The role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in the diagnosis and severity of inflammatory bowel disease in children.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric inflammatory bowel disease (IBD). We analyzed 73 pediatric patients with IBD with a retrospective study design who underwent measurement of fecal calprotectin (FC) and endoscopy and 67 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. We also plotted the ROC diagrams separately for markers to obtain the optimal point and a suitable cutoff point. We enrolled 73 pediatric patients less than 18 years of age with IBD, 40 subjects with UC and 33 with CD and 67 healthy subjects as control group with median age of 9.00 ± 4.61 in all subjects. Furthermore, the mean score of PCDAI or PUCAI in the all subjects was 19.26 ± 16.31. In the ROC curve, the optimal cutoff value for NLR and PLR for detecting IBD was 2.04 (sensitivity 82.1%; specificity 82.9%) and 103 (sensitivity 67.9%; specificity 71.4%). Also, the optimal cutoff values for NLR and PLR for differentiating IBD severity (remission vs. active disease) were 2.94 (sensitivity 77.8%; specificity 50.0%) and 157 (sensitivity 88.9%; specificity 54.5%), respectively. CONCLUSION: Our findings indicate the role of easy and non-invasive markers such as NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease. WHAT IS KNOWN: • NLR and PLR are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. WHAT IS NEW: • In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric IBD. • Our findings indicate the role of NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease.

A comprehensive insight into the correlation between ncRNAs and the Wnt/ß-catenin signalling pathway in gastric cancer pathogenesis.

During the past decades, gastric cancer (GC) has emerged as one of the most frequent malignancies with a growing rate of prevalence around the world. Despite considerable advances in therapeutic methods, the prognosis and management of patients with gastric cancer (GC) continue to be poor. As one of the candidate molecular targets in the treatment of many types of cancer, the Wnt/ß-catenin pathway includes a family of proteins that have important functions in adult tissue homeostasis and embryonic development. The aberrant regulation of Wnt/ß-catenin signaling is strongly correlated with the initiation and development of numerous cancers, including GC. Therefore, Wnt/ß-catenin signaling has been identified as one of the main targets for extending therapeutic approaches for GC patients. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, are important components of epigenetic mechanisms in gene regulation. They play vital roles in various molecular and cellular processes and regulate many signaling pathways, such as Wnt/ß-catenin pathways. Insights into these regulatory molecules involved in GC development may lead to the identification of potential targets for overcoming the limitations of current therapeutic approaches. Consequently, this review aimed to provide a comprehensive overview of ncRNAs interactions involved in Wnt/ß-catenin pathway function in GC with diagnostic and therapeutic perspectives. Video Abstract.

A comprehensive review of the role of lncRNAs in gastric cancer (GC) pathogenesis, immune regulation, and their clinical applications.

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. Although numerous studies have been conducted on advanced GC, the molecular mechanisms behind it remain obscure. Long non-coding RNAs (lncRNAs) are a family of RNA transcripts capable of regulating target genes at transcriptional, post-transcriptional, and translational stages. They do this by modifying mRNAs, miRNAs, and proteins. These RNAs are critical regulators of many biological processes, including gene epigenetics, transcription, and post-transcriptional levels. This article highlights recent results on lncRNAs involved in drug resistance, proliferation, migration, angiogenesis, apoptosis, autophagy, and immune response in GC. The potential clinical implications of lncRNAs as biomarkers and therapeutic targets in GC are also discussed.

Stable softening bioelectronics: A paradigm for chronically viable ester-free neural interfaces such as spinal cord stimulation implants.

Polymer toughness is preserved at chronic timepoints in a new class of modulus-changing bioelectronics, which hold promise for commercial chronic implant components such as spinal cord stimulation leads. The underlying ester-free chemical network of the polymer substrate enables device rigidity during implantation, soft, compliant, conforming structures during acute phases in vivo, and gradual stabilization of materials properties chronically, maintaining materials toughness as device stiffness changes. In the past, bioelectronics device designs generally avoided modulus-changing and materials due to the difficulty in demonstrating consistent, predictable performance over time in the body. Here, the acute, and chronic mechanical and chemical properties of a new class of ester-free bioelectronic substrates are described and characterized via accelerated aging at elevated temperatures, with an assessment of their underlying cytotoxicity. Furthermore, spinal cord stimulation leads consisting of photolithographically-defined gold traces and titanium nitride (TiN) electrodes are fabricated on ester-free polymer substrates. Electrochemical properties of the fabricated devices are determined in vitro before implantation in the cervical spinal cord of rat models and subsequent quantification of device stimulation capabilities. Preliminary in vivo evidence demonstrates that this new generation of ester-free, softening bioelectronics holds promise to realize stable, scalable, chronically viable components for bioelectronic medicines of the future.

Environmental Dynamic Mechanical Analysis to Predict the Softening Behavior of Neural Implants.

When using dynamically softening substrates for neural implants, it is important to have a reliable in vitro method to characterize the softening behavior of these materials. In the past, it has not been possible to satisfactorily measure the softening of thin films under conditions mimicking body environment without substantial effort. This publication presents a new and simple method that allows dynamic mechanical analysis (DMA) of polymers in solutions, such as phosphate buffered saline (PBS), at relevant temperatures. The use of environmental DMA allows measurement of the softening effects of polymers due to plasticization in various media and temperatures, which therefore allows a prediction of the materials behavior under in vivo conditions.

Chronic softening spinal cord stimulation arrays.

OBJECTIVE: We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and does not perturb the underlying spinal cord. APPROACH: We created a softening spinal cord stimulation (SCS) array made from shape memory polymer (SMP)-based flexible electronics. We developed a new photolithographic process to pattern high surface area titanium nitride (TiN) electrodes onto gold (Au) interconnects. The thiol-ene acrylate polymers are stiff at room temperature and soften following implantation into the body. Durability was measured by the duration the devices produced effective stimulation and by accelerated aging in vitro. Stability was measured by the threshold to provoke an electromyogram (EMG) muscle response and by measuring impedance using electrochemical impedance spectroscopy (EIS). In addition, spinal cord modulation of motor cortex potentials was measured. The spinal column and implanted arrays were imaged with MRI ex vivo, and histology for astrogliosis and immune reaction was performed. MAIN RESULTS: For durability, the design of the arrays was modified over three generations to create an array that demonstrated activity up to 29 weeks. SCS arrays showed no significant degradation over a simulated 29 week period of accelerated aging. For stability, the threshold for provoking an EMG rose in the first few weeks and then remained stable out to 16 weeks; the impedance showed a similar rise early with stability thereafter. Spinal cord stimulation strongly enhanced motor cortex potentials throughout. Upon explantation, device performance returned to pre-implant levels, indicating that biotic rather than abiotic processes were the cause of changing metrics. MRI and histology showed that softening SCS produced less tissue deformation than Parylene-C arrays. There was no significant astrogliosis or immune reaction to either type of array. SIGNIFICANCE: Softening SCS arrays meet the needs for research-grade devices in rats and could be developed into human devices in the future.

Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root.

Traditionally, people use harvested Ferula gummosa for medicinal purposes. However, no information about its safety and toxicity is available. In the present study, the toxicological profile of sub-chronic oral administration of hydroalcoholic extract of F. gummosa radix is evaluated in rats. The extract was orally administrated at 100 and 600 mg/kg to male rats for 28 days. After 28 days, clinical signs, mortality, body weights, food and water consumption, organ weights, hematology, serum biochemistry, as well as histopathological and neurobehavioral changes were examined. Also, the sedative effect of this extract was evaluated in mice at the doses of 100, 600, and 800 mg/kg. Its cytotoxicity against human stroma-vascular cells and human renal epithelial cells were also evaluated. No lethality or adverse toxic signs were seen during the experimental period. There were no significant changes in body and organ weights, hematology, serum biochemistry, and histopathological examination. The extract decreased the rotarod performance, but did not increase pentobarbital-induced hypnosis. Also, F. gummosa extract significantly decreased cell viability at the concentrations of higher than 400 µg/mL. In conclusion, the sub-chronic toxicity study of F. gummosa hydroalcoholic extract demonstrated the extract to be safe for the tested dosage and route of administration.

Effects of aqueous extract of turnip leaf (Brassica rapa) in alloxan-induced diabetic rats.

OBJECTIVES: Turnip leaf has been used in folk medicine of Iran for the treatment of diabetes. However,so far no scientific study has been done to support its use in traditional medicine. The present study was carried out to evaluate the possible hypoglycemic efficacy of aqueous extract of turnip leaf (AETL) in diabetic rats. MATERIALS AND METHODS: Alloxan-induced diabetic rats were orally treated with AETL at doses of 200 and 400 mg/kg body weight (bw) per day for 28 days. In order to evaluate the anti-diabetic activity, fasting blood glucose concentrations were determined on the 1(st), 14(th) and 29(th) days. Moreover,at the end of the study, plasma concentrations of total cholesterol, triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), aspartate amino transfarase (AST), and alanine amino transferase (ALT) were measured by the use of standard kits and auto-analyzer. RESULTS: Both doses of AETL significantly decreased (p<0.001) blood glucose and ALT levels in diabetic rats after 28 days of administration. AETL at both doses decreased (p<0.05) plasma total cholesterol and LDL-c in diabetic rats, but they significantly decreased (p<0.05) HDL-c and increased triglycerideand AST levels in a-dose dependent manner. CONCLUSION: The results showed that AETL has a dose- dependent decrease in the blood glucose in diabetic rats. However,we should not be unaware of adverse effects of AETL on lipid profiles and liver enzymes activity, especially decrease of HDL and increase of TG and AST.

Epidemiological, clinical, laboratory findings, and outcomes of disseminated tuberculosis in Tehran, Iran.

BACKGROUND: Disseminated tuberculosis (TB) accounts for 1 to 3% of all TB cases. This retrospective study reviews the clinical, radiological, laboratory findings and outcome in patients with disseminated tuberculosis in an endemic area. METHODS: Medical records were reviewed for patients with disseminated TB admitted to two tertiary centers in Tehran, Iran between 1999 and 2006. RESULTS: Fifty patients were found to have disseminated TB. A miliary pattern was documented in the chest x-ray of 34 patients. Hematologic abnormalities including anemia, leukopenia, and thrombocytopenia were frequently observed. Death occurred in nine of the cases. The mortality rate was significantly higher in diabetic patients, injection drug users, and patients with hematologic abnormalities; however, steroid usage and human immunodeficiency virus infection were not significantly associated with a higher mortality rate. Clinical improvement occurred in 41 patients following treatment. CONCLUSION: Disseminated TB could have different manifestations. Hematologic abnormalities are common and are considered poor prognostic signs in these patients.