Molecular docking study on vitamin D supplements to understand their interaction with VDR-RXRα heterodimer and VDRE of TAGAP gene.

The expression level of T cell activation Rho GTPase activating protein (TAGAP) gene is higher in rheumatoid arthritis (RA) patients compared to healthy individuals. Vitamin D receptor element (VDRE) sequences present in the regulatory region of TAGAP gene are targeted by vitamin D dependent Vitamin D receptor (VDR) - retinoic acid X receptor (RXR) heterodimer complex to regulate the TAGAP gene expression. Reduction in the expression of the TAGAP gene can prevent different severity of RA disease conditions. Calcitriol is a proven vitamin D supplement prescribed to patients with RA. However, it is involved in causing hypercalcemia. Maxacalcitol, an analog of vitamin D, is shown to have less hypercalcemic activity when compared to calcitriol. This study was done to analyze and compare the binding modes of calcitriol and maxacalcitol with VDR. We also studied the interactions of these compounds with the VDR-RXRα heterodimer complex. In addition, the binding of the ligand-activated heterodimer complexes with VDREs of the TAGAP gene was also analyzed to comprehend the binding affinities of calcitriol and maxacalcitol to the gene. The current work utilizes in silico molecular docking and simulation analysis to understand the mechanism in each complex formation.Communicated by Ramaswamy H. Sarma.

The pattern of tobacco use and the associated socio-demographic factors among Transgenders living in Chennai city of Tamil Nadu, India.

Introduction: The tobacco epidemic is one of the biggest public health threats the world has ever faced, which kills more than 8 million people a year around the world. Transgenders are prone to use and abuse substances including tobacco and alcohol as a coping mechanism to manage minority stress experienced due to high levels of discrimination and lack of acceptance by society. Objectives: Among transgenders living in Chennai city, Tamil Nadu, (1) we aimed to estimate the prevalence and describe the pattern of tobacco use and (2) identify the sociodemographic factors associated with tobacco use. Methods: A community-based cross-sectional analytical study was conducted among 734 transgender adults living in the Chennai city of Tamil Nadu. A pre-tested, semi-structured interview schedule was used. Descriptive statistics such as frequency and proportions were used for categorical variables. Chi-square test was applied to find the significance of the association between tobacco use and sociodemographic factors. Results: The prevalence of the current use of any form of tobacco products among transgenders was 64.4%. About 27% had tried to stop using tobacco during the past 1 year. Education status, socioeconomic class, and occupation were significantly associated with the current use of any form of tobacco and trying to quit tobacco use. Conclusion: The prevalence of tobacco use among transgenders is alarming. The present study findings highlight the need to increase awareness activities by health authorities and non-government organizations (NGOs)/community-based organizations (CBOs) to generate awareness about the health hazards of tobacco use among transgenders. Tobacco control programs focussing on transgenders are essential.

Effect of Aromatherapy on Dental Anxiety Among Orthodontic Patients: A Randomized Controlled Trial.

INTRODUCTION: Dental anxiety is a distressing challenge faced by both the patients and the dental care provider, particularly in the Department of Orthodontics. The goal of this study was to assess the effect of aromatherapy (oils) on dental anxiety level among orthodontic patients and to compare the effect on anxiety levels between lavender oil, rose oil, and a placebo. MATERIALS AND METHODS: A total of 72 patients (36 men and 36 women) who reported to the Department of Orthodontics were selected and randomly allocated into three groups: lavender oil, rose oil, and placebo. The ambient odor of those oils or placebo was maintained with a candle warmer, and the patients were made to wait in their respective rooms for 15 minutes. Participants' heart rate and blood pressure, being reliable and objective indicators of anxiety, were measured using pulse oximeter and sphygmomanometer, respectively. Additionally, a questionnaire, comprising demographic data and questions representing a modified Dental Anxiety Scale, was given to the patients to measure subjective anxiety levels before and after aromatic therapy. Paired t-test, analysis of variance, and the Wilcoxon signed-rank test were used for both subjective and objective analyses. RESULTS: Lavender oil and rose oil produced a significant reduction of dental anxiety level among orthodontic patients in both objective and subjective method (P ≤ .05); lavender oil demonstrated a greater significance in reducing the anxiety level when compared to rose oil. CONCLUSION: Our findings indicate that aromatherapy offers promising effect against dental anxiety among orthodontic patients. Aromatherapy can be recommended as an easy alternative to reduce anxiety in patients before orthodontic treatment.

Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates.

Despite zinc oxide nanoparticles (ZnONPs) being increasingly used as carriers in biomedical fields due to their multifaceted properties and therapeutic importance, better understanding of the mechanisms and cellular consequences resulting from their interaction with cells and cellular components has been warranted. In the present study, we investigate the size-dependent interaction of ZnONPs on RBCs, and its impact on cell viability, DNA damage, ROS generation and morphological changes, employing cellular and analytical methods. Size, charge, stability and solubility were confirmed by DLS, zeta potential, ICP-AES and TEM analysis. Further ICP-AES, TEM, spectroscopic observations and cell based assays showed that ZnONPs exhibited a size dependent impact on RBCs and haemoglobin (Hb), particularly size <50 nm. Conversely, ferulic acid (FA) conjugates and serum albumin significantly reduced the adverse effects exhibited by ZnONPs. The extent of DNA damage and ROS generation is comparatively low in ZnONPs-FA than in ZnONPs alone treated cells. Thus our study documents a novel conceptualization delineating the influence of size on the material properties and therapeutic potential of nanoparticle.

Studies on the synthesis, characterization, human serum albumin binding and biological activity of single chain surfactant-cobalt(III) complexes.

The interaction of surfactant-cobalt(III) complexes [Co(bpy)(dien)TA](ClO4)3 · 3H2O (1) and [Co(dien)(phen)TA](ClO4)3 · 4H2O (2), where bpy = 2,2'-bipyridine, dien = diethylenetriamine, phen = 1,10-phenanthroline and TA = tetradecylamine with human serum albumin (HSA) under physiological conditions was analyzed using steady state, synchronous, 3D fluorescence, UV/visabsorption and circular dichroism spectroscopic techniques. The results show that these complexes cause the fluorescence quenching of HSA through a static mechanism. The binding constant (Kb ) and number of binding-sites (n) were obtained at different temperatures. The corresponding thermodynamic parameters (∆G°, ∆H° and ∆S°) and Ea were also obtained. According to Förster's non-radiation energy transfer theory, the binding distance (r) between the complexes and HSA were calculated. The results of synchronous and 3D fluorescence spectroscopy indicate that the binding process has changed considerably the polarity around the fluorophores, along with changes in the conformation of the protein. The antimicrobial and anticancer activities of the complexes were tested and the results show that the complexes have good activities against pathogenic microorganisms and cancer cells.

Biological and protein-binding studies of newly synthesized polymer-cobalt(III) complexes.

The polymer-cobalt(III) complexes, [Co(bpy)(dien)BPEI]Cl3 · 4H2O (bpy = 2,2'-bipyridine, dien = diethylentriamine, BPEI = branched polyethyleneimine) were synthesized and characterized. The interaction of these complexes with human serum albumin (HSA) and bovine serum albumin (BSA) was investigated under physiological conditions using various physico-chemical techniques. The results reveal that the fluorescence quenching of serum albumins by polymer-cobalt(III) complexes took place through static quenching. The binding of these complexes changed the molecular conformation of the protein considerably. The polymer-cobalt(III) complex with x = 0.365 shows antimicrobial activity against several human pathogens. This complex also induces cytotoxicity against MCF-7 through apoptotic induction. However, further studies are needed to decipher the molecular mode of action of polymer-cobalt(III) complex and for its possible utilization in anticancer therapy.

An unusual case of cervical lipoblastoma with review of literature.

Lipoblastoma is a rare, benign, soft tissue neoplasm most commonly seen in children less than 3 years. It is usually seen on the trunk and on the limbs and rarely in the head and neck. In our case, a child of age 1 year and 3 months presented with a swelling over the nape of the neck. The swelling had rapidly increased in size and was associated with difficulty in neck movements. Intraoperatively it was found to have very minimal adhesions to the underlying muscles of neck. Histopathological examination confirmed it to be a lipoblastoma. The swelling was removed by wide excision, and there was no postoperative complication.

Green synthesis and characterization of selenium nanoparticles and its augmented cytotoxicity with doxorubicin on cancer cells.

Green synthesis of selenium nanoparticles (SeNPs) was achieved by a simple biological procedure using the reducing power of fenugreek seed extract. This method is capable of producing SeNPs in a size range of about 50-150 nm, under ambient conditions. The synthesized nanoparticles can be separated easily from the aqueous sols by a high-speed centrifuge. These selenium nanoparticles were characterized by UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and elemental analysis by X-ray fluorescence spectrometer (XRF). Nanocrystalline SeNPs were obtained without post-annealing treatment. FTIR spectrum confirms the presence of various functional groups in the plant extract, which may possibly influence the reduction process and stabilization of nanoparticles. The cytotoxicity of SeNPs was assayed against human breast-cancer cells (MCF-7). It was found that SeNPs are able to inhibit the cell growth by dose-dependent manner. In addition, combination of SeNPs and doxorubicin shows better anticancer effect than individual treatments.

Biogenic silver nanoparticles for cancer treatment: an experimental report.

A generation of nanoparticles research has discussed recently. It is mandatory to elaborate the applications of biogenic nanoparticles in general and anticancereous property in particular. The present study was aimed to investigate the in vitro cytotoxicity effect of biogenic silver nanoparticles (AgNPs) against human breast cancer (MCF-7) cells towards the development of anticancer agent. Biogenic AgNPs were achieved by employing Sesbania grandiflora leaf extract as a novel reducing agent. It was well characterized by FESEM, EDAX and spectral studies showed spherical shaped nanoparticles in the size of 22 nm in slightly agglomerated form. It was surprising that biogenic AgNPs showed cytotoxic effect against MCF-7 cell lines were confirmed by MTT, AO-EB, Hochest and COMET assays. There was an immediate induction of cellular damage in terms of loss of cell membrane integrity, oxidative stress and apoptosis were found in the cell which treated with AgNPs. This may be a first report on anti-MCF-7 property of biogenic AgNPs in the fourth generation of nanoparticles research. It is necessary to study the formulation and clinical trials to establish the nano drug to treat cancer cells.

Photocatalytic degradation of methyl orange dye using silver (Ag) nanoparticles synthesized from Ulva lactuca.

In this paper, we report on biosynthesis of silver nanoparticles using Ulva lactuca (seaweed) at room temperature along with photocatalytic degradation of methyl orange dye. UV spectral analysis showed peak at 430 nm with special reference to the excitation of surfaces plasmon vibration by silver nanoparticles. FT-IR studies reveal the presence of bioactive functional groups such as phenolic compounds, amines and aromatic ring are found to be the capping and stabilizing agents of nanoparticles. The morphology of silver nanoparticles was found to be spherical and ranges about 48.59 nm as confirmed by HR-SEM. Negative zeta potential value of -34 mV suggests that the nanoparticles are highly stable in colloidal solution. XRD patterns also suggest the occurrence of spherical shaped particles due to the presence of silver ions. Further, photocatalytic degradation of methyl orange was measured spectrophotometrically by using silver as nanocatalyst under visible light illumination. The results revealed that biosynthesized silver nanoparticles using U. lactuca was found to be impressive in degrading methyl orange.

The extra cellular synthesis of gold and silver nanoparticles and their free radical scavenging and antibacterial properties.

The bio reduction of chloro auric acid (HAuCl(4)) and silver nitrate (AgNO(3)) is achieved extracellularly by using the aqueous extract of Solanum torvum (S. torvum) fruit. The nanoparticle formation was screened by UV-visible spectroscopy through color conversion due to surface plasma resonance bands at 560 nm and 430 nm for gold and silver nanoparticles respectively. The spherical shapes with smooth surface of gold and silver nanoparticles were analyzed through scanning electron microscope and its presence was confirmed by energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups in the gold and silver salts and the bio interactive functional groups present in the S. torvum extract were characterized by employing Fourier transform infra-red spectroscopy (FTIR). The biomedical properties of gold and silver nanoparticles were premeditated as free radical scavenging activity and antibacterial static agents. Gold and silver nanoparticles serve as strong hydroxyl, superoxide, nitric oxide and DPPH radical scavengers in contrast to their corresponding metal oxides. The radical quenching properties of gold and silver nanoparticles were found to correlate with in vitro DNA protective effect. The silver nanoparticles show strong zone of inhibition against Escherichia coli, Pseudomonas and Bacillus whereas, gold nanoparticles exhibit fair zone of inhibition. To our knowledge this is the first report that S. torvum extract can reduce metal acids to nano materials.

Sodium selenite enhances glutathione peroxidase activity and DNA strand breaks in hepatoma induced by N-nitrosodiethylamine and promoted by phenobarbital.

An element/compound that acts as an antioxidant as well as, can increase the oxidative stress offers a new approach in differentiation therapy. Experiments were carried out to determine the effect of selenite on DNA damage and glutathione peroxidase (GPx) activity in N-nitrosodiethylamine (DEN) induced, phenobarbital promoted rat hepatoma. Supra-nutritional level of selenite (4 ppm) was supplemented at either, before-initiation/after-initiation and/or during entire period of the study. At the end of experiment period (20 weeks), extent of DNA damage (alkaline comet assay), selenium concentration, and GPx activity were assessed on nodular tissue (NL) cells, surrounding liver (SL) cells, and whole liver tissue (control) cells. Hepatic selenium level and GPx activity were decreased in DEN and PB-administered animals, whereas the DNA damage was found to be increased in both NL and SL cells compared with control group. However, the DNA damage is more in SL cells than in NL cells. Pre-supplementation of selenite did not show any difference in DNA (strand breaks) damage, selenium, and GPx activity. Increased hepatic selenium concentration and GPx activity were observed in both NL and SL cells in post-supplementation and entire period of selenite supplemented animals compared to DEN + PB treated animals. However, DNA damage was increased in NL but decreased in SL cells. Supplementation of selenite alone for 16 or 20 weeks had shown increased DNA damage, selenium concentration, and GPx activity compared to normal control animals. In summary, cancer bearing animals increased DNA damage and decreased Se level and GPx activity in NL and SL cells and other organs in cancer bearing animals, supplementation of Se further provoked DNA damage (no change in pretreatment) in NL cells, however it decreased DNA damage SL cells and other organs (kidney, lungs, and spleen). On the other hand Se levels and GPx activity were increased in NL and SL cells and other organs of Se-supplemented rats (no difference in group 3 animals). These results demonstrate that, in addition to chemopreventive and chemotherapeutic role of selenite, it also prevents cellular DNA damage induced in cancerous condition.

Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice.

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and anti-tumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin-C (MMC)--using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.

The inhibitory effect of sodium selenite on N-nitrosodiethylamine-induced and phenobarbital promoted liver tumourigenesis in rats based on the modulation of polyamine levels.

In the present study, we have evaluated the effects of dietary selenite (Se) on polyamine levels and its influence on N-nitrosodiethylamine (DEN) initiated and Phenobarbital (PB) promoted in rat liver carcinogenesis. Dietary selenite at a concentration of 4 ppm (through drinking water) was administered in rats either before initiation (4 weeks), or during promotion (16 weeks) and entire experimental period (20 weeks). Male Wistar strain of albino rats was treated with single intra peritoneal dose of DEN (200 mg kg(-1) body weight), after 2 weeks the carcinogenic effect was promoted by PB (0.05%; through diet). Alpha fetoprotein (AFP) was investigated after the 20th-week of experimental period. Selenite-treated animals markedly reduced the AFP during the time of pre-selenite [before initiation (4 weeks)] and entire experimental period (20 weeks), administration rather than the promotion period. This infers that anticancer property of selenite depends on the stage of carcinogenesis, rather than duration of treatment. Evaluation of polyamine levels in hepatoma and surrounding liver tissue showed significant difference in the selenite-treated groups compared with pair-fed control groups. Furthermore, histopathological examination showing remarkable difference between control and treated groups. These results demonstrate that selenite can modulate the development of DEN-induced and PB-promoted rat liver carcinogenesis through a polyamine-dependent mechanism.

Protective effect of Spirulina fusiformis on chemical-induced genotoxicity in mice.

Spirulina fusiformis given by oral route to mice at doses of 250, 500 and 1000 mg kg(-1) significantly inhibit the genotoxicity induced by cisplatin and urethane. In addition, a significant reduction in the extent of lipid peroxidation with concomitant increase in the liver enzymatic (GPx, GST, SOD, CAT) and non-enzymatic (reduced glutathione) antioxidants were observed.

Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice.

The modifying effects of the aqueous extract of saffron (dried stigmas of Crocus sativus Linn.) on cisplatin (CIS), cyclophosphamide (CPH), mitomycin-C (MMC) and urethane (URE) induced alterations in lipid peroxidation and antioxidant status were investigated in Swiss albino mice. Three doses of saffron (20, 40 and 80 mg/kg body weight) were orally administered to mice for 5 consecutive days prior to administration of genotoxins. A significant reduction in the extent of lipid peroxidation with a concomitant increase in the liver enzymatic (SOD, CAT, GST, GPx) and non-enzymatic antioxidants (reduced glutathione) were observed in saffron pretreated animals compared with the genotoxins alone treated animals. However, the modulatory effects were not always dose dependent. Our data suggest that saffron may exert its chemopreventive effects by modulation of lipid peroxidation, antioxidants and detoxification systems.

Effect of Spirulina fusiformis on cyclophosphamide and mitomycin-C induced genotoxicity and oxidative stress in mice.

Spirulina fusiformis was tested for its possible in vivo protective effects against cyclophosphamide (CP) and mitomycin-C (MMC) induced genotoxicity and oxidative stress in mice. Pre-treatment with S. fusiformis (250, 500 and 1000 mg kg(-1), p.o., daily for 5 days) significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems. All the three tested doses were effective in exerting a protective effect against CP and MMC.

Inhibition of genotoxicity by saffron (Crocus sativus L.) in mice.

Experiments were carried out to ascertain whether or not saffron (dried stigmas of Crocus sativus L.), a commonly used agent for flavoring and coloring food can exert modulatory effects on the in vivo genotoxicity of cisplatin (CIS), cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE). For this purpose, Swiss albino mice were pretreated for five consecutive days with three doses (20, 40 and 80 mg/kg body weight) of the aqueous extract of saffron. Genotoxic effects were assessed in the mouse bone marrow micronucleus test. The results obtained suggest that pretreatment with saffron can significantly inhibit the genotoxicity of CIS, CPH, MMC and URE. This inhibitory effect was not always dose-dependent. In addition, the hepatic glutathione S-transferase (GST) activity was assessed in the control and treated animals. No significant change in GST activity was observed after pretreatment with saffron alone. Treatment with the genotoxins alone significantly inhibited GST activity. Saffron pretreatment attenuated the inhibitory effects of the genotoxins on GST activity.