MOLECULAR DYNAMICS STUDY OF NON-HYDROGEN-BONDING BASE-PAIR DNA DUPLEX d(GTCDNAM GCGCCGTGGC). d(GCCACGGCGCD5SICSGAC)

Objective: The objective of the study was to elucidate the structural activity of a natural DNA sequence modified by a hydrophobic base-pair which didn't form Watson-Crick (W-C) hydrogen-bond. The modified unnatural base-pair (DNAM-D5SICS) was introduced in DNA sequences of 14-mer for molecular dynamics study in water solution.Methods: A 200 ns molecular-dynamics-simulation in orthogonal-box-water-solvent, using Particle-mesh-Ewald-method (PME) within periodic-boundary-condition (PBC) was performed by using AMBER-14 code. The force-field-ff12SB-force-field was used during the simulation while the force-field-parameters of modified base-pair, compatible to ff12SB-force-field, were calculated by Gaussian-09-code using ab-inito/Hartree-Fock-methodology. The code CPPTRAJ, (a module of AMBER-14) CURVE and Chimera were used in the analysis of the data.Results: Root mean square deviation (RMSD) of heavy atoms of the trajectory revealed that the structure of the equilibrated duplex was stable, sequence-dependent and had mixed DNA-conformation. A little distortion near to the neighbor of the modified base-pair in the duplex strand was observed. However, we got a stabilized structure of such type of duplex if we placed modified base-pair after the third place in the strand.Conclusion: The study concluded that the distortion produced by modified-base-pair in the overall structure of duplex was local while the confirmation of such type of duplex was mixed and maintained the Watson-Crick (W-C) integrity of DNA. The study would help in the use of hydrophobic base-pair materials in biotechnological applications and the understanding of their structure-function relationship

A Study on Phylogenetic Analysis of Fishes in the Sone River of Sidhi District, Madhya Pradesh (India)

The Sone River is a significant river in India, located primarily in the states of Madhya Pradesh, Uttar Pradesh, and Bihar. It is one of the major tributaries of the Ganges River and plays a crucial role in the region's ecology, economy, and cultural heritage. In the present study 1000 individuals of fish specimens were collected from four different geographical locations of Sone River of Sidhi district region. Morphologically 19 species were identified and Phylogenetic trees were constructed based on CO1 gene of mitochondrial DNA using Maximum Parimony approaches using MEGA 11 software. The Phylogenetic tree revealed that species clustered differently under diverse nodes. It revealed that fish species clustered together because they were in the same order and family. These results showed that fish species share identical genera but with diverse genetic variations due to diverse habitats involving a common ancestor

A study to assess body mass index and pattern of physical activity among the government employees working at different organizations of Gwalior city

Background: The obesity can be defined simply as the disease in which excess body fat has accumulated to such an extent that health may be adversely affected. Physical activity is a key determinant of energy expenditure, and thus is fundamental to energy balance and weight control. Aims and objectives was to assess the BMI and physical activity among government employees working in different organizations of Gwalior city.Methods: The present study was a cross sectional study. Five different government organizations were selected and from each organization 60 participants were selected randomly. A pre-designed, pre-tested, semi-structured interview based questionnaire was used for data collection from different participants. WHO BMI classification was used to classify participants.Results: In the present study 44% of the study participants were overweight/ pre-obese while 8.33% and 1.33% were in Obese Class I and Obese Class II respectively. 40.67% were doing physical exercise. The most common type of physical exercise was walking or jogging 72.13%.Conclusions: It was concluded that despite the known fact that obesity could have negative impact on the work capacity and physical fitness, only 40.67% were doing some physical exercise. Employees should be motivated to do daily exercise for the duration of at least 30 minutes

Combination of Amphiphilic Cyclic Peptide [R\u3csub\u3e4\u3c/sub\u3eW\u3csub\u3e4\u3c/sub\u3e] and Levofloxacin against Multidrug-Resistant Bacteria

Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R4W4] containing arginine (R) and tryptophan (W) with a MIC of 2.67 µg/mL (1.95 µM) against methicillin-resistant Staphylococcus aureus (MRSA). Herein, we investigated the cyclic peptides [R4W4] or linear (R4W4) and their conjugates (covalent or noncovalent) with levofloxacin (Levo) with the intent to improve their potency to target drug-resistant bacteria. The physical mixture of the Levo with the cyclic [R4W4] proved to be significantly effective against all strains of bacteria used in the study as compared to covalent conjugation. Furthermore, the checkerboard assay revealed the significant synergistic effect of the peptides against all studied strains except for the wild type S. aureus, in which the partial synergy was observed. The hemolysis assay revealed less cytotoxicity of the physical mixture of the Levo with [R4W4] (22%) as compared to [R4W4] alone (80%). The linear peptide (R4W4) and the cyclic [R4W4] demonstrated ~90% and 85% cell viability at 300 µg/mL in the triple-negative breast cancer cells (MDA-MB-231) and the normal kidney cells (HEK-293), respectively. Similar trends were also observed in the cell viability of Levo-conjugates on these cell lines. Furthermore, the time-kill kinetic study of the combination of [R4W4] and Levo demonstrate rapid killing action at 4 h for MRSA (ATCC BAA-1556) and 12 h for E. coli (ATCC BAA-2452), P. aeruginosa (ATCC BAA-1744), and K. pneumoniae (ATCC BAA-1705). These results provide the effectiveness of a combination of Levo with cyclic [R4W4] peptide, which may provide an opportunity to solve the intriguing puzzle of treating bacterial resistance

FORMULATION AND CHARACTERIZATION OF FLOATING TABLET DOSAGE FORM OF DUAL DELIVERY OF DRUG CURCUMIN AND BERBERINE HYDROCHLORIDE USING SIMULTANEOUS ESTIMATION BY UV SPECTROSCOPY

Objective: The present study was aimed to develop a combinational floating tablet of curcumin and berberine HCl utilizing synthetic polymers synthetic HPMC K-15M and evaluate its various characteristics. Methods: The formulations were developed by the process of wet granulation and evaluated for drug content, content uniformity, floating lag time, total floating time, in vitro buoyancy studies, and in vitro drug release profile. A simultaneous estimation method for curcumin and berberine was developed using U. V spectroscopy. Results: The results clearly indicated that the tablets produced were having acceptable physical parameters. The absence of any drug/polymer/excipient interactions was confirmed using infrared spectroscopy. It was found that the drug content of was in between 96.22 to 99.45 % in all the formulations. Because of their low densities, in vitro floatability tests showed that most of the tablets floated for more than 8 h. The in vitro release studies confirmed the sustained release of more than 80 percent of drug contained within a period of 8 h. In vitro buoyancy was good in all three batches (F1-F3). The overall floating time for the F2 formulation was 24 h. After one month of storage at 40 °C and 75 percent RH, the F2 formulation showed no noticeable change in physical as well as pharmaceutical performance characteristics. Conclusion: Floating tablets of curcumin and berberine was successfully developed and had passed on various pharmaceutical parameters

[(WR)\u3csub\u3e8\u3c/sub\u3eWKβA]-Doxorubicin Conjugate: A Delivery System to Overcome Multi-Drug Resistance against Doxorubicin

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]9 containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)8WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the corresponding physical mixture of the peptide and Dox to evaluate the effectiveness of synthesized conjugate compared to the parent drug alone. [(WR)8WKβA]-Dox conjugate showed higher antiproliferative activity at 10 µM and 5 µM than Dox alone at 5 μM. The conjugate inhibited the cell viability of ovarian adenocarcinoma (SK-OV-3) by 59% and the triple-negative breast cancer cells MDA-MB-231 and MCF-7 by 71% and 77%, respectively, at a concentration of 5 μM after 72 h of incubation. In contrast, Dox inhibited the proliferation of SK-OV-3, MDA-MB-231, and MCF-7 by 35%, 63%, and 57%, respectively. Furthermore, [(WR)8WKβA]-Dox conjugate (5 µM) inhibited the cell viability of Dox-resistant cells (MES-SA/MX2) by 92%, while the viability of cells incubated with free Dox was only 15% at 5 μM. Confocal microscopy images confirmed the ability of both Dox conjugate and the physical mixture of the peptide with the drug to deliver Dox through an endocytosis-independent pathway, as the uptake was not inhibited in the presence of endocytosis inhibitors. The stability of Dox conjugate was observed at different time intervals using analytical HPLC when the conjugate was incubated with 25% human serum. Half-life (t1/2) for [(WR)8WKβA]-Dox conjugate was (∼6 h), and more than 80% of the conjugate was degraded at 12 h. The release of free Dox was assessed intracellularly using the CCRF-CEM cell line. The experiment demonstrated that approximately 100% of free Dox was released from the conjugate intracellularly within 72 h. These data confirm the ability of the cyclic cell-penetrating peptide containing tryptophan and arginine residues as an efficient tool for delivery of Dox and for overcoming resistance to it

Mercury or Mercury Free Restorations in Oral Cavity

Amalgam is basically a concoction of metals that has been used as a potent filling material in dentistry for the last 150 years. Amalgam usually consists of silver, mercury, tin and copper. Dental amalgam is a material used to fill cavities of tooth. Over the years, amalgam has become a topic of concern because it contains mercury. Mercury is a naturally occurring metal in the environment. Mercury exists as a liquid in room temperature but when heated, it becomes a gas. Flexibility of amalgam as a filling material is due Mercury. An alloy powder, a compound that is soft in nature when mixed with mercury makes it enough to mix and condense into the tooth. It hardens quickly and offers strong resistance to the forces of biting and chewing. There are studies reported on the safety of amalgam fillings. In 2005, European Union launched a comprehensive mercury strategy to reduce use of mercury. In 2008, countries like Norway and Denmark restricted the use of dental amalgam containing mercury. In 2009, this research was evaluated by U.S. Food and Drug Administration (FDA) and found no rationale to limit the use of amalgam.  There are certain restorative materials that are available commercially that are mercury free in nature like Gold, Porcelain, Gallium alloys, Composite resin restoratives etc. They offer many advantages over amalgams containing mercury like: seals the dentin from future decay, reinforces remaining tooth structure, provides smooth and bonded margins, conservative and it blends naturally

Click chemistry inspired one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles and their Src kinase inhibitory activity

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure–activity relationship analysis demonstrated that insertion of C6H5– and 4-CH3C6H4– at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32–43 μM) of 1,4-disubstituted 1,2,3-triazoles. [Refer to PDF for graphical abstract

Ghost diffraction: A spatial statistical approach

We report the reconstruction of a transparency image in Ghost diffraction scheme using a statistical optics approach. This is implemented by using a static diffuser rather than a pseudo thermal light source with a rotating diffuser. The experimental implementation makes use of spatial ergodicity and spatial stationarity for spatially distributed random fields. A strategy to realize the Ghost diffraction scheme through spatial intensity correlation with a phase retrieval algorithm permits reconstruction of the transparency