NK cells: An attractive candidate for cancer therapy

Natural killer (NK) cells have significant capability in tumor immune-surveillance. The ability of lyse transformed cells immediately in an antigen-independent manner make them an attractive candidate for cancer cell therapy. Despite employment of NK cells in cancer immunotherapy, clinical trials are faced with serious limitations such as trouble with the penetration of NK cells in tumor sites, limited in vivo persistence, and tumor microenvironment interference. Taken together, the NK-cell cancer therapy is still infant scenario that has a long way to be translated in clinic. Current article first reviews characteristic features of NK lymphocytes. Then, it discusses about important disruptive barriers and motivator in the developmental stages of NK cells like as tumor microenvironment. Finally, some revolutionary approaches are highlighted utilizing of NK cells in cancer therapy.     

Response of biomass,hydrology and biogeochemistry to alternative approaches of cutting a northern forest: model comparisons

Biogeochemistry - The biogeochemical model, PnET-BGC, was modified and parameterized using field data from an experimental whole-tree harvest of watershed (W5) in 1983–1984 at the Hubbard...     

A new approach in wetland systems for domestic wastewater treatment using Phragmites sp.

The conventional wetland system using Phragmites sp. is in existence since 20 years. The constructed wetland system has not gained much popularity due to large land area requirement, clogging of beds and need for capital investment. The aim of the study is to develop a new approach to the horizontal flow wetlands system (termed bio-rack) for treatment of domestic wastewater. The new system dealt with an engineered attached growth matrix and a high microbial degradation rate. The study on bio-rack was undertaken in a horizontal flow pilot plant using Phragmites sp. and experiments were carried out for various parameters. Analytical data were collected during the studies which include temperature, pH, chemical oxygen demand (COD), biological oxygen demand (BOD₅), dissolved oxygen (DO), chlorides, total dissolved solids (TDS), total suspended solids (TSS), ammonia nitrogen (NH₃-N), phosphate (PO₄-P) and most probable number (MPN). This paper also studies microbial flora present in the system by isolating and identifying the microorganisms, and also measuring total viable count (TVC). Morphological aspects with reference to the growth of plant were studied and it indicated high plant yield. At optimum hydraulic retention time (HRT) of 10 h, approximately 75.15% COD, 86.59% BOD₅, 27.54% TDS, 73.13% TSS, 8.86% Chlorides, 70.22% NH₃-N, 31.71% PO₄-P and 92.11% MPN reduction was achieved in bio-rack system. A comparative evaluation was done with the conventional wetland system and better treatment efficiency was observed in the bio-rack system. This result indicates a possibility of development of a substantially effective system compared to any other methods on constructed wetland.     

Heart rate variability and spontaneous baroreflex sequences in supine healthy volunteers subjected to nasal positive airway pressure.

To determine the dynamic effects of short-term nasal positive airway pressure (nPAP) on cardiovascular autonomic control, continuous recordings of noninvasively obtained hemodynamic measurements and heart rate variability (HRV) were obtained in 10 healthy subjects during frequency-controlled breathing (between 0.20 and 0.24 Hz) in supine posture under different pressures of nPAP ranging from 3 to 20 cmH(2)O. HRV was assessed using spectral analysis of the R-R interval. The slope of the regression line between spontaneous systolic blood pressure and pulse interval changes was taken as an index of the sensitivity of arterial baroreflex modulation of heart rate (sequence method). Application of nPAP resulted in a pressure-dependent decrease of cardiac output and stroke volume (P < 0.05, ANOVA) and in an increase in total peripheral resistance (P < 0.03, ANOVA). Hemodynamic changes under increasing nPAP were accompanied by a decrease in total power of HRV despite mean R-R interval remaining unchanged. The overall decrease in HRV was accompanied by a reduction across all frequency bands when absolute units were used (P < 0.01). When the power of low frequency and high frequency was calculated in normalized units, a diminished high frequency and an increased low-to-high frequency ratio were observed (P < 0.05). Compared with low levels of nPAP, pressure levels of >10 cmH(2)O were associated with a significant decline in the mean slope of spontaneous baroreceptor sequences (P < 0.04). These findings indicate that short-term administration of nPAP in normal subjects exerts significant alterations in R-R interval variability and spontaneous baroreflex modulation of heart rate.     

LAMTOR5 expression level is a biomarker for colorectal cancer and lncRNA LAMTOR5-AS1 predicting miRNA sponging effect

Molecular Biology Reports - Strong evidence indicated that high expression of HBXIP (also known as LAMTOR5) promotes cancer cells proliferation and helps cancer progression. Long non-coding RNAs...     

Polymorphic core promoter GA-repeats alter gene expression of the early embryonic developmental genes

Protein complexes that bind to ‘GAGA’ DNA elements are necessary to replace nucleosomes to create a local chromatin environment that facilitates a variety of site-specific regulatory responses. Three to four elements are required for the disruption of a preassembled nucleosome. We have previously identified human protein-coding gene core promoters that are composed of exceptionally long GA-repeats. The functional implication of those GA-repeats is beginning to emerge in the core promoter of the human SOX5 gene, which is involved in multiple developmental processes. In the current study, we analyze the functional implication of GA-repeats in the core promoter of two additional genes, MECOM and GABRA3, whose expression is largely limited to embryogenesis. We report a significant difference in gene expression as a result of different alleles across those core promoters in the HEK-293 cell line. Across-species homology check for the GABRA3 GA-repeats revealed that those repeats are evolutionary conserved in mouse and primates (p < 1 × 10^− 8). The MECOM core promoter GA-repeats are also conserved in numerous species, of which human has the longest repeat and complexity. We propose a novel role for GA-repeat core promoters to regulate gene expression in the genes involved in development and evolution.     

Circular RNA-associated ceRNA network involved in HIF-1 signalling in triple-negative breast cancer: circ_0047303 as a potential key regulator

The aggressive and highly metastatic nature of triple-negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF-1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non-coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA-associated ceRNA network involved in HIF-1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303-mediated ceRNA regulatory axes have been extracted and validated across TNBC samples. We show that circ_0047303 has the highest degree in the circRNA-associated ceRNA network and shows a significant up-expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis-related genes, including HIF-1, EIF4E2 and VEGFA in TNBC through sponging the tumour-suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC.     

High level expression,purification and immunogenicity analysis of a protective recombinant protein against botulinum neurotoxin type E

Botulinum neurotoxin type E heavy chain consists of two domains: N-terminal half as a translocation domain and C-terminal half (Hcc) as a binding domain. In this research a synthetic gene fragment encoding the binding domain of botulinum neurotoxin type E (BoNT/E-Hcc) was highly expressed in Escherichia coli by pGEX4T-1 vector. After purification, the recombinant BoNT/E-Hcc was evaluated by SDS-PAGE and western blot (immunoblot) analysis. Average yields obtained in this research were 3.7 mg recombinant BoNT/E-Hcc per liter of bacterial culture. The recombinant protein was injected in mice for study of its protection ability against botulinum neurotoxin type E challenges. The challenge studies showed that, vaccinated mice were fully protected against 10⁴ × minimum lethal dose of botulinum neurotoxin type E.