Hetero-Diels-Alder and CuAAC Click Reactions for Fluorine-18 Labeling of Peptides: Automation and Comparative Study of the Two Methods.

Radiolabeled peptides are valuable tools for diagnosis or therapies; they are often radiofluorinated using an indirect approach based on an F-18 prosthetic group. Herein, we are reporting our results on the F-18 radiolabeling of three peptides using two different methods based on click reactions. The first one used the well-known CuAAC reaction, and the second one is based on our recently reported hetero-Diels-Alder (HDA) using a dithioesters (thia-Diels-Alder) reaction. Both methods have been automated, and the 18F-peptides were obtained in similar yields and synthesis time (37-39% decay corrected yields by both methods in 120-140 min). However, to obtain similar yields, the CuAAC needs a large amount of copper along with many additives, while the HDA is a catalyst and metal-free reaction necessitating only an appropriate ratio of water/ethanol. The HDA can therefore be considered as a minimalist method offering easy access to fluorine-18 labeled peptides and making it a valuable additional tool for the indirect and site-specific labeling of peptides or biomolecules.

Formulation of herbal based hair colour from Phyllanthus reticulatus.

Synthetic oxidative hair dyes available in the market contain a combination of peroxide and ammonia. In addition, people who use synthetic dyes are at risk for skin burns, irritation to the eye and also lead to cancer. Hence, herbal-based hair dyes are safe to use. In the traditional system of medicine, different parts of Phyllanthus reticulatus were used for curing various ailments. The aqueous leaf extract showed the presence of phytochemical rich components. Herbal hair dye has been formulated by using P. reticulatus with various natural ingredients in the ratio of 5:1:1:1:1. The herbal hair dye was evaluated for its various parameters. It showed potent in vitro antimicrobial activity against various microorganisms and antioxidant activity. In the formulated product, the natural ingredients are known for their non-toxic properties and there are no added chemicals and preservatives. It offers a natural alternative, that can be used irrespective of any side effects.

Pharmacological Prospects of Morin Conjugated Selenium Nanoparticles-Evaluation of Antimicrobial, Antioxidant, Thrombolytic, and Anticancer Activities.

Abstract: Selenium nanoparticles (SeNPs) have gained wide importance in the scientific community and have emerged as an optimistic therapeutic carrier agent for targeted drug delivery. In the present study, the effectiveness of nano selenium conjugated with Morin (Ba-SeNp-Mo) produced from endophytic bacteria Bacillus endophyticus reported in our earlier research was tested against various Gram-positive, Gram-negative bacterial pathogens and fungal pathogens that showed good zone of inhibition against all selected pathogens. Antioxidant activities of these NPs were studied by 1, 1-diphenyl-2- picrylhydrazyl (DPPH), 2,2'-Azino-bis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS), hydrogen peroxide (H2O2), superoxide (O2-), and nitric oxide (NO) radical scavenging assays that exhibited dose-dependent free radical scavenging activity with IC50 values 6.92 ± 1.0, 16.85 ± 1.39, 31.60 ± 1.36, 18.87 ± 1.46, and 6.95 ± 1.27 µg/mL. The efficiency of DNA cleavage and thrombolytic activity of Ba-SeNp-Mo were also studied. The antiproliferative effect of Ba-SeNp-Mo was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in COLON-26 cell lines that resulted in IC50 value of 63.11 µg/mL. Further increased intracellular reactive oxygen species (ROS) levels up to 2.03 and significant early, late and necrotic cells were also observed in AO/EtBr assay. CASPASE 3 expression was upregulated to 1.22 (40 µg/mL) and 1.85 (80 µg/mL) fold. Thus, the current investigation suggested that the Ba-SeNp-Mo has offered remarkable pharmacological activity.

Characterization, Antimicrobial and Antioxidant Evaluation of Biofabricated Silver Nanoparticles from Endophytic Pantoea anthophila.

Endophyte mediated nanoparticles fabrication were emerging as a new frontier in nanomedicines that produce high biocompatible and functionalized silver nanoparticles. In this study, silver nanoparticles were successfully biosynthesized from the extracellular extract of endophytic bacterium Pantoea anthophila isolated from the stem of Waltheria indica for the first time. The synthesized nanoparticles showed a strong absorption band at 410 nm in the UV-Visible range. The dynamic light scattering and zeta potential analysis indicated that the average particle size was 16 nm at 5.30 mV. FTIR spectrum displayed the presence of various functional groups at 3423.65, 1633.71, 1022.27, 607.58 cm-1 that stabilised the nanoparticle. X-ray diffraction peaks were conferred to 100, 200, 220 and 311 planes of a face centred cubic structure. TEM and SEM micrograph revealed the spherical-shaped, polycrystalline nature with the presence of elemental silver analysed by EDAX. Selected area electron diffraction also confirms the orientation of silver nanoparticles with X-ray diffraction analysis. Antimicrobial activity against 10 different human pathogenic bacteria and fungi showed a broad spectrum inhibition against both Gram-positive and Gram-negative bacteria. Among the bacterial pathogens, B. Subtilis exhibited low activity compared to other pathogens. C. albicans was greatly controlled than other fungal species. A strong free radical scavenging activity of silver nanoparticles with IC50 values 31.29 ± 0.73, 19.83 ± 1.57, 35.64 ± 0.94, 42.07 ± 1.30, 29.70 ± 2.26, 29.10 ± 0.82, 36.80 ± 0.63 µg/ml was obtained in different antioxidant assays that were comparable to the reference. The study suggests that the silver nanoparticles can be biosynthesized from endophytic P. anthophila metabolites with significant therapeutic potential. With proper validation, the biosynthesized silver nanoparticles can be developed as a promising antiviral and anticancer drug candidate.

A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.

Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.

Self-organization Properties of a GPCR-Binding Peptide with a Fluorinated Tail Studied by Fluorine NMR Spectroscopy.

Conjugation of the bioactive apelin-17 peptide with a fluorocarbon chain results in self-organization of the peptide into micelles. Fluorine NMR spectroscopy studies show that the fluoropeptide's micelles are monodisperse, while proton NMR indicates that the peptide moiety remains largely disordered despite micellization. A very fast exchange rate is measured between the free and micellar states of the peptide which enables the number of molecules present in the micelle to be estimated as 200, in agreement with values found by dynamic light scattering measurements.

Studies on physiochemical modifications on biologically important hydroxyapatite materials and their characterization for medical applications.

Crystalline Hydroxyapatite (Ca10 (PO4)6(OH)2) non linear optical crystal plays a major role in biomedical applications. Crystalline Hydroxyapatite was synthesized using natural human bone sample by thermal methods. This Hydroxyapatite was characterized by Fourier Transform infra-red spectroscopy (FTIR), scanning electron microscope, UV-Vis spectroscopy, X-ray diffraction and conductivity studies. It was found that compared to bovine bone, the changes to the molecular structure associated with the mineral (carbonate) and the organic content (collagen) was good. The sintering methods showed that the synthesized Hydroxyapatite has remarkable heat stability up to 750 °C. The XRD and FTIR results showed a high purity of the synthesized HA powders, in terms of the electronic transitions, in UV-Vis which require a certain amount of energy it is proportional to the wavelength absorbed and absorption coefficient, the optical band energy of the natural human bone is found to be 4.65 eV and the electrical conductivity of the bone material is 9.11 × 10-6 Ω -1 cm-1. Natural bone Hydroxyapatite gives superior results.

Chemoselective Acylation of Hydrazinopeptides to Access Fluorescent Probes for Time-Resolved FRET Assays on GPCRs.

Fluorescence techniques represent a powerful tool to investigate dynamic and functional architecture of GPCRs. Thus, fluorescent GPCR ligands have found various applications in cellular imaging, in the development of binding assays as replacements for radioligands in the study of ligand-receptor but also in receptor-receptor interactions at the cell surface or in native tissues. To extend the applicability of these techniques, the design and the synthesis of fluorescent probes are critical steps. As there are numerous peptide receptors in the GPCR family, fluorescent peptide-based probes are of importance. Herein, we present a convenient method to facilitate the solution-phase fluorescent labeling of peptides which is based on the chemoselective acylation of α-hydrazinopeptides. This approach combines the advantages to use commercially available amine-reactive dyes and very mild conditions that are fully compatible with the chemical sensitivity of the dyes. It gives a rapid access to fluorescent peptidic probes compatible with the time-resolved fluorescence resonance energy transfer (TR-FRET) techniques.

Recurrent Diffuse Neurofibroma of Nose Associated with Neurofibromatosis Type 1: A Rare Case Report with Review of Literature.

Diffuse neurofibroma is an unusual variant of neurofibroma with the head and neck being the common sites of involvement. It is benign in nature and spreads superficially and has many ectatic blood vessels. Histologically it is similar to conventional neurofibromas except for a few peculiar distinguishing features. We report a case of a 14-year-old boy who presented with a diffuse recurrent painless swelling over the dorsum of the nose with the clinical stigmata of neurofibromatosis. Microscopy revealed a diagnosis of diffuse neurofibroma with a few foci showing differentiation towards Meissner's type of tactile corpuscles. It is important to recognize this entity as it has a tendency to recur, yet hardly ever become malignant and is almost always associated with neurofibromatosis type 1.

Tibia Fracture Healing Prediction Using First-Order Mathematical Model.

The prediction of healing period of a tibia fracture in humans across limb using first-order mathematical model is demonstrated. At present, fracture healing is diagnosed using X-rays. Recent studies have demonstrated electric stimulation as a diagnostic tool in fracture healing. A DC electric voltage of 0.7 V was applied across the fracture and stabilized with Teflon coated carbon rings and the data was recorded at different time intervals until the fracture heals. The experimental data fitted a first-order plus dead time zero model (FOPDTZ) that coincided with the mathematical model of electrical simulated tibia fracture limb. Fracture healing diagnosis was proposed using model parameter process gain. Current stabilization in terms of process gain parameter becoming constant indicates that the healing of fracture is a new finding in the work. An error analysis was performed and it was observed that the measured data correlated to the FOPDTZ model with an error of less than 2 percent. Prediction of fracture healing period was done by one of the identified model parameters, namely, process gain. Moreover, mathematically, it is justified that once the fracture is completely united there is no capacitance present across the fracture site, which is a novelty of the work.

Nodular Erythema Elevatum Diutinum Mimicking Kaposi's Sarcoma in a Human Immunodeficiency Virus Infected Patient.

Erythema elevatum diutinum (EED) has been emerging as a specific Human Immunodeficiency Virus (HIV) associated dermatosis in recent times. It is an extremely rare chronic disease of unknown origin and part of the spectrum of leukocytoclastic vasculitis. We describe a case of EED simulating Kaposi's sarcoma in a 52-year-old HIV infected female patient with no previous opportunistic infections and CD4+ count of 164/mm(3). Therapy with oral dapsone (100 mg/day) for two weeks resulted in resolution of some lesions.

A child with xeroderma pigmentosum for excision of basal cell carcinoma.

Xeroderma pigmentosum (XP) is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we are reporting a 9-year-old child with XP scheduled for excision of basal cell carcinoma under general anaesthesia.

Calcaneal chondrosarcoma: a case report.

Chondrosarcoma is a rare malignant cartilaginous tumour of the bone. It commonly occurs in the pelvis, scapula proximal femur, and shoulder girdle .We present a case of a woman in her 56 years of age with chondrosarcoma of the calcaneum-a rare lesion that accounts for 0.5-2.97% of all chondrosarcomas of other sites. Treatment for chondrosarcoma is generally wide surgical excision. Chemotherapy or radiation is not effective for most of these lesions.

Disseminated blastomycosis in a child with a brief review of the Indian literature.

Disseminated blastomycosis is rare in India, particularly in the pediatric population. We discuss the clinical picture, progress and outcome of disseminated blastomycosis in a 4-year-old child. We also present a brief review of the literature focussing on the scenario of blastomycosis in India.

Cervical epidural analgesia in a case of oral cancer undergoing reconstructive surgery.

We report a case of successful administration of cervical epidural analgesia in combination with general anaesthesia for a 50-year-old male patient of chronic obstructive pulmonary disease with carcinoma of tongue undergoing reconstructive surgery. Cervical epidural analgesia was provided with intermittent doses of 0.25% bupivacaine intraoperatively in addition to general anaesthesia and intermittent doses of 0.125% bupivacaine with tramodol 1 mg/kg postoperatively. It provides marked decrease in requirement of anaesthetic drugs, rapid recovery, reduced intensive care unit stay, and less pulmonary complications.

Multiple responses optimization and modeling of lipase production by Rhodotorula mucilaginosa MTCC-8737 using response surface methodology.

Response surface methodology was employed to optimize culture medium for production of lipase with Rhodotorula sp. MTCC 8737. In the first step, a Plackett-Burman design was used to evaluate the effects of different inducers qualitatively. Of all the seven inducers tested, soybean oil showed significant influence on the lipase production. Further, response surface studies were conducted to quantitatively optimize by considering linear, interactive, and quadratic effects of test variables. A novel approach was proposed to optimize the lipase production system by optimizing the responses in terms of yield kinetics rather than optimizing the direct responses like lipase titer and biomass growth. The coefficient of determination (R(2)) calculated for Y (P/S) (0.769), Y (P/X) (0.799), and Y (X/S) (0.847) indicated that the statistical model could explain 76.9%, 79.99%, and 84.7% of variability in the response.