■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.

https://www.mdpi.com/2073-4409/8/10/1118/pdf

The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges.

Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

/pdf/flavonoids-as-anticancer-agents-1k0fwn93h4.pdf

Flavonoids as Anticancer Agents

A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention

Role of stereochemistry in N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) nephrotoxicity.

Enzyme induction produced by N-(3,5-dichlorophenyl)succinimide (NDPS) in rats.

Effect of calcium antagonism by nifedipine and chlorpromazine on acute n-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in fischer 344 rats

The kidney has been identified as the specific target organ for in vivo exposure to an agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS). The goal of this study was to determine if urinary protein and enzyme excretion were sensitive, non-invasive markers for NDPS-induced renal damage. The proximal tubular enzymes that were monitored were the brush-border enzyme alkaline phosphatase (ALP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG). Male Fischer 344 (F344) rats were injected intraperitoneally (i.p.) with 0.2 or 1.0 mmol kg-1 NDPS. Control animals were injected i.p. with sesame oil (2.5 ml kg-1). Urine was collected on ice 0-3, 3-6 and 6-24 h after NDPS or vehicle injection. Urinary protein and urinary NAG excretion levels were elevated (P < 0.05) above the control levels 0-3 h after treatment with 0.2 mmol kg-1 NDPS. Urinary protein and enzyme excretion was comparable between 0.2 mmol kg-1 NDPS-treated and control groups for all other time periods. Administration of a marked nephrotoxicant dose (1.0 mmol kg-1) was associated with elevated levels of urinary protein, NAG and ALP beginning 0-3 h after treatment when compared to the control group or to respective baseline values. It was concluded from these studies that measurement of urinary protein as well as the release of ALP and NAG were sensitive markers of renal damage produced by NDPS.

Urinary enzyme excretion as a parameter for detection of acute renal damage mediated by N-(3,5-dichlorophenyl)succinimide (NDPS) in Fischer 344 rats.

Enantiomerically pure N-(3,5-dichlorophenyl)-2-hydroxysuccinimides (NDHS) and N-(3,5-dichlorophenyl)-2-hydroxysuccinimide-O-sulfates (NSC) have been synthesized in our laboratory in order to address their selectively related nephrotoxic mechanism. The key step for NDHS synthesis is the intramolecular nucleophilic cyclization via the amide N-atom with retention of configuration of the original stereogenic center. The corresponding sulfate conjugates (R)-NSC and (S)-NSC were prepared by reaction of enantiomeric NDHS with chlorosulfonic acid at -78 °C.

Synthesis of Enantiopure N-(3,5-Dichlorophenyl)-2-hydroxysuccinimides (NDHS) and N-(3,5-Dichlorophenyl)-2-hydroxysuccinimide-O-sulfates (NSC)

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Gary O. Rankin

Author Tools

Chat about Author