RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

Thrombin activatable fibrinolysis inhibitor and thrombin-antithrombin-III-complex levels in patients with gastric cancer

The relation between cancer and coagulation is the subject of investigation since a relation between tumor and thrombosis has been determined. Antithrombin III is an important thrombin inhibitor, and increased thrombin?Cantithrombin (TAT) complex levels activate coagulation. Activated thrombin activatable fibrinolysis inhibitor (TAFI) inhibits the conversion of plasminogen to plasmin. In addition, it directly inactivates plasmin. Defective fibrinolysis increases the risk of thrombosis. In this study, we evaluated homeostatic parameters, TAFI, and TAT levels in patients with gastric cancer applying to the medical oncology outpatient clinic. Fifty-two patients and 35 healthy controls were included. ELISA was used to measure TAFI and TAT complex levels. These were statistically higher in the patient group (p?<?0.05 and p?=?0.001, respectively). D-dimer levels were higher in stage IV (p?=?0.05). Correlations between lymph nodes and TAFI and TAT levels were examined. Weak but positive correlation between lymph nodes and TAFI was detected (R?=?0.452, p?=?0.027). TAFI and TAT levels were evaluated using relative operating characteristic analysis to differentiate the disease. TAT was more specific than TAFI according to this analysis (TAFI area under curve (AUC), 0.676; TAT AUC, 0.874). Thrombotic events and bleeding disorders need to be borne in mind in gastric cancer. This situation is due to the impairment of the balance between coagulation and fibrinolysis. Further studies are now needed to evaluate the effects of TAFI and TAT on survey and prognosis as well as the potential of these parameters as tumor markers for gastric cancer.     

Mediastinal Seroma Post Laparoscopic Repair of Type IV Paraesophageal Hernia

Laparoscopic repair of paraesophageal hernia is safe and feasible and can provide comparable results for patients with type IV paraesophageal hernia. We report a rare case of mediastinal seroma in an 80-year-old gentleman who had a giant type IV paraesophageal hernia and was eventually admitted to our hospital for elective laparoscopic repair and recovered very well after surgery with resolution of the atelectatic lungs and air-fluid collection in his chest.     

Effects of supplemental thyme extract (Thymus vulgaris L.) on growth performance,intestinal microbial populations,and meat quality in Japanese quails

The aim of the current study was to investigate the effects of dietary supplementation with thyme extract as growth promoter agent on growth performance, intestinal microbial populations, and thigh meat quality of Japanese quail. A total of one hundred eighty 1-day-old Japanese quails were randomly allocated to three treatments with four replicates per treatment and 15 quail chicks per pen. The dietary treatments consisted of basal control diet (CO) without any added compounds, virginiamycin (VM, 200 mg/kg), and thyme extract (TH, 100 mg/kg). Daily feed intake for each pen was recorded. The average body weight gain (BWG) and feed intake (FI) adjusted for mortality to 21 and 35 days of age were used to calculate the feed conversion ratio (FCR). At day 35, two birds per replicate were slaughtered for determination of intestinal weights and also for thigh meat quality. Supplementing VM significantly decreased the FCR of quails at day 35. The results showed that the count of lactobacillus bacteria increased in birds fed the TH diet compared to VM and CO treatments. Also, supplemental TH decreased the number of coliforms in the ileum compared to the CO diet. Japanese quails fed the TH diet had significantly lower 2-thiobarbituric acid-reactive substances (TBARS) than the VM and CO treatments. Water holding capacity (WHC) was significantly increased in quails fed the TH diet. In conclusion, TH can increase the number of beneficial bacteria (lactobacillus bacteria) and decrease harmful ones (coliforms). Also, TH has good effects on thigh meat quality as indicated by the decrease in TBARS and the increase in WHC, but it has not affected the growth performance.     

Identification and Characterization of the Insecticidal Toxin “Makes Caterpillars Floppy” in Photorhabdus temperata M1021 Using a Cosmid Library

Photorhabdus temperata is an entomopathogenic enterobacterium; it is a nematode symbiont that possesses pathogenicity islands involved in insect virulence. Herein, we constructed a P. temperata M1021 cosmid library in Escherichia coli XL1-Blue MRF` and obtained 7.14 × 10⁵ clones. However, only 1020 physiologically active clones were screened for insect virulence factors by injection of each E. coli cosmid clone into Galleria mellonella and Tenebrio molitor larvae. A single cosmid clone, PtC1015, was consequently selected due to its characteristic virulent properties, e.g., loss of body turgor followed by death of larvae when the clone was injected into the hemocoel. The sequence alignment against the available sequences in Swiss-Prot and NCBI databases, confirmed the presence of the mcf gene homolog in the genome of P. temperata M1021 showing 85% homology and 98% query coverage with the P. luminescens counterpart. Furthermore, a 2932 amino acid long Mcf protein revealed limited similarity with three protein domains. The N-terminus of the Mcf encompassed consensus sequence for a BH3 domain, the central region revealed similarity to toxin B, and the C-terminus of Mcf revealed similarity to the bacterial export domain of ApxIVA, an RTX-like toxin. In short, the Mcf toxin is likely to play a role in the elimination of insect pests, making it a promising model for use in the agricultural field.