Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.

Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes. Snail-expressing cells secrete the matricellular protein Mindin, which functions in an autocrine fashion to activate a Src-STAT3 pathway to reinforce their stem/progenitor phenotype. This pathway is activated by the engagement of Mindin with the leukocyte-specific integrin, CD11b (ITGAM), which is also unexpectedly expressed by epidermal keratinocytes. Interestingly, disruption of this signaling module in human cSCC attenuates tumorigenesis, suggesting that targeting Mindin would be a promising therapeutic approach to hinder cancer recurrence.

Cognition, autonomic function, and intellectual outcomes of the paramedical health-care personnel in the hospital settings.

BACKGROUND: In the dedicated intensive care settings, health-care providers need to have higher temporal cognition and sympathovagal balance to optimally deliver critical care interventions. OBJECTIVE: The objective of the study was to estimate the parameters of the temporal cognition and autonomic function of paramedical staffs in acute health-care settings. MATERIALS AND METHODS: In this study on 81 healthy adult paramedical personnel, temporal cognition was assessed using auditory reaction time (ART), visual reaction time (VRT), critical flicker fusion frequency (CFFF), Stroop test (ST), and digits forward test (DFT); Autonomic functions were assessed by heart rate (HR) and blood pressure (BP) variability, and all these outcomes were analyzed with their academic performance. RESULTS: Out of 81 healthy adult nonteaching technical personnel, majority was female; the mean age was 25.10 ± 3.93 years. Age and gender were not significantly related with screen times in terms of smartphone use, playing video games, or regularly using computer; academic performances were also not significantly related with screen times in terms of smartphone use, playing video games, or regularly using computer. In the conventional domains, during analysis of physiological and psychological variables under study, there was no significant relation with screen times when compared with HR, systolic BP, diastolic BP, mean arterial pressure, body mass index, ART, VRT, CFFF, ST, and DFT. Playing video games and regular computer use were significantly correlated with age, gender, AP, CFFF, ST, and DFT. CONCLUSION: This study on paramedical personnel showed a positive relation of temporal cognition and sympathovagal autonomic balance with performing a task or function.

Notch signalling in cervical cancer.

The initial discovery of key developmental signalling pathways, largely using classical genetic approaches in model organisms, was followed by an intense burst of characterisation of the molecular components. Studies also began demonstrating a role for these pathways in oncogenesis. Patterns of mutations in Notch pathway components, such as those reported in subsets of hematological malignancies, have been easier to study, and the cumulative information is leading to potentially new therapies. However, it has been more challenging to clearly define the role of the Notch pathway in human solid tumours, given the absence of widespread specific activating or repressive mutations in key components of the pathway. In this review, we trace more than two decades of work looking at the role of Notch signalling in human cervical cancer progression. We document the contrasting reports on a tumour suppressive role and pro-oncogenic role in cervical cancers. However, an analysis of recent genomic data strikingly shows both widespread features of Notch expression and genetic changes that largely amplify positive regulators and delete negative controllers of the Notch pathway. This analysis reinforces a largely pro-oncogenic role for Notch signalling and lays the foundation for a nuanced exploration of synergistic and targeted therapies. Lastly, we further trace some of the complex challenges in advanced cervical cancer progression, including issues of cancer stem cells and metastasis.

MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia.

The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients. Earlier, miRNA182-5p upregulation was reported in several solid tumours and haematological malignancies. We undertook a strategy involving transient modulation and CRISPR/Cas9 (clustered regularly interspersed short palindromic repeats)-mediated knockout of the MIR182 locus in CML cells. The lineage contribution was assessed by methylcellulose colony formation assay. The transient modulation of miRNA182-5p revealed a biased phenotype. Strikingly, Δ182 cells (homozygous deletion of MIR182 locus) produced a marked shift in lineage distribution. The phenotype was rescued by ectopic expression of miRNA182-5p in Δ182 cells. A bioinformatic analysis and Hes1 modulation data suggested that Hes1 could be a putative target of miRNA182-5p. A reciprocal relationship between miRNA182-5p and Hes1 was seen in the context of TK inhibition. In conclusion, we reveal a key role for miRNA182-5p in restricting the myeloid development of leukemic cells. We propose that the Δ182 cell line will be valuable in designing experiments for next-generation pharmacological interventions.

A statistical quantification of radiobiological metrics in Intensity Modulated Radiation Therapy evaluation.

UNLABELLED: The dosimetric parameters from the DVH cannot predict the amount of tumor kill and normal tissue complications directly but it can assess the conformity and homogeneity of the physical dose distributions. For example, the D-V parameter V20 (Percentage of lung volume receiving 20Gy) is used to gauge the incidence of grade =2 or grade =3 radiation pneumonitis with the plan. But the complication can be correlated to more than one point in the DVH (eg. V5, V40, D50) and it is treatment technique dependent. The aim of this study is to quantify the uncertainty of physical dose metrics to predict the clinical outcomes of the radiotherapy treatments. METHODS: The radiobiological estimates such as TCP and NTCP were made for a cohort of 50 patients (15-Brain; 20-H and N; 15-Pelvis) using the D-V parameters. A statistical analysis based on Spearman ranking coefficient correlation was performed to determine the correlation of the physical plan quality indicators with that of radiobiological estimates. RESULTS: The correlation between the Conformity Index and the Tumor Control probability was found to be good and the dosimetric parameters for optic nerves, optic chiasm, brain stem, normal brain and parotids correlated well with the Normal Tissue Complication Probability estimates compared to other normal structures. A follow up study (median duration: 28 Months) was also performed. There was no grade 3 or grade 4 normal tissue complications observed. Local tumor control was found to be higher in brain (90%) and pelvic cases (95%) whereas a decline of 75% was noted with Head and Neck cases. CONCLUSIONS: The EUD concept of radiobiological model used in the software determines the TCP and NTCP values which can predict precise outcomes with the use of dose volume data in the voxel level. The uncertainty of using physical dose metrics for plan evaluation is quantified with the statistical analysis. It is also helpful in ranking rival treatment plans.

Giant middle fossa epidermoid presenting as holmes' tremor syndrome.

Intracranial dermoids may gradually reach an enormous size before the onset of symptoms. Common clinical presentations of intracranial epidermoid include headache and seizures. We present a case of a 35-year female patient with giant middle fossa epidermoid that presented with Holmes' tremor syndrome, and we review the relevant literature. To the best of our knowledge, such a presentation has not previously been described in the literature.

Cholinesterase inhibitors from botanicals.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh), appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com) are also presented and the scope for future research is discussed.

Frequency and distribution of Epstein-Barr virus infection and its association with P53 expression in a series of primary nodal non-Hodgkin lymphoma patients from South India.

This study investigated the prevalence of Epstein-Barr virus (EBV) infection and its association with P53 expression in a panel of 87 previously untreated nodal non-Hodgkin lymphomas (NHLs) from India. Polymerase chain reaction specific for Epstein Barr nuclear antigen 1 (EBNA1) and EBNA-3C was performed on the lymphnode tissue DNA, while P53 expression was analyzed by immunohistochemistry. EBV, predominantly type A strain, was detected in 27/87 (31%) nodal lymphoid malignancies, 11/46 diffuse large B-cell lymphomas, 6/17 follicular lymphoma, 4/6 anaplastic large cell lymphomas (ALCL), 5/11 peripheral T-cell lymphomas (PTCL) and 1/7 lymphoblastic lymphomas. EBV infection was more frequently observed in a specific subset of nodal NHL, suggesting a causative role of EBV infection in the pathogenesis of ALCL and PTCL. There was no significant association between EBV and P53 expression in our series of NHL patients.