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natural drugs

Bożena Małysiak-Mrozek
Understanding proteins, their structures, functions, mutual interactions, activity in cellular reactions, interactions with drugs, and expression in body cells is a key to efficient medical diagnosis, drug production, and treatment of patients. Machine learning and data exploration methods supported by many-valued logics allow to grasp the imprecision and uncertainties that naturally occur in proteins and other biomolecules. Many-valued logics, like Łukasiewicz logic or fuzzy logic, are non-classical logics that do not restrict the number of truth values to only two values of true or false, but they allow for a larger set of truth degrees...
August 10, 2018: Mathematical Biosciences
Qianwen Wang, Zhong Zuo
In parallel with the blood-brain barrier (BBB), transporters and enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first barrier for drug brain uptake. In addition, their expressions on the brain parenchyma are considered as the secondary barrier for central nervous system (CNS) drug delivery. Currently, a lack of information on transporters and enzymes expressed on both BCSFB and brain parenchyma is the major cause of failure in CNS drug development. Areas covered: Transporters and enzymes expressed on BCSFB as well as brain parenchyma and their impact on drug brain uptake was highlighted and compared with that on BBB...
August 17, 2018: Expert Opinion on Drug Metabolism & Toxicology
Cole Vonder Haar, Jacqueline-Marie N Ferland, Sukhbir Kaur, Lara-Kirstie Riparip, Susanna Rosi, Catharine A Winstanley
Traumatic brain injury (TBI) has been linked to the development of numerous psychiatric diseases, including substance use disorder. However, it can be difficult to ascertain from clinical data whether the TBI is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which TBI could magnify the risk of substance dependence, numerous studies indicate that TBI can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation...
August 17, 2018: European Journal of Neuroscience
Gabriel Silva, Mozart Marins, Nadda Chaichanasak, Yongdae Yoon, Ana Lúcia Fachin, Vitor Caressato Pinhanelli, Luis Octávio Regasini, Mariana Bastos Dos Santos, Gabriela Miranda Ayusso, Beatriz de Carvalho Marques, Wells W Wu, Je-Nie Phue, Rong-Fong Shen, Seung Joon Baek
Naturally-occurring chalcones and synthetic chalcone analogues have been demonstrated to have many biological effects, including anti-inflammatory, anti-malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer cell growth as shown via in vitro assays, and exerts anti-cancerous effects via the activation of the p53 tumor suppressor protein. Thus, characterization of the specific mechanisms, by which trans-chalcone activates p53, can aid development of new chemotherapeutic drugs that can be used individually or synergistically with other drugs...
2018: PloS One
Shaheer Maher, Tushar Kumeria, Moom Sin Aw, Dusan Losic
Diatoms are unicellular photosynthetic algae enclosed in porous 3D nanopatterned silica enclosures called "frustules." The diatom frustules are made from biosilica self-assembled into intricate porous shells that feature unique properties including high specific surface area, biocompatibility, tailorable surface chemistry, thermal stability, and high mechanical and chemical resistance. The ability to cultivate diatoms in artificial environments and their abundant availability of diatom frustules as mineable fossilized mineral deposits (diatomite or diatomaceous earth; DE) make diatom silica a promising natural alternative to synthetic porous silica for a broad range of biomedical, environmental, agricultural, and energy applications...
August 17, 2018: Advanced Healthcare Materials
Erin V McConnell, Igor Bruzual, Sovitj Pou, Rolf W Winter, Rozalia A Dodean, Martin J Smilkstein, Alina Krollenbrock, Aaron Nilsen, Lev N Zakharov, Michael K Riscoe, J Stone Doggett
Cytochrome bc1 inhibitors have been broadly studied as human and veterinary medicines, and agricultural fungicides. For the most part, cytochrome bc1 inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with ubiquinone at the quinone reduction (Qi ) site. 4(1H)-quinolones with 3-position substituents may inhibit either site based on quinolone ring substituents. 4(1 H)-quinolones that inhibit the Qi site are highly effective against toxoplasmosis, malaria and babesiosis and do not inhibit human cytochrome bc1 ...
August 17, 2018: ACS Infectious Diseases
Ankit Parikh, Krishna Kathawala, Jintao Li, Chi Chen, Zhengnan Shan, Xia Cao, Xin-Fu Zhou, Sanjay Garg
Curcumin (CUR), a natural polyphenolic compound, is considered as one of the most potential candidates against Alzheimer disease (AD) by targeting multiple pathologies such as amyloid-beta, tau phosphorylation, and oxidative stress. Poor physicochemical profile and oral bioavailability (BA) are the major contributors to its failure in clinical trials. Lack of success in numerous drug clinical trials for the treatment of AD urges the need of repositioning of CUR. To overcome its limitation and enhance oral BA, Novel CUR Formulation (NCF) was developed using self-nanomicellizing solid dispersion strategy which displayed 117-fold enhancement in oral BA of CUR...
August 16, 2018: Drug Delivery and Translational Research
Dorota Wróblewska, Monika Rudkowska, Monika Banach, Kinga K Borowicz-Reutt
The aim of the study was to evaluate precisely the type of interactions between mexiletine (an antiarrhythmic drug) and four new generation antiepileptic drugs: lamotrigine, oxcarbazepine, topiramate and pregabalin in the maximal electroshock test in mice (MES). The isobolographic analysis was used to assess the nature of interactions between the tested drugs. Total brain concentrations of antiepileptics were also measured to detect possible pharmacokinetic interactions. The results obtained indicated that the mixture of mexiletine and pregabalin at the fixed ratios of 1:1 and 3:1 led to supra-additive interaction in terms of seizure suppression, while the proportion of 1:3 occurred additive...
August 16, 2018: Neurochemical Research
Madeline Rodríguez-Valentín, Sheila López, Mariela Rivera, Eddy Ríos-Olivares, Luis Cubano, Nawal M Boukli
Aim: Intense interest remains in the identification of compounds to reduce human immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor 's polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory properties with the ability to activate an innate immune response through Toll-like receptor 4 (TLR4) showing insignificant toxicity. This study sought to determine the potential use of PSP as an anti-HIV agent and whether its antiviral immune response was TLR4 dependent...
2018: Journal of Immunology Research
Lei Li, Qing Wu, Xi Wang, Huimin Lu, Xinping Xi, Mei Zhou, Chris J Watson, Tianbao Chen, Lei Wang
Abundant biologically active peptides have been discovered from frog skin secretions, a rich natural source of bioactive compounds with great potential in drug discovery. In this study, three Caeridin peptides, namely, Caeridin-1, S5-Caeridin-1, and Caeridin-a1, were discovered from the skin secretion of the Australian White's tree frog, Litoria caerulea , for the first time, by means of combining transcriptomic and peptidomic analyses. It also represents the first report on bioactive Caeridins since this family of peptides was initially studied 20 years ago...
2018: International Journal of Genomics
Austin B Henslee, Timothy A Steele
Background: Aggressive natural killer cell leukemia is a devastating disease, with an average patient survival time of less than 2 months following diagnosis. Due to P-glycoprotein-mediated resistance of the tumor cells most forms of chemotherapy are of limited efficacy, therefore new treatment strategies are needed. Statin drugs have recently been found to inhibit the growth of various tumor cell types. Methods: We investigated the effects of statin drug-mediated mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity, cell cycle progression and ERK MAP kinase signal transduction pathway activation...
2018: Biomarker Research
Mohammad Tuhin Ali, Natalia Blicharska, Jamil A Shilpi, Veronique Seidel
Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading bacterial killer disease worldwide and new anti-TB drugs are urgently needed. Natural remedies have long played an important role in medicine and continue to provide some inspiring templates for drug design. Propolis, a substance naturally-produced by bees upon collection of plant resins, is used in folk medicine for its beneficial anti-TB activity. In this study, we used a molecular docking approach to investigate the interactions between selected propolis constituents and four 'druggable' proteins involved in vital physiological functions in M...
August 16, 2018: Scientific Reports
Dainis Kaldre, Immo Klose, Nuno Maulide
The chemistry of the carbonyl group is essential to modern organic synthesis. The preparation of substituted, enantioenriched 1,3- or 1,5-dicarbonyls is well developed, as their disconnection naturally follows from the intrinsic polarity of the carbonyl group. By contrast, a general enantioselective access to quaternary stereocenters in acyclic 1,4-dicarbonyl systems remains an unresolved problem, despite the tremendous importance of 2,3-substituted 1,4-dicarbonyl motifs in natural products and drug scaffolds...
August 17, 2018: Science
Shyam Sundhar Bale, Jeffrey T Borenstein
Animal models such as rats and primates provide body-wide information for drug and metabolite responses, including organ-specific toxicity and any unforeseen side effects on other organs. While effective in the drug screening process, their translatability to humans is limited due to the lack of high concordance and correlation between enzymatic mechanisms, cellular mechanisms and resulting toxicities. A significant mode of failure for safety prediction in drug screening is hepatotoxicity, resulting in ~30% of all safety-related drug failures and withdrawals from the market...
August 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
J DeCamilla, X Xia, M Wang, J Wade, B Mykins, W Zareba, J P Couderc
The convergence between wearable and medical device technologies is a natural progression. Miniaturization has allowed the design of small, compact monitoring systems that can record physiological signals over longer periods of time. Thus, the potential for these devices to expand the understanding of disease progression and patients' clinical status is very high. The accuracy of these devices, however, is dependent upon the computer algorithms utilized in the analysis of the large volume of physiological data monitored and/or recorded by the devices...
August 9, 2018: Journal of Electrocardiology
Andrea Matucci, Alessandra Vultaggio, Romano Danesi
BACKGROUND: Monoclonal antibodies (mAbs) approved for use as add-on therapy in patients with severe asthma target the underlying pathogenesis of asthma. MAIN BODY: Omalizumab binds immunoglobulin E (IgE), thereby inhibiting its interaction with the high-affinity IgE receptor and reducing the quantity of free IgE available to trigger the allergic cascade. Anti-interleukin (IL)-5 mAbs mepolizumab, benralizumab and reslizumab block the interaction between IL-5 and its receptor on eosinophils, thus targeting the eosinophilic pathway in asthma...
August 16, 2018: Respiratory Research
Jaykant Vora, Shivani Patel, Sonam Sinha, Sonal Sharma, Anshu Srivastava, Mahesh Chhabria, Neeta Shrivastava
The transmission of mosquito-borne Chikungunya virus (CHIKV) has large epidemics worldwide. Till date, there are neither anti-viral drugs nor vaccines available for the treatment of Chikungunya. Accumulated evidences suggest that some natural compounds i.e. Epigallocatechin gallate, Harringtonine, Apigenin, Chrysin, Silybin etc. have the capability to inhibit CHIKV replication in vitro. Natural compounds are known to possess less or no side effects. Therefore, natural compound in its purified or crude extracts form could be the preeminent and safe mode of therapies for Chikungunya...
August 16, 2018: Journal of Biomolecular Structure & Dynamics
Daniela Loessner, Peter Goettig, Sarah Preis, Johanna Felber, Holger Bronger, Judith A Clements, Julia Dorn, Viktor Magdolen
Aberrant levels of kallikrein-related peptidases (KLK1-15) have been linked to cancer cell proliferation, invasion and metastasis. In ovarian cancer, the KLK proteolytic network has a crucial role in the tissue and tumor microenvironment. Publically available ovarian cancer genome and expression data from multiple patient cohorts show an upregulation of most KLKs. Areas covered: Here, we review the expression levels of all 15 members of this family in normal and ovarian cancer tissues, categorizing them into highly and moderately or weakly expressed KLKs, and their association with patient prognosis and survival...
August 17, 2018: Expert Opinion on Therapeutic Targets
Antonella Frattari, Ennio Polilli, Vanessa Primiterra, Vincenzo Savini, Tamara Ursini, Giancarlo Di Iorio, Giustino Parruti
A better knowledge of factors predicting the development of sepsis in patients hospitalized in intensive care unit (ICU) might help deploy more targeted preventive and therapeutic strategies. In addition to the known clinical and demographic predictors of septic syndromes, in this study, we investigated whether measuring T and B lymphocyte subsets upon admission in the ICU may help individualize the prediction of ensuing sepsis during ICU stay. Between May 2015 and December 2016, we performed a prospective cohort study evaluating peripheral blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 + (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on blood samples collected 2 days after admission in the ICU...
January 2018: International Journal of Immunopathology and Pharmacology
Dun Liu, Hao Zhang, Yuquan Wei, Bo Liu, Yipeng Lin, Guanghe Li, Fang Zhang
Fenton based reactions are effective for pharmaceutical removals, but traditional Fenton processes have drawbacks of pH adjustment and large amount of produced iron sludge. To overcome these challenges, a heterogeneous electro-Fenton process was proposed for effective contaminant degradation at circumneutral pH without iron sludge production. The anti-inflammatory drug ibuprofen (a common pharmaceutical in natural waters) was used as a representative contaminant. Activated carbon fibers (ACFs) supported ferric citrate (Cit-Fe/ACFs) was synthesized and used as the cathode, and RuO2 /Ti was used as the anode...
October 2018: Chemosphere
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