The Use of Seahorse Extracellular Flux Analyzer in Mechanistic Studies of Naturally Occurring Cancer Chemopreventive Agents

Author(s):  
Michelle B. Moura ◽  
Eun-Ryeong Hahm ◽  
Bennett Van Houten ◽  
Shivendra V. Singh
Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2316 ◽  
Author(s):  
Qiuchen Zheng ◽  
Micheal T. Kebede ◽  
Merc M. Kemeh ◽  
Saadman Islam ◽  
Bethany Lee ◽  
...  

The amyloid-β (Aβ) peptide and tau protein are thought to play key neuropathogenic roles in Alzheimer’s disease (AD). Both Aβ and tau self-assemble to form the two major pathological hallmarks of AD: amyloid plaques and neurofibrillary tangles, respectively. In this review, we show that naturally occurring polyphenols abundant in fruits, vegetables, red wine, and tea possess the ability to target pathways associated with the formation of assemblies of Aβ and tau. Polyphenols modulate the enzymatic processing of the amyloid-β precursor protein and inhibit toxic Aβ oligomerization by enhancing the clearance of Aβ42 monomer, modulating monomer–monomer interactions and remodeling oligomers to non-toxic forms. Additionally, polyphenols modulate tau hyperphosphorylation and inhibit tau β-sheet formation. The anti-Aβ-self-assembly and anti-tau-self-assembly effects of polyphenols increase their potential as preventive or therapeutic agents against AD, a complex disease that involves many pathological mechanisms.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yali Zhou ◽  
Xingjun Xu ◽  
Hongwei Sun ◽  
Guanyu Tao ◽  
Xiao-Yong Chang ◽  
...  

AbstractHydrofunctionalization, the direct addition of an X–H (e.g., X=O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of “donor–acceptor”-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns are accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound “donor–acceptor”-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.


2020 ◽  
Author(s):  
Yali Zhou ◽  
Xingjun Xu ◽  
Hongwei Sun ◽  
Guanyu Tao ◽  
Xiaoyong Chang ◽  
...  

Abstract Hydrofunctionalization, the direct additon of an X–H (e.g., X = O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of “donor–acceptor”-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns were accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound “donor–acceptor”-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.


2019 ◽  
Vol 23 (12) ◽  
pp. 1307-1341 ◽  
Author(s):  
Zulfa Nooreen ◽  
Sudeep Tandon ◽  
Narayan P. Yadav ◽  
Prabhat Kumar ◽  
Tran D. Xuan ◽  
...  

Zanthoxylum, commonly known as Timoor, has been used in different traditional systems of medicine and also for several other applications such as chemopreventive agents, tooth care, as spices, condiments, etc. Due to the pungent taste of fruits, seeds, leaves, bark, and therapeutic remedies, especially in Indian system of medicine, Eastern Asian countries and in Central America, it is being substituted for pepper. The collection of Zanthoxylum armatum DC; Syn. Z. alatum Roxb and its several species used for food, medicine and barter has been a part of the culture of many communities in different countries. The fruits and seeds of timoor are well known in ayurvedic medicine and used for different diseases. The bark of the plant has also been reported for hepatoprotective activity. Several natural compounds have been isolated and identified in several classes, from different plant parts and species. The Zanthoxylum compounds and extracts of the plant parts have been reported for several types of biological activities. This review aims to examine the detailed aspects of phytochemical compounds and pharmacological activities covering maximum species of this genus. In view of the available pharmacological data and traditional use in Indian system of medicine and in other countries also, Z. armatum and other species certainly deserve more investigations. However, clinical evidence and rigorous investigations for quality control are required before any recommendation for Zanthoxylum based products.


2021 ◽  
Vol 22 (18) ◽  
pp. 9707
Author(s):  
Teodora Daria Pop ◽  
Zorita Diaconeasa

Skin cancer represents any tumor development from the cutaneous structures within the epidermis, dermis or subcutaneous tissue, and is considered to be the most prevalent type of cancer. Compared to other types of cancer, skin cancer is proven to have a positive growth rate of prevalence and mortality. There are available various treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, but because of the multidrug resistance development, a low success has been registered. By this, the importance of studying naturally occurring compounds that are both safe and effective in the chemoprevention of skin cancer is emphasized. This review focuses on melanoma because it is the deadliest form of skin cancer, with a significantly increasing incidence in the last decades. As chemopreventive agents, we present polyphenols and their antioxidant activity, anti-inflammatory effect, their ability to balance the cell cycle and to induce apoptosis and their various other effects on skin melanoma. Besides chemoprevention, studies suggest that polyphenols can have treating abilities in some conditions. The limitations of using polyphenols are also pointed out, which are related to their poor bioavailability and stability, but as the technology is well developed, it is possible to augment the efficacy of polyphenols in the case of melanoma.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1474
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos

Type 2 diabetes (T2D) and obesity are relevant worldwide chronic diseases. A common complication in both pathologies is the dysregulation of the insulin-signaling pathway that is crucial to maintain an accurate glucose homeostasis. Flavonoids are naturally occurring phenolic compounds abundant in fruits, vegetables and seeds. Rising evidence supports a role for the flavonoids against T2D and obesity, and at present, these compounds are considered as important potential chemopreventive agents. This review summarizes in vitro and in vivo studies providing data related to the effects of flavonoids and flavonoid-rich foods on the modulation of the insulin route during T2D and obesity. Notably, few human studies have evaluated the regulatory effect of these phenolic compounds at molecular level on the insulin pathway. In this context, it is also important to note that the mechanism of action for the flavonoids is not fully characterized and that a proper dosage to obtain a beneficial effect on health has not been defined yet. Further investigations will contribute to solve all these critical challenges and will enable the use of flavonoids to prevent, delay or support the treatment of T2D and obesity.


Author(s):  
A. W. Fetter ◽  
C. C. Capen

Atrophic rhinitis in swine is a disease of uncertain etiology in which infectious agents, hereditary predisposition, and metabolic disturbances have been reported to be of primary etiologic importance. It shares many similarities, both clinically and pathologically, with ozena in man. The disease is characterized by deformity and reduction in volume of the nasal turbinates. The fundamental cause for the localized lesion of bone in the nasal turbinates has not been established. Reduced osteogenesis, increased resorption related to inflammation of the nasal mucous membrane, and excessive resorption due to osteocytic osteolysis stimulated by hyperparathyroidism have been suggested as possible pathogenetic mechanisms.The objectives of this investigation were to evaluate ultrastructurally bone cells in the nasal turbinates of pigs with experimentally induced atrophic rhinitis, and to compare these findings to those in control pigs of the same age and pigs with the naturally occurring disease, in order to define the fundamental lesion responsible for the progressive reduction in volume of the osseous core.


Author(s):  
W. W. Barker ◽  
W. E. Rigsby ◽  
V. J. Hurst ◽  
W. J. Humphreys

Experimental clay mineral-organic molecule complexes long have been known and some of them have been extensively studied by X-ray diffraction methods. The organic molecules are adsorbed onto the surfaces of the clay minerals, or intercalated between the silicate layers. Natural organo-clays also are widely recognized but generally have not been well characterized. Widely used techniques for clay mineral identification involve treatment of the sample with H2 O2 or other oxidant to destroy any associated organics. This generally simplifies and intensifies the XRD pattern of the clay residue, but helps little with the characterization of the original organoclay. Adequate techniques for the direct observation of synthetic and naturally occurring organoclays are yet to be developed.


Author(s):  
G. M. Hutchins ◽  
J. S. Gardner

Cytokinins are plant hormones that play a large and incompletely understood role in the life-cycle of plants. The goal of this study was to determine what roles cytokinins play in the morphological development of wheat. To achieve any real success in altering the development and growth of wheat, the cytokinins must be applied directly to the apical meristem, or spike of the plant. It is in this region that the plant cells are actively undergoing mitosis. Kinetin and Zeatin were the two cytokinins chosen for this experiment. Kinetin is an artificial hormone that was originally extracted from old or heated DNA. Kinetin is easily made from the reaction of adenine and furfuryl alcohol. Zeatin is a naturally occurring hormone found in corn, wheat, and many other plants.Chinese Spring Wheat (Triticum aestivum L.) was used for this experiment. Prior to planting, the seeds were germinated in a moist environment for 72 hours.


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