Functional Significance of Mirna-149 in Lung Cancer: Can it be Utilized as a Potential Biomarker or a Therapeutic Target?

Accumulating evidence has documented the significance of miR-149 as a promising tumor-suppressive non-coding RNA that play critical roles in regulating genes involved in cancer growth and metastasis. Notably, the ability of miR-149 to be utilized as a potential biomarker in the diagnosis/prognosis or a therapeutic target has also been explored using various cellular and preclinical models, as well as in clinical settings of lung cancer. While the applicability of miR-149 in assessing tumor progression has been suggested, its potential in predicting treatment outcomes is needed to be verified in diverse settings of lung cancer patients. The current review presents an overview of the functional significance of miR-149 with ongoing challenges in non-small cell lung cancer.

Rapid Magnetic 3D Printing of Cellular Structures with MCF-7 Cell Inks.

A contactless label-free method using a diamagnetophoretic ink to rapidly print three-dimensional (3D) scaffold-free multicellular structures is described. The inks consist of MCF-7 cells that are suspended in a culture medium to which a paramagnetic salt, diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen salt hydrate (Gd-DTPA), is added. When a magnetic field is applied, the host fluid containing the paramagnetic salt is attracted towards regions of high magnetic field gradient, displacing the ink towards regions with a low gradient. Using this method, 3D structures are printed on ultra-low attachment (ULA) surfaces. On a tissue culture treated (TCT) surface, a 3D printed spheroid coexists with a two-dimensional (2D) cell monolayer, where the composite is termed as a 2.5D structure. The 3D structures can be magnetically printed within 6 hours in a medium containing 25 mM Gd-DTPA. The influence of the paramagnetic salt on MCF-7 cell viability, cell morphology, and ability of cells to adhere to each other to stabilize the printed structures on both ULA and TCT surfaces is investigated. Gene expressions of hypoxia-inducible factor 1-alpha (HIF1α) and vascular endothelial growth factor (VEGF) allow comparison of the relative stresses for the printed 3D and 2.5D cell geometries with those for 3D spheroids formed without magnetic assistance. This magnetic printing method can be potentially scaled to a higher throughput to rapidly print cells into 3D heterogeneous cell structures with variable geometries with repeatable dimensions for applications such as tissue engineering and tumour formation for drug discovery.

Evidence of Faradaic Reactions in Electrostatic Atomizers.

Any rational theory of electrostatic atomizers (EAs) would require a detailed understanding of the nature of the polarized layer near the electrode, since this is the source of the electric charge carried by the jets issued from the EAs. The polarized layer either is driven out as the electrically-driven Smoluchowski flow and/or entrained by the viscous shear imposed by the bulk flow. The standard Gouy-Chapman theory of polarized diffuse layers implies zero electric current passing across the layer, which is impossible to reconcile with the fact that there are leak currents in the EAs. Here, we show that the electric current through the EA is controlled by faradaic reactions at the electrodes. The experiments were conducted with stainless steel or brass pin-like cathodes and three different anode (the conical nozzle) materials, which were copper, stainless steel, and brass. The different electrode materials resulted in different spray, leakage, and total currents in all the cases. Accordingly, it is shown that the total electric current generated by EAs can be controlled by the cathode and anode materials, i.e., by faradaic reactions on them. This lays the foundation for a more detailed understanding and description of the operation of EAs.

ANTIOXIDANTS EFFECTS IN CANCER SURVIVORS: A SHORT PERSPECTIVE.

There have been intense debates on the use of antioxidants as neoadjuvant therapy or in combination with anti-cancer agents in the treatment of human malignancies. While the safety and effectiveness of commonly used dietary antioxidants have been thoroughly assessed during chemotherapy and radiation therapy in cancer patients, more detailed analysis of their effects are needed to define its potential use in cancer survivors. Here, we summarize the findings of few comprehensive studies that investigated the potential implications of antioxidants in cancer survivors.

Low prevalence of latent autoimmune diabetes in adults in northern India.

AIM: To study the frequency of islet antibodies in a large cohort of clinic- and community-based patients with Type 2 diabetes in northern India. METHODS: We measured glutamic acid decarboxylase (GAD) antibodies in 618 adults with Type 2 diabetes (378 patients with diabetes attending a hospital clinic, 240 patients diagnosed in a community survey) and in 192 healthy subjects residing in north India. Islet antigen 2 (IA2) antibodies were also studied in a proportion of the patients with diabetes (n = 492) and in a control population (n = 191). GAD and IA2 antibodies were measured by immunoprecipitation of the respective (35) S-labelled recombinant antigen. RESULTS: We found that GAD antibodies were present in nine (1.5%) patients with diabetes (clinic population: 0.8%, community study: 2.5%), a prevalence similar to that among the subjects without diabetes (n = 2; 1%). IA2 antibodies were detected in seven patients with Type 2 diabetes (1.4%) and in two healthy control subjects (1.0%). The frequency of either GAD or IA2 antibodies was similar in people with and without diabetes (3.2 vs 2.1%). No subject was found to have both antibodies. Insulin requirement was higher among antibody-positive than among antibody-negative patients (GAD antibody: 33 vs 6.3%; P = 0.001; GAD or IA2 antibody: 23.1 vs 6.4%; P = 0.02); however, other clinical features were similar in the two groups. CONCLUSIONS: In the present north-Indian population with Type 2 diabetes, the overall prevalence of GAD antibodies and the prevalence of either GAD or IA2 antibodies were considerably lower than those reported in white European populations.

Enhanced foamability of sodium dodecyl sulfate surfactant mixed with superspreader trisiloxane-(poly)ethoxylate.

Gravitational drainage from thin vertical surfactant solution films and gravitational drainage in a settler column are used to study the behavior of foams based on two-surfactant mixtures. Namely, solutions of the anionic sodium dodecyl sulfate (SDS) and nonionic superspreader SILWET L-77, and their mixtures at different mixing ratios, are studied. It is shown, for the first time, that solutions having a longer lifetime in the vertical film drainage process also possess a higher foamability. An additional and unexpected unique result is that when using a mixed surfactant system, the foamability can be much greater than the foamabilities of the individual components.

Superspreaders versus "cousin" non-superspreaders: disjoining pressure in gravitational film drainage.

Gravitational drainage of vertical films supported on a wire frame of two superspreaders SILWET L-77 and BREAK-THRU S 278 and their respective "cousin" non-superspreaders SILWET L-7607 and BREAK-THRU S 233 revealed drastic differences. The superspreader films showed complicated dynamic "turbulent"-like interferometric patterns in distinction from the ordered color bands of the "cousin" non-superspreaders, which resembled those of the ordinary surfactants. Nevertheless, the superspreader films stabilized themselves at the thickness about 35 nm and revealed an order of magnitude longer lifetime before bursting compared to that of the "cousin" non-superspreaders. Notably, the superspreaders revealed drastic differences from the non-superspreaders in aqueous solutions with no contact with any solid hydrophobic surface. The self-stabilization of the superspreader films is attributed to significant disjoining pressure probably related to long superspreader bilayers hanging from the free surfaces. The scaling law for the disjoining pressure was found as p(disj)(h) ~ h(-m) (with m ≈ 9-11) for the sufficiently concentrated superspreader solutions, and as p(disj)(h) ~ h(-s) (with s ≈ 6) for more dilute solutions (in both cases, concentrations were above the critical micelle concentration). The non-superspreaders do not possess any significant disjoining pressure even in the films with thicknesses in the 35-100 nm range. The results show that gravitational drainage of vertical films is a useful simple tool for measuring disjoining pressure.

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells.

Curcumin has been shown to inhibit the growth of various types of cancer cells; however, at concentrations much above the clinically achievable levels in humans. The concentration of curcumin achieved in the plasma after oral administration in humans was estimated to be around 1.8 microM. Here, we report that treatment of BxPC-3 human pancreatic cancer cells with a low and single exposure of 2.5 microM curcumin for 24 h causes significant arrest of cells in the G2/M phase and induces significant apoptosis. Immunoblot studies revealed increased phosphorylation of H2A.X at Ser-139 and Chk1 at Ser-280 and a decrease in DNA polymerase-beta level in curcumin-treated cells. Phosphorylation of H2A.X and Chk1 proteins are an indicator of DNA damage whereas DNA polymerase-beta plays a role in the repair of DNA strand breaks. Normal immortalised human pancreatic ductal epithelial (HPDE-6) cells remained unaffected by curcumin treatment. In addition, we also observed a significant increase in the phosphorylation of Chk1 at Ser-345, Cdc25C at Ser-216 and a subtle increase in ATM phosphorylation at Ser-1981. Concomitant decrease in the expressions of cyclin B1 and Cdk1 were seen in curcumin-treated cells. Further, curcumin treatment caused significant cleavage of caspase-3 and PARP in BxPC-3 but not in HPDE-6 cells. Silencing ATM/Chk1 expression by transfecting BxPC-3 cells with ATM or Chk1-specific SiRNA blocked the phosphorylation of ATM, Chk1 and Cdc25C and protected the cells from curcumin-mediated G2/M arrest and apoptosis. This study reflects the critical role of ATM/Chk1 in curcumin-mediated G2/M cell cycle arrest and apoptosis in pancreatic cancer cells.

Uterine artery embolization for symptomatic fibroids with imaging follow up.

The aim of this study was to determine the effectiveness of uterine artery embolization (UAE) as a primary treatment method in treatment of symptomatic fibroids, whether there are any preembolization MRI characteristics of fibroid predictive of reduction in volume and assess reduction in uterine and dominant fibroid volumes using ultrasound (US) and MRI. Study was carried out in total of 32 patients aged 25-49 years (mean 40.9 years). Uterine and dominant fibroid volume were determined using US and MRI before UAE, MRI and US at 3 months and US alone at 6 and 12 months post-UAE, supplemented by clinical evaluation at interval of 3, 6 and 12 months. Procedure was carried out through unilateral femoral puncture using poly vinyl alcohol (PVA) particles 355-500 microm in size. All 32 patients had successful procedures. Overall, 25 patients responded, giving a clinical success rate of 78.12%. Mean reduction in volume of uterus and fibroid was 33 and 59.7% and 48.9 and 75.5% on US at 3 and 12 months respectively, and 33.3 and 58.6% on MRI at 3 months. Volume reduction on US and MRI at 3 months was highly correlative. There was no statistical difference in size reduction in volume of fibroids, which were hypointense or hyperintense on T2-weighted image (T2WI) on pre-UAE MRI. Uterine artery embolization leads to good technical success and fibroid volume reduction. Ultrasound alone may be used for follow up of patients post-UAE. Preprocedure signal characteristics on T2WI are not predictors of volume reduction after UAE.