Correction to: The protean world of non-coding RNAs in glioblastoma

Journal of Molecular Medicine -     

Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Total Hip Arthroplasty in Ankylosing Spondylitis With Extension Contracture of Hips

Background

Despite significant pain relief following total hip arthroplasty (THA) in patients with ankylosing spondylitis, a small subset of patients presenting with extra-articular extension contracture of hips remains unsatisfied.

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches

Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre-metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O₂, exosomes secreted under normoxic condition [Exo^Normoxic]) and hypoxic (1% O₂, exosomes secreted under hypoxic condition [Exo^Hypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that Exo^Hypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that Exo^Hypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in Exo^Normoxic and Exo^Hypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.     

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).     

New therapeutics based on emerging concepts in pulmonary fibrosis

Introduction: Fibrosis is an irreversible pathological endpoint in many chronic diseases, including pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal condition characterized by (myo)fibroblast proliferation and transformation in the lung, expansion of the extracellular matrix, and extensive remodeling of the lung parenchyma. Recent evidence indicates that IPF prevalence and mortality rates are growing in the United States and elsewhere. Despite decades of research on the pathogenic mechanisms of pulmonary fibrosis, few therapeutics have succeeded in the clinic, and they have failed to improve IPF patient survival.

Areas covered: Based on a literature search and our own results, we discuss the key cellular and molecular responses that contribute to (myo)fibroblast actions and pulmonary fibrosis pathogenesis; this includes signaling pathways in various cells that aberrantly and persistently activate (myo)fibroblasts in fibrotic lesions and promote scar tissue formation in the lung.

Expert opinion: Lessons learned from recent failures and successes with new therapeutics point toward approaches that can target multiple pro-fibrotic processes in IPF. Advances in preclinical modeling and single-cell genomics will also accelerate novel discoveries for effective treatment of IPF.     

Treatment options for unstable trochanteric fractures: Screw or helical proximal femoral nail

Purpose: To compare treatment outcome of screw proximal femoral nail (PFN) system with that of a helical PFN. Methods: The study included 77 patients with closed unstable intertrochanteric fracture classified as AO 31A2 & 31A3, between June 2008 to August 2011. Inclusion criteria were: all mature skeletons above 50 years of age; closed unstable trochanteric fracture classified as AO 31A2 & A3. Exclusion criteria were: immature skeleton, pathological fracture of any cause other than osteoporosis, inability to walk independently prior to injury. Patients were randomized to 2 treatment groups based on admission sequence. Forty patients were treated with screw PFN and thirty seven were treated with helical PFN. Results: Both groups were similar in respect of time of surgery, blood loss and functional assessment and duration of hospitalization. In screw PFN group 2 patients had superficial wound infection, 1 patient had persistent hip pain and 1 patient had shortening >1 cm but <2 cm, while in helical PFN group 1 patient had superficial wound infection. Conclusion: Both screw and helical PFN are very effective implants in osteoporotic and unstable trochanteric fractures even in Indian patients where the bones are narrow and neck diameter is small. It is an implant of choice for osteoporotic and unstable trochanteric fractures.