Inflammatory epithelial cytokines after in vitro respiratory syncytial viral infection are associated with reduced lung function.

Respiratory syncytial virus (RSV) infections in early life predispose children with cystic fibrosis (CF) to more severe lung function decline in later life. The mechanisms explaining the associations between RSV and progression of CF lung disease are not clear. In this study, a human bronchial epithelial cell line and primary human nasal epithelial cells (PNECs) from individuals with CF and healthy control donors were infected with RSV. Real-time PCR, plaque assay, cytokine detection, immunofluorescence and Western blot analyses were performed. RSV is replicated to a higher degree in CF epithelial cells as compared to control cells; however, no defects in innate immune pathways were identified in CF cells. Rather, primary p.Phe508del cystic fibrosis transmembrane conductance regulator PNECs produced more cytokines after RSV infection than control cells. Moreover, interleukin-8 and tumour necrosis factor-α production post RSV negatively correlated with lung function (% predicted forced expiratory volume in 1 s) in the individuals who donated the cells. These data suggest that CF epithelium has a dysfunctional response to RSV allowing for enhanced viral replication and an exaggerated inflammatory response that ultimately may predispose to greater airway inflammation and reduced lung function.

Focal choroidal excavation and giant choroidal cavern in an eye with pachychoroid.

Focal choroidal excavation (FCE) is a localized excavation of the choroid, which can be diagnosed by enhanced depth optical coherence tomography (OCT). Choroidal caverns are focal cavitation areas in the choroid which appear hyporeflective on OCT. These are angular or round, empty spaces with posterior tail of hypertransmission. A 47-year-old female presented to us for a routine eye check-up. The best-corrected visual acuity was 20/20 in both the eyes. On fundus examination, a localized pigmented lesion was seen in the right eye inferior to the optic disc, while the fundus of the left eye was normal. Spectral-domain OCT scan through the lesion showed an FCE and a giant cavern with a posterior tail of hypertransmission. The diameter of the cavern was 977 µ ×264 µ, with a subfoveal choroidal thickness (SFCT) of 360 µ. The SFCT of the other eye was 300 µ. Coexistence of FCE and cavern in an eye with thickened choroid is not yet reported in the literature, and their coexistence provides possible insight into the formation of FCE and caverns in the setting of thickened choroid.

Identification of potential biomarkers for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most predominant subtype of lung cancers and is one of the leading causes of cancer related mortality worldwide. Despite the advancements in the field of cancer diagnostics and therapeutics, detection at an early stage using reliable biomarkers is an unmet clinical need for a plethora of cancers, including LUAD, thus attributing to poor prognosis. In view of this, to identify potential biomarkers and therapeutic candidate genes, the expression of all known human genes was screened in the publicly available 'The Cancer Genome Atlas' (TCGA) samples of LUAD patients which resulted in the identification of overexpressed genes. Further analysis of these genes across various patient sample datasets revealed that ZNF687, ODR4, PBXIP1, PYGO2, METTL3, PIGM and RAD1 are consistently more highly expressed in LUAD. Higher expression of these genes either alone or in combination is correlated with poor survival of LUAD patients. Hence, in this study we propose that these identified genes could serve as potential candidates as gene signatures or biomarkers for LUAD that require further investigation in large cohorts of LUAD samples.

Lateralized Expression of Cortical Perineuronal Nets during Maternal Experience is Dependent on MECP2.

Cortical neuronal circuits along the sensorimotor pathways are shaped by experience during critical periods of heightened plasticity in early postnatal development. After closure of critical periods, measured histologically by the formation and maintenance of extracellular matrix structures called perineuronal nets (PNNs), the adult mouse brain exhibits restricted plasticity and maturity. Mature PNNs are typically considered to be stable structures that restrict synaptic plasticity on cortical parvalbumin+ (PV+) GABAergic neurons. Changes in environment (i.e., novel behavioral training) or social contexts (i.e., motherhood) are known to elicit synaptic plasticity in relevant neural circuitry. However, little is known about concomitant changes in the PNNs surrounding the cortical PV+ GABAergic neurons. Here, we show novel changes in PNN density in the primary somatosensory cortex (SS1) of adult female mice after maternal experience [called surrogate (Sur)], using systematic microscopy analysis of a whole brain region. On average, PNNs were increased in the right barrel field and decreased in the left forelimb regions. Individual mice had left hemisphere dominance in PNN density. Using adult female mice deficient in methyl-CpG-binding protein 2 (MECP2), an epigenetic regulator involved in regulating experience-dependent plasticity, we found that MECP2 is critical for this precise and dynamic expression of PNN. Adult naive Mecp2-heterozygous (Het) females had increased PNN density in specific subregions in both hemispheres before maternal experience, compared with wild-type (WT) littermate controls. The laterality in PNN expression seen in naive Het (NH) was lost after maternal experience in Sur Het (SH) mice, suggesting possible intact mechanisms for plasticity. Together, our results identify subregion and hemisphere-specific alterations in PNN expression in adult females, suggesting extracellular matrix plasticity as a possible neurobiological mechanism for adult behaviors in rodents.

Anticancer potential of curcumin: preclinical and clinical studies.

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.