metastasis.</p> <p/> <p>Methods</p> <p>Both wildtype and dominant negative forms of MKP-1 were constitutively expressed in NSCLC cell line H441GL. The migration and invasion abilities of these cells were examined in vitro. MKP-1 modulating agents such as rosiglitazone and triptolide were used to demonstrate MKP-1's role in tumorigenesis. Bioluminescent imaging was utilized to study tumorigenesis of MKP-1 over-expressing H441GL cells and anti-metastatic effect of rosiglitazone.</p> <p>Results</p> <p>Over-expression of MKP-1 reduced NSCLC cell proliferation rate as well as cell invasive and migratory abilities, evident by the reduced expression levels of MMP-2 and CXCR4. Mice inoculated with MKP-1 over-expressing H441 cells did not develop NSCLC while their control wildtype H441 inoculated littermates developed NSCLC and bone metastasis. Pharmacologically, rosiglitazone, a peroxisome proliferator activated receptor-γ (PPARγ) agonist appeared to induce MKP-1 expression while reduce MMP-2 and CXCR4 expression. H441GL-inoculated mice receiving daily oral rosiglitazone treatment demonstrated a significant inhibition of bone metastasis when compared to mice receiving sham treatment. We found that rosiglitazone treatment impeded the ability of cell migration and invasion <it>in vitro</it>. Cells pre-treated with triptolide (a MKP-1 inhibitor), reversed rosiglitazone-mediated cell invasion and migration.</p> <p>Conclusion</p> <p>The induction of MKP-1 could significantly suppress the proliferative and metastatic abilities of NSCLC both in vitro and in vivo. Therefore, MKP-1 could be considered as a potential therapeutic target in NSCLC therapy and PPARγ agonists could be explored for combined chemotherapy.</p

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Imaging Findings in Mucin-producing Carcinoma of the Gallbladder

Mucin-producing carcinoma of the gallbladder is rare, and its imaging features have not been well documented. Its symptoms and signs are nonspecific and the prognosis of the disease is poor. We present a 73-year-old male with mucin-producing carcinoma of the gallbladder, emphasizing its imaging features on ultrasound, computed tomography and magnetic resonance imaging. The tumor usually presents as a cauliflower-like soft tissue mass with small calcified spots in the gallbladder wall and some laminated high viscosity fluid inside the gallbladder cavity. Recognition of these features can provide clues to the diagnosis of mucin-producing carcinoma of the gallbladder

New Multidrug-Resistant Salmonella enterica Serovar Anatum Clone, Taiwan, 2015–2017

In 2011, a Salmonella enterica serovar Anatum clone emerged in Taiwan. During 2016–2017, infections increased dramatically, strongly associated with emergence and spread of multidrug-resistant strains with a plasmid carrying 11 resistance genes, including blaDHA-1. Because these resistant strains infect humans and food animals, control measures are urgently needed

Epigenetic Roles of MLL Oncoproteins Are Dependent on NF-κB

SummaryMLL fusion proteins in leukemia induce aberrant transcriptional elongation and associated chromatin perturbations; however, the upstream signaling pathways and activators that recruit or retain MLL oncoproteins at initiated promoters are unknown. Through functional and comparative genomic studies, we identified an essential role for NF-κB signaling in MLL leukemia. Suppression of NF-κB led to robust antileukemia effects that phenocopied loss of functional MLL oncoprotein or associated epigenetic cofactors. The NF-κB subunit RELA occupies promoter regions of crucial MLL target genes and sustains the MLL-dependent leukemia stem cell program. IKK/NF-κB signaling is required for wild-type and fusion MLL protein retention and maintenance of associated histone modifications, providing a molecular rationale for enhanced efficacy in therapeutic targeting of this pathway in MLL leukemias

Predicting Long-Term Care Service Demands for Cancer Patients: A Machine Learning Approach

Background: Long-term care (LTC) service demands among cancer patients are significantly understudied, leading to gaps in healthcare resource allocation and policymaking. Objective: This study aimed to predict LTC service demands for cancer patients and identify the crucial factors. Methods: 3333 cases of cancers were included. We further developed two specialized prediction models: a Unified Prediction Model (UPM) and a Category-Specific Prediction Model (CSPM). The UPM offered generalized forecasts by treating all services as identical, while the CSPM built individual predictive models for each specific service type. Sensitivity analysis was also conducted to find optimal usage cutoff points for determining the usage and non-usage cases. Results: Service usage differences in lung, liver, brain, and pancreatic cancers were significant. For the UPM, the top 20 performance model cutoff points were adopted, such as through Logistic Regression (LR), Quadratic Discriminant Analysis (QDA), and XGBoost (XGB), achieving an AUROC range of 0.707 to 0.728. The CSPM demonstrated performance with an AUROC ranging from 0.777 to 0.837 for the top five most frequently used services. The most critical predictive factors were the types of cancer, patients’ age and female caregivers, and specific health needs. Conclusion: The results of our study provide valuable information for healthcare decisions, resource allocation optimization, and personalized long-term care usage for cancer patients