The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment

Background

Although thyroid eye disease is a common complication of Graves’ disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray.

Methods

An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets.

Results

Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED.

Conclusion

This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.     

Structural insights into catalysis and dimerization enhanced exonuclease activity of RNase?J

RNase J is a conserved ribonuclease that belongs to the β-CASP family of nucleases. It possesses both endo- and exo-ribonuclease activities, which play a key role in pre-rRNA maturation and mRNA decay. Here we report high-resolution crystal structures of Deinococcus radiodurans RNase J complexed with RNA or uridine 5′-monophosphate in the presence of manganese ions. Biochemical and structural studies revealed that RNase J uses zinc ions for two-metal-ion catalysis. One residue conserved among RNase J orthologues (motif B) forms specific electrostatic interactions with the scissile phosphate of the RNA that is critical for the catalysis and product stabilization. The additional manganese ion, which is coordinated by conserved residues at the dimer interface, is critical for RNase J dimerization and exonuclease activity. The structures may also shed light on the mechanism of RNase J exo- and endonucleolytic activity switch.     

Description of Distorhabditis poonchiana n. gen., n. sp. (Nematoda: Rhabditidae) from Jammu and Kashmir,India

Distorhabditis poonchiana n. gen., n. sp. from humus in Jammu and Kashmir, India, is described and illustrated. The new genus is characterized by a small body; slightly setoff labial region; long tubular gymnostom; prominently cuticularized cheilostom; absence of glottoid apparatus; monoprodelphic reproductive system; vulva (V) = 81 to 84; spicules with trifurcated distal ends, simple gubernaculum, peloderan bursa with eight pairs of bursal papillae arranged in 1 + 1 + 1 + 2 + 1 + 2 arrangement.     

Silymarin: an insight to its formulation and analytical prospects

Silymarin, a potential phytochemical compound obtained from the seeds of Silybum marianum plant has been used as a hepatoprotective agent for more than a decade. So far, eight active components of silymarin flavonolignans have been identified, among which silibinin has been proven the most active. However, it had poor oral bioavailability due to extensive phase II metabolism, low permeability across intestinal epithelial cells, low aqueous solubility, and rapid excretion in bile and urine. Therefore it becomes necessary to understand all its formulation and analytical aspects from past to present, including all of its possible future prospects. In modern research scenario, nanotization strategies of drugs has served as a potential approach to enhance solubility, bioavailability and to develop a robust formulation. Several approaches have been utilized previously to enhance the solubility and bioavailability of silymarin to provide it a robust strength against physical, chemical, and environmental degradation. Nanoscale formulations such as nanoemulsion, nanosuspension, liposomes, and solid–lipid nanoparticles can be used to enhance solubility and to target them to desired cells with minimum harm to normal cells. However, many other approaches exist such as dendrimers, ceramic nanoparticles, and carbon nanotubes, which serve as a great vehicle in drug delivery to transport medicament at target sites. Therefore, the purpose of this review was to develop a better understanding of the problems associated with silymarin and approaches to overcome the difficulties to develop a better and stable formulation for food and pharmaceutical applications.     

BRAF gene: From human cancers to developmental syndromes

The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes—Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome.     

Assessment of the role of general,biochemical and family history characteristics in kidney stone formation

Aim

The main objective of the study was to determine the urinary risk factors involved in kidney stone formation.

Method

In this study a total number of 101 patients (64 males and 37 females) between the age group 2 and 70 years were selected. Personal characteristics like age, family history, clinical sign and symptoms, education, monthly income, living style, smoking or tobacco chewing habit, dietary intake and daily amount of drinking water were recorded.

Results

The study showed that the risk of kidney stone formation was high in the median age group (16–25 years) both in male and female population. The most important factors associated with this were lack of drinking clean water, over weight and obesity as well as family history (37.5% and 27.02% in men and women, respectively).

Conclusion

Our study has confirmed that lack of drinking sufficient amount of water, increasing weight and obesity and family history are some major factors contributing to the increased risk of kidney stone formation. Therefore it is very important to live a healthy life, drink clean water and control weight to prevent such diseases.     

Molecular and Morphometric Characteristics of Ceratomyxa hamour n. sp. (Myxosporea: Bivalvulida) Infecting the Gallbladder of the Orange‐spotted Grouper Epinephelus coioides from the Arabian Gulf,Saudi Arabia

Ceratomyxa hamour n. sp. was found to infect the gallbladder of the orange‐spotted grouper, Epinephelus coioides located off the Saudi Arabian coast of the Arabian Gulf. The infection was reported as a free‐floating spore in the bile, and pseudoplasmodia were not observed. Mature spores were crescent‐shaped and measured on average 7 μm in length and 16 μm in thickness. The polar capsule, meanwhile, had length to width measurements of 4 μm and 3 μm on average. A periodical survey was conducted throughout a sampling period between December 2012 and December 2013, with the results showing that the parasite was present throughout the year with a mean prevalence of 32.6%. The objective of this study was to characterize this new species based on its morphological and molecular differences from previously described species. Molecular analysis based on the partial sequence of the SSU rDNA gene, showed the highest similarity (97.8%) to Ceratomyxa buri, reported in the cultured yellow tail Seriola quinqueradiata in Japan. Indeed, C. buri and the new species described here formed an individual cluster with a high degree of bootstrap support. This is the first reported species of genus Ceratomyxa from the Arabian Gulf fishes off Saudi Arabia.