Fashionable Co-operative Sensing of Bivalent Zn2+ and Cd2+ in Attendance of OAc- by Use of Simple Sensor: Exploration of Molecular Logic Gate and Docking Studies.

The Schiff-base probe H2VL [6,6'-((1E,1'E)-hydrazine-1,2 diylidenebis(methanylylidene))bis(2-methoxyphenol)] is synthesized and structurally characterized by single crystal X-ray diffraction (SCXRD). H2VL is able to detect selectively acetate ion (OAc-) colorimetrically over other anions with 1:1 co-ordination. The detection limit is found to be 4.93 µM. On the other hand, fluorescence intensity of the receptor is drastically enhanced with Zn2+ and Cd2+ in the presence of acetate as counter anion. N, N-Dimethyl formamide (DMF) or Dimethylsulphoxide (DMSO) and acetate (OAc-) was the best solvent and counter anion for Zn2+/Cd2+ -sensing compared with other solvents and anions, respectively. Detection limit for Zn2+ and Cd2+ are calculated to be 1.94 µM and 1.99 µM, respectively. The strong selective emissive behavior could be attributed to the CHEF (chelation-enhanced fluorescence) process. According to the changes in output emission intensity in DMSO in response to the set of ions (Zn2+, Cd2+ and OAc¯) as input variables, the function of 3-input multifunctional molecular logic circuits has been demonstrated. The molecular docking studies of H2VL with DNA and BSA are also performed to confirm its possible bioactivity.

Utility of Fine Needle Aspiration Cytology (FNAC) in the diagnosis of tuberculous lymphadenitis compared to GeneXpert in a tertiary health care center in Northern Odisha, India.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis including tuberculous lymphadenitis (TBLN) is challenging because of its atypical clinical presentation, paucibacillary nature of mycobacteria at the infected sites, variation in sensitivity of a test to specimens collected by different methods and from different infected tissues. METHODS: In the present study, suspected individuals for lymph node tuberculosis irrespective of age were enrolled prospectively and specimens were collected aseptically by fine needle aspiration (FNA). After the implementation of exclusion criteria, FNA specimens from a total of 278 cases of suspected TBLN were evaluated for cytomorphology (FNAC), presence of acid-fast bacillus (AFB) in smear microscopy and specific detection of mycobacterial DNA in cartridge-based nucleic acid amplification test (CBNAAT). RESULTS: The results showed high prevalence of Type II (59.71%), followed by Type I (34.53%) and Type III (5.75%) pattern in FNAC. Non-type II patterns were significantly high in regions outside of the head and neck region (P = 0.031; OR = 2.125) and had an increasing trend of their occurrences with progression of age. The most affected age group was between 16 and 30 years with female preponderance documented in individuals below 45 years, whereas male preponderance was observed in higher age group patients, majority of whom had infected lymph nodes outside of HAN region (P = 0.063, OR = 1.998). The results also showed high sensitivity of CBNAAT (83.04%) method followed by FNAC (72.17%) with AFB smear exhibiting the disappointing results (sensitivity of 10.86%) compared to the CRS. High percentage of positivity was observed in Type III (AFB:25% vs CBNAAT: 100%) followed by Type II (AFB:10.2 vs CBNAAT: 76.5), while low detection was observed from samples with Type I (AFB:4.2 vs CBNAAT: 50). Interestingly, CBNAAT detection of TB was shown to be unaffected by gender, age and site of infection. CONCLUSION: The study suggests a possible contributary role of age and gender for cytomorphological pattern distribution of TBLN at various body parts. Although FNAC detected TB in 77.1% of cases which were identified positive by CBNAAT and/or AFB, it is being solely based on cytomorphology cannot be used alone as a reliable diagnostic method for TBLN detection. Further, the negative results in CBNAAT for FNAC positive cases may not necessarily be non-TB cases and must be evaluated by other diagnostic modalities. We recommend for both cytomorphological investigation and CBNNAT for the fine needle aspirates from suspected TBLN and subsequent treatment to reduce the disease burden.

Hairpin Oligonucleotide Can Functionalize Gold Nanorods for in Vivo Application Delivering Cytotoxic Nucleotides and Curcumin: A Comprehensive Study in Combination with Near-Infrared Laser.

We prepared a multimodality nanocomplex by functionalizing gold nanorods (GNRs) with a cytotoxic nucleoside, 5-fluoro-2'-deoxyuridine (FdU) containing a DNA hairpin, along with complexation of pleiotropic molecule curcumin. Conjugates were investigated for anti-tumor activity using an Ehrlich carcinoma model in combination with 808 nm laser irradiation. We demonstrated that hairpin-functionalized GNRs are suitable for intravenous administration, including delivery of cytotoxic nucleotides and curcumin. Curcumin binding with FdU-hairpin-functionalized GNRs displayed improved anti-tumor activity in part by inducing a lymphocyte-mediated immune response. The complex showed notable photothermal activity in vitro; however, 808 nm laser irradiation of the tumor following treatment with the complex did not increase the anti-tumor effect significantly. Biodistribution studies depicted that the nanoconjugates localized primarily in the sinusoidal structures of the liver and spleen with minimal tumor accumulation. Curcumin complexation alleviated the reduction in the RBC count that was observed for the conjugate without curcumin, especially in combination with laser irradiation. Localization of FdU-hairpin-GNR conjugates in the liver and spleen evoked an inflammatory response, which was mitigated by curcumin complexation. However, no functional abnormality was found in the liver in any case. Curcumin binding also notably decreased nanoconjugate accumulation in lungs and significantly reduced inflammation. Biodistribution studies were consistent with previous reports, suggesting that optimization of the GNR size and surface coating is required for more efficient tumor localization via the enhanced permeability and retention (EPR) effect. Our studies demonstrate that DNA/RNA hairpins are suitable for GNR surface functionalization and enable delivery of cytotoxic nucleotides as well as curcumin in vivo with potential for synergistic anti-cancer therapy.

Encapsulation of Thymol in cyclodextrin nano-cavities: A multi spectroscopic and theoretical study.

Cyclodextrins have a wide range of applications in different areas of drug delivery and pharmaceutical industry due to their complexation ability and other versatile characteristics. Here we have studied the binding interactions of a small biologically important phenolic molecule, Thymol (Th), with both α and ß cyclodextrins (CDs), which are well known drug delivery vehicles. Extent of encapsulation has been determined using several spectroscopic techniques. In fluorescence experiments, significant increase in fluorescence intensities have been discerned for both the CDs but there had been a much early saturation for αCD. Anisotropy experiments have been performed too and very surprisingly no appreciable increase in anisotropy value was observed in either case. Isothermal titration calorimetry (ITC) data, however, show signature of binding of Th with the ßCD. These intriguing results were explained with the help of molecular docking and dynamics simulation studies. The docking calculations have shown that Th goes inside both α and ßCD. In keeping with the final NMR data and molecular dynamics we have ultimately concluded that solvated Th molecules are the main participants in the interaction with CDs which is responsible for these intriguing behaviors. Finally we have also performed an antioxidant assay to reveal the practical application of such encapsulation. It has been found that on encapsulation there is an enhancement of the antioxidant behavior of Th. Then we have also performed an antibacterial assay to show the unchanged antibacterial properties of Th on encapsulation. Hence it can be deduced that Th can be safely delivered through CDs in living system without hampering its beneficial properties.

Secondary Structure-Dependent Physicochemical Interaction of Oligonucleotides with Gold Nanorod and Photothermal Effect for Future Applications: A New Insight.

We investigate the physicochemical interactions of gold nanorod (GNR) with single-stranded, double-stranded, and hairpin DNA structures to improve the biological compatibility as well as the therapeutic potential, including the photothermal effect of the conjugates. Studies have demonstrated that different DNA secondary structures, containing thiol group, have different patterns of physicochemical interaction. Conjugation efficiency of paired oligonucleotides are significantly higher than that of oligonucleotides with naked bases. Furthermore, hairpin-shaped DNA structures are most efficient in terms of conjugation and increased dispersion, with least interference on GNR near-infrared absorbance and photothermal effect. Our conjugation method can successfully exchange the overall coating of the GNR, attaching the maximum number of DNA molecules, thus far reported. Chemical mapping depicted uniform attachment of thiolated DNA molecules without any topological preference on the GNR surface. Hairpin DNA-coated GNR are suitable for intracellular uptake and remain dispersed in the cellular environment. Finally, we conjugated GNR with 5-fluoro-2'-deoxyuridine-containing DNA hairpin and the conjugate demonstrated significant cytotoxic activity against human cervical cancer cell line (KB). Thus, hairpin DNA structures could be utilized for optimal dispersion and photothermal effect of GNR, along with the delivery of cytotoxic nucleotides, developing the concept of multimodality approach.

Association of VDR gene polymorphisms and 22 bp deletions in the promoter region of TLR2Δ22 (-196-174) with increased risk of pulmonary tuberculosis: A case-control study in tea garden communities of Assam.

BACKGROUND: A high number of pulmonary tuberculosis (PTB) cases have been reported from tea garden communities of Assam. Till date, no molecular epidemiological study was performed to investigate the association of candidate gene(s) with the risk PTB in this region. The present case-control study was aimed to investigate the association of vitamin D receptor (VDR) gene polymorphisms and 22 bp deletion in the promoter region of toll-like receptor 2 (TLR2) gene with the risk of PTB in tea garden communities of Assam. METHODS: Genotyping of VDR polymorphisms and TLR2Δ22 (-196-174) gene was carried out for 169 PTB cases and 227 apparently healthy community controls using blood samples by PCR-RFLP followed by DNA sequencing. For association study, both univariate and multivariate logistic regression analyses were performed. RESULTS: This study has shown that BsmI and FokI polymorphisms of VDR gene significantly associated with an increased risk of PTB (AOR = 3.58, 95% CI = 1.64-7.80, P < .01 for B/b genotype of BsmI and AOR = 2.44, 95% CI = 1.40-4.24, P < .01 for F/f genotype of FokI polymorphism). No significant association of TaqI and ApaI polymorphism of VDR gene was found with the risk of PTB. Moreover, this study has revealed that person carrying deletion allele in their TLR2Δ22 (-196-174) gene is significantly associated with an increased risk of PTB having b/b or F/f genotypes in BsmI or FokI polymorphisms of VDR gene. CONCLUSION: This study has revealed that BsmI and FokI polymorphisms of VDR gene significantly associated with an increased risk of PTB.

Curcumin stably interacts with DNA hairpin through minor groove binding and demonstrates enhanced cytotoxicity in combination with FdU nucleotides.

We report, based on biophysical studies and molecular mechanical calculations that curcumin binds DNA hairpin in the minor groove adjacent to the loop region forming a stable complex. UV-Vis and fluorescence spectroscopy indicated interaction of curcumin with DNA hairpin. In this novel binding motif, two É£ H of curcumin heptadiene chain are closely positioned to the A16-H8 and A17-H8, while G12-H8 is located in the close proximity of curcumin α H. Molecular dynamics (MD) simulations suggest, the complex is stabilized by noncovalent forces including; π-π stacking, H-bonding and hydrophobic interactions. Nuclear magnetic resonance (NMR) spectroscopy in combination with molecular dynamics simulations indicated curcumin is bound in the minor groove, while circular dichroism (CD) spectra suggested minute enhancement in base stacking and a little change in DNA helicity, without significant conformational change of DNA hairpin structure. The DNA:curcumin complex formed with FdU nucleotides rather than Thymidine, demonstrated enhanced cytotoxicity towards oral cancer cells relative to the only FdU substituted hairpin. Fluorescence co-localization demonstrated stability of the complex in biologically relevant conditions, including its cellular uptake. Acridine orange/EtBr staining further confirmed the enhanced cytotoxic effects of the complex, suggesting apoptosis as mode of cell death. Thus, curcumin can be noncovalently complexed to small DNA hairpin for cellular delivery and the complex showed increased cytotoxicity in combination with FdU nucleotides, demonstrating its potential for advanced cancer therapy.

Cervical strongyloidiasis in an immunocompetent patient: A clinical surprise.

A 32-year-old lady came for a routine gynecological check up. Her cervical cytologic smear was reported as low grade squamous intraepithelial lesion. As a part of basic routine investigation, cervical punch biopsy was done. Astonishingly it revealed multiple rhabditiform larvae of Strongyloides stercoralis. These were curved thick with pointed end and a short buccal cavity. She did not have any history of immunosuppression including steroid therapy and was otherwise normal. Extensive review of the literature on parasites encountered in cervix yielded few case reports on strongyloides in cytologic smears, but failed to reveal any report till date on S. stercoralis found in histopathology section. Our case is probably the first in the world and the first reported from India to the best of our knowledge. We describe this case of strongyloidiasis of cervix with review of the literature on various parasites encountered in the cervix because of its rarity and also to keep this parasitic infestation as a differential diagnosis of cervical lesions.

Cytodiagnosis of metastatic Ewing's sarcoma of orbital mass and its confirmation by demonstration of EWS/friend leukemia integration 1 fusion gene.

Ewing's sarcoma (EWS) is an undifferentiated sarcoma of bone. Its morphologic appearance resembles many other malignant small round cell tumors. Due to the morphologic overlap, there is diagnostic difficulty and for accurate diagnosis, requires special studies such as immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. We report a case of metastatic EWS from orbital mass in a 14-year-old female child diagnosed by cytology after clinicopathologic evaluation. She presented with low back ache of 1 year followed by proptosis of the right eye and swelling of the right side chest wall. Cytosmear and Tru-cut biopsy was taken from the orbital mass showed features of EWS. It was confirmed later by further studies including demonstration of EWS/friend leukemia integration-1 fusion gene by molecular genetic analysis.

New mass limit for white dwarfs: super-Chandrasekhar type ia supernova as a new standard candle.

Type Ia supernovae, sparked off by exploding white dwarfs of mass close to the Chandrasekhar limit, play the key role in understanding the expansion rate of the Universe. However, recent observations of several peculiar type Ia supernovae argue for its progenitor mass to be significantly super-Chandrasekhar. We show that strongly magnetized white dwarfs not only can violate the Chandrasekhar mass limit significantly, but exhibit a different mass limit. We establish from a foundational level that the generic mass limit of white dwarfs is 2.58 solar mass. This explains the origin of overluminous peculiar type Ia supernovae. Our finding further argues for a possible second standard candle, which has many far reaching implications, including a possible reconsideration of the expansion history of the Universe.