THERAPEUTIC POTENTIAL OF CICHORIUM INTYBUS IN LIFESTYLE DISORDERS: A REVIEW

ABSTRACTThe genus Cichorium (Asteraceae) is comprised six species, widely cultivated in Europe and Asia. Cichorium intybus (common name- chicory) isused as a coffee substitute. However, its leaves, flowers, seeds, and roots have been customarily utilized as home grown solution for various ailmentssince ancient times. Although commercialized as coffee substitute, C. intybus is also used in indigenous system of medicine to treat different ailmentsfrom wounds to diabetes. Several numbers of chemical constituents of chicory have been identified, and a significant number of these constituentshave not been fully investigated for their pharmacological potential. Toxicological information on chicory is also limited. This review targets on thesocially imperative medicinal use of chicory in lifestyle disorders. The pharmacological activities of this plant in lifestyle disorders, phytochemicalcomposition (active compounds) isolated from chicory plant with medicinal importance and safety studies are discussed in detail.Keywords: Cichorium intybus, Insulin resistance, Chicory extract, Non-alcoholic fatty liver disease

Identification of Putative Vero Cell Protein(s) that Bind Specifically to Recombinant Envelope Protein of Dengue Virus Type 2

Purpose: To identify protein targets in host (vero) cell since there is currently no therapy or a licensed tetravalent vaccine to combat all the four virus serotypes of dengue virus.Methods: The domain III of the dengue virus encoded envelope protein was expressed in pET28a expression vector and the purified recombinant protein was labeled with biotin without altering its immunogenicity. Vero cell proteins on nitrocellulose membrane reacted with recombinant envelope protein domain III to identify viral target proteins in vero cells.Results: The 45 KDa, 43 KDa and 30 KDa plasma membrane proteins were identified as viral envelope targets. Competitive binding assay showed these proteins competing with dengue virus binding. MTT assay indicate that viability of vero cells increases in cultures pretreated with 45 KDa, 43 KDa and 30 KDa proteins before dengue infection.Conclusion: These results indicate the possible role of these proteins in viral binding to vero cells. The study provides a preliminary insight that would aid in determining the target epitopes against protein E domain III of dengue virus and hence, formulation of a vaccine for preparing neutralizing antibodies.Keywords: Dengue virus envelope, Biotinylation, Ni-NTA purification, Target epitopes, Plaque assay, Competitive blocking assa

Flurbiprofen- and Suprofen-Dextran Conjugates: Synthesis, Characterization and Biological Evaluation

Purpose: To synthesize and characterize the dextran conjugates of suprofen and flurbiprofen, and also evaluate their biological activities.Methods: Suprofen and flurbiprofen were individually reacted with carbonyldiimidazole to form acylimidazole, which, in turn, was reacted with the dextran of varying molecular weight (40 000, 60 000, and 110 000) to form drug-dextran conjugates. The structures of the synthesized dextran conjugates were confirmed by IR and NMR spectroscopy. In vitro hydrolysis of the conjugates were studied in buffer solutions (pH 7.4 and 9.0) and 80% human plasma (pH 7.4). The analgesic and antipyretic activities, aswell as the ulcerogenic index of the conjugates were also evaluated in albino rats.Results: The mean degree of substitution of flurbiprofen and suprofen was between 8.0 to 9.5 % and 7.5 to 9.0 %, respectively. In vitro hydrolysis studies on the conjugates indicate faster hydrolysis at pH9.0 than in pH 7.4 buffer solution and 80% human plasma (pH 7.4) with the process following First order kinetics. The analgesic activity of flurbiprofen-dextran conjugate (FD-110) suprofen-dextran conjugate(SD-110) was 64.23 and 41.50% which compare well with those of their parent drugs - flurbiprofen (72.60%) and suprofen (44.30%). Similar findings were made in respect of the antipyretic activity. Bothflurbiprofen and suprofen showed deep ulceration, swelling and high intensity perforation in the gastric mucosa after seven days administration of flurbiprofen and suprofen with the ulcerogenic indices of29.69 and 31.0 respectively, cpmpare with 5.88 and 6.06 for FD-110 and SD-110, respectively.Conclusion: Dextran can be employed as a pro-moiety or carrier for the delivery of flurbiprofen and suprofen and showed comparable analgesic and antipyretic activities with the parent drugs but with lower ulcerogenic indices

Study of Epalrestat in Diabetic Distal Symmetric Polyneuropathy and correlation of its therapeutic efficacy with erythrocyte sorbitol levels : A step towards Precision Medicine

Aims : Diabetic Distal Symmetric Polyneuropathy (DSPN), despite being the most common and a disabling diabetic complication, remains difficult to treat. It has led to rekindle our interest in Epalrestat which has the potential to alter the natural history of the disease. The present study was designed to evaluate the efficacy of Epalrestat in DSPN and to corelate its therapeutic efficacy with baseline erythrocyte sorbitol levels. Methods : 100 patients with duration of diabetes more than five years and Diabetic Neuropathy Symptom Score (DNSS) ≥ 1 were included. They were divided into two groups of 50 patients each : Group 1 (received Tablet Epalrestat 150 mg once a day), Group 2 (received placebo). Baseline Diabetic Neuropathy Symptom Score (score out of 4), Numeric Pain Intensity Scale (score out of 10), Monofilament score (score out of 10), Vibration Perception Threshold (VPT) by Sensitometer and erthyrocyte sorbitol levels (by ELISA) were recorded. Same parameters were repeated at three months follow up visit. Results : Epalrestat was overall more effective than placebo in improving the symptoms as well as in improving the quantitative sensory nerve function measured by sensitometer The improvement in all the parameters positively correlated with baseline erythrocyte sorbitol levels. Conclusions : Epalrestat offers a ray of hope in the treatment of DSPN patients who have high baseline erythrocyte sorbitol levels and thus can be a useful tool in predicting the response to drug

Effects of stitching on delamination of satin weave carbon-epoxy laminates under mode I, mode II and mixed-mode I/II loadings

The objective of the present study is to characterize the effect of modified chain stitching on the delamination growth under mixed-mode I/II loading conditions. Delamination toughness under mode I is experimentally determined, for unstitched and stitched laminates, by using untabbed and tabbed double cantilever beam (TDCB) tests. The effect of the reinforcing tabs on mode I toughness is investigated. Stitching improves the energy release rate (ERR) up to 4 times in mode I. Mode II delamination toughness is evaluated in end-notched flexure (ENF) tests. Different geometries of stitched specimens are tested. Crack propagation occurs without any failure of stitching yarns. The final crack length attains the mid-span or it stops before and the specimen breaks in bending. The ERR is initially low and gradually increases with crack length to very high values. The mixedmode delamination behaviour is investigated using a mixed-mode bending (MMB) test. For unstitched specimens, a simple mixed-mode criterion is identified. For stitched specimens, stitching yarns do not break during 25% of mode I ratio tests and the ERR increase is relatively small compared to unstitched values. For 70% and 50% of mode I ratios, failures of yarns are observed during crack propagation and tests are able to capture correctly the effect of the stitching: it clearly improves the ERR for these two mixed modes, as much as threefold

Efficacy of anti-thrombotic treatment in thrombophilia patients with adverse pregnancy outcome

Background: Thrombophilia is a potentially treatable cause of adverse pregnancy outcome. The objective was to compare the fetomaternal outcome in thrombophilia patients with adverse pregnancy outcome after treating with low-molecular-weight (LMW)/ unfractionated heparin and aspirin.Methods: 54 antenatal women studied who had an earlier or presenting pregnancy complicated by adverse pregnancy outcome were included in this study. In the present pregnancy, therapy consisting of LMW heparin and aspirin was administered who were found to be thrombophilia positive. Patients also received folic acid supplementation throughout their pregnancy. The fetomaternal outcome is compared according to the time of initiation of treatment.Results: Low-molecular-weight heparin and aspirin was well tolerated and none of the women or the newborns developed any hemorrhagic complications.3 thrombophilia negative cases with history of recurrent pregnancy loss aborted even getting treatment from 1 trimester. 1 thrombophilia positive case with history of recurrent pregnancy loss aborted when received treatment from 2nd trimester. There is 25.8% increase in birth weight of neonate if thrombophilia positive cases were treated from 1st trimester. Whereas there was only 10.23% increase in birth weight in thrombophilia negative cases when treated from first trimester. We found, our treatment was significantly effective in preventing IUD, IUGR, abruption, abortion, eclampsia. Though prevention of PIH had no significant correlation with antithrombotic treatment, only 2 cases booked from 1st trimester developed PIH among thrombophilia positive cases. But neither of cases had suffered from any severe complication as compared to 81% of eclampsia cases, 16.67% of DVT cases, 1 case of mortality in cases treated after third trimester.Conclusions: This case control trial suggests that patients with adverse pregnancy outcome and thrombophilia may get benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. We suggest all patients with adverse pregnancy outcome should be investigated for thrombophilia markers

Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite <it>Plasmodium falciparum </it>contains two nucleosome assembly proteins termed PfNapL and PfNapS.</p> <p>Methods</p> <p>Three-dimensional crystal structure of PfNapS has been determined and analysed. Gene knockout and localization studies were also performed on PfNapS using transfection studies. Fluorescence spectroscopy was performed to identify histone-binding sites on PfNapS. Extensive sequence and structural comparisons were done with the crystal structures available for NAP/SET family of proteins.</p> <p>Results</p> <p>Crystal structure of PfNapS shares structural similarity with previous structures from NAP/SET family. Failed attempts to knock-out the gene for PfNapS from malaria parasite suggest essentiality in the parasite. GFP-fused PfNapS fusion protein targeting indicates cellular localization of PfNapS in the parasite nucleus. Fluorescence spectroscopy data suggest that PfNapS interacts with core histones (tetramer, octamer, H3, H4, H2A and H2B) at a different site from its interaction with linker histone H1. This analysis illustrates two regions on the PfNapS dimer as the possible sites for histone recognition.</p> <p>Conclusions</p> <p>This work presents a thorough analysis of the structural, functional and regulatory attributes of PfNapS from <it>P. falciparum </it>with respect to previously studied histone chaperones.</p

Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities