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The science of cars
by
Heiman, Larry, 1949- author
,
Disney Storybook Artists, illustrator
in
Cars 3 (Motion picture) Juvenile literature.
,
Cars 3 (Motion picture)
,
Automobiles Juvenile literature.
2019
\"Lightning McQueen, Doc Hudson, Smoky and others explore the science of cars. From how a car works to Formula One racing, clear, nonfiction text give all the details\"-- Provided by publisher.
Synthesis and Biological Evaluation of Thalidomide Derivatives as Potential Anti-Psoriasis Agents
by
Fang, Jia-You
,
Tang, Kai-Wei
,
Lin, Zih-Chan
in
anti-inflammatory
,
Anti-Inflammatory Agents - chemical synthesis
,
Anti-Inflammatory Agents - pharmacology
2018
Several thalidomide derivatives were synthesized and evaluated for their anti-inflammatory activity. Introduction of the benzyl group to the parent thalidomide is unfavorable in which 2-(1-benzyl-2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (
) was inactivated. However, the inhibitory activities on TNF-α and IL-6 expression in HaCaT cells were improved by the substitution of a chloro- or methoxy- group at the phenyl position of
. The IL-6 inhibitory activity decreased in an order of
(69.44%) >
(48.73%) >
(3.19%) indicating the 3-substituted derivative is more active than the 4-substituted counterpart, which in turn is more active than the 2-substituted counterpart. Among them, 2-[1-(3-chlorobenzyl)-2,6-dioxopiperidin-3-yl]isoindoline-1,3-dione (
) was found to inhibit TNF-α and IL-6 expression in HaCaT cells with a higher potency than thalidomide and no significant cell cytotoxicity was detected at 10 μM. In psoriasis, Compound
reduced IL-6, IL-8, IL-1β and IL-24 in imiquimod-stimulated models. Our results indicated that compound
is a potential lead of novel anti-psoriasis agents. Structural optimization of compound
and its in vivo assay are ongoing.
Journal Article
Synthesis and characterization of 1,2,4-triazole containing hydrazide-hydrazones derived from (S)-naproxen as anticancer agents
A novel series of new naproxen derivatives (S)-ethyl{[4-(4-fluorophenyl)-5-[(1-(6-methoxynaphtalen-2-yl)ethyl)]-4H-1,2,4-triazole-3-yl]sulphanyl}acetate (5), (S)-2-({5-[1-(6-methoxynaphtalen-1-yl)ethyl]-4-fluorophenyl-4H-1,2,4-triazole-3-yl}sulphanyl)acetohydrazide (6), 2-{[5-[1-(6-methoxynaphtalen-2-yl)ethyl]-4-(4-fluorophenyl)-4H-1,2,4-triazole-3-yl]sulphanyl}-N'-[(substituted)methylidene]acetohydrazides (7a-m) were synthesized, in this study. The structures of compounds 5, 6 and 7a-m were defined by spectral (1H-NMR, 13C-NMR, HR-MS and FT-IR) methods and their purity was proven by elemental analysis, thin layer chromatography and high pressure liquid chromatography. These compounds were evaluated for in vitro anticancer activity by using MTS method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. Compounds (7a-m) exhibited anticancer activity with IC50 values of 87.2-400 μM against prostate cancer cell lines.
Journal Article
من تاريخ الصين : التحولات السياسية والفكرية في الصين (771-221 ق. م)
by
عجيل، ناصر رحيم مؤلف
,
سمار، سعد عبود مراجع
in
الصين تاريخ قرون 8-3 قبل الميلاد
,
الصين سياسة وحكومة تاريخ قرون 8-3 قبل الميلاد
,
الصين حياة فكرية تاريخ قرون 8-3 قبل الميلاد
2022
يتناول هذا الكتاب عدة محاور منها أصول تسمية الصين وجغرافية الصين وأثرها السكاني: أصل السكان واللغة الصينية ونشأة الكتابة والبنية السياسية والفكرية للصين في عهد سلالة تشو حتى عام النكبة 771 ق. م) والتحولات السياسية بعد استيلاء سلالة تشو على السلطة وغزو تشو وأزمة سقوط شانغ ونكبة عام 771 ق. م وسقوط عاصمة تشو الغربية والعوامل الخارجية وهجمات البرابرة والبنية السياسية وأسس الحكم في الصين القديمة وتطورها ونشوء النظام السياسي وتطوره: ومنها مبدأ التفويض السماوي واختيار السماء لحكام تشو والإقطاع في عهد سلالة تشو والبنية الفكرية في الصين القديمة قبل كونفوشيوس والفكر الصيني وتطوره، وأساطير الخلق والآلهة في الصين القديمة، والآلهة – السماء والعناصر الخمسة وفرضية الين ولليانغ ، وصعود كين وعمليات توحيد الصين والصراعات الفكرية في ظل الانقسامات السياسية للدويلات المتحاربة والمدرسة القانونية ونتاجها الفكري.
Transient receptor potential channels: targeting pain at the source
by
Patapoutian, Ardem
,
Tate, Simon
,
Woolf, Clifford J
in
Analgesics - therapeutic use
,
Animals
,
Drug therapy
2009
Pain results from the complex processing of neural signals at different levels of the central nervous system, with each signal potentially offering multiple opportunities for pharmacological intervention. A logical strategy for developing novel analgesics is to target the beginning of the pain pathway, and aim potential treatments directly at the nociceptors--the high-threshold primary sensory neurons that detect noxious stimuli. The largest group of receptors that function as noxious stimuli detectors in nociceptors is the transient receptor potential (TRP) channel family. This Review highlights evidence supporting particular TRP channels as targets for analgesics, indicates the likely efficacy profiles of TRP-channel-acting drugs, and discusses the development pathways needed to test candidates as analgesics in humans.
Journal Article
حمية الأوميغا 3 و6 و9، أو، العلاج والوقاية بالرجيم الغذائي الحديث : أمراض القلب-البدانة-إلتهاب المفاصل-تخثر الدم-مشاكل الجلد والبشرة-أمراض الجهاز البولي-الربو والأمراض التنفسية-الإكتئاب ومشاكل الجهاز العصبي-الأمراض النسائية-ضغط الدم العالي-الكوليسترل وثلاثي الترايغليسيريد-السكتى الدماغية-أمراض الأوعية الدموية-أمراض الجهاز الهضمي-أمراض البروستات-الذاكرة-السكري ومشاكل الغدة الدرقية-السرطان
by
جعفر، غسان، 1962- مؤلف
in
الرجيم جوانب صحية
,
الأحماض الدهنية أوميجا-3 جوانب صحية
,
الأغذية والصحة
2000
Ionotropic and metabotropic glutamate receptor structure and pharmacology
2005
L: -Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS) and mediates its actions via activation of both ionotropic and metabotropic receptor families. The development of selective ligands, including competitive agonists and antagonists and positive and negative allosteric modulators, has enabled investigation of the functional roles of glutamate receptor family members.
In this review we describe the subunit structure and composition of the ionotropic and metabotropic glutamate receptors and discuss their pharmacology, particularly with respect to selective tools useful for investigation of their function in the CNS.
A large number of ligands are now available that are selective either for glutamate receptor subfamilies or for particular receptor subtypes. Such ligands have enabled considerable advances in the elucidation of the physiological and pathophysiological roles of receptor family members. Furthermore, efficacy in animal models of neurological and psychiatric disorders has supported the progression of several glutamatergic ligands into clinical studies. These include ionotropic glutamate receptor antagonists, which have entered clinical trials for disorders including epilepsy and ischaemic stroke, alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor positive allosteric modulators which are under evaluation as cognitive enhancers, and metabotropic glutamate receptor 2 (mGluR2) agonists which are undergoing clinical evaluation as anxiolytics. Furthermore, preclinical studies have illustrated therapeutic potential for ligands selective for other receptor subtypes in various disorders. These include mGluR1 antagonists in pain, mGluR5 antagonists in anxiety, pain and drug abuse and mGluR5 positive allosteric modulators in schizophrenia.
Selective pharmacological tools have enabled the study of glutamate receptors. However, pharmacological coverage of the family is incomplete and considerable scope remains for the development of novel ligands, particularly those with in vivo utility, and for the their use together with existing tools for the further investigation of the roles of receptor family members in CNS function and as potentially novel therapeutics.
Journal Article
Emerging Importance of Survivin in Stem Cells and Cancer: the Development of New Cancer Therapeutics
by
Warrier, Neerada Meenakshi
,
Kumar, Praveen
,
Agarwal Prasoon
in
Cancer
,
Clinical trials
,
Drug development
2020
Survivin is one of the rare proteins that is differentially expressed in normal and cancer cells and is directly or indirectly involved in numerous pathways required for tumor maintenance. It is expressed in almost all cancers and its expression has been detected at early stages of cancer. These traits make survivin an exceptionally attractive target for cancer therapeutics. Even with these promising features to be an oncotherapeutic target, there has been limited success in the clinical trials targeting survivin. Only recently it has emerged that survivin was not being specifically targeted which could have resulted in the negative clinical outcome. Also, focus of research has now shifted from survivin expression in the overall heterogeneous tumor cell populations to survivin expression in cancer stem cells as these cells have proved to be the major drivers of tumors. Therefore, in this review we have analyzed the expression of survivin in normal and cancer cells with a particular focus on its expression in cancer stem cell compartment. We have discussed the major signaling pathways involved in regulation of survivin. We have explored the current development status of various types of interventions for inhibition of survivin. Furthermore, we have discussed the challenges involving the development of potent and specific survivin inhibitors for cancer therapeutics. Finally we have given insights for some of the promising future anticancer treatments.
Journal Article