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Interleukin-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture.

Interleukin-1 (IL-1), initially called "endogenous pyrogen," is primarily known as a mediator of inflammation. However, it also plays many other diverse physiologic roles including the stimulation and inhibition of both primary cells in culture and the interstitial and parenchymal cells of a number of organs including the heart. In the heart, IL-1 expression has traditionally been reported in situations where there is immunologic myocardial injury such as occurs during transplant rejection and congestive heart failure. For this reason, all of the effects of IL-1 have been presumed to be delete

Biochanin A Mitigates Atherosclerosis by Inhibiting Lipid Accumulation and Inflammatory Response.

Biochanin A (BCA), a dietary isoflavone extracted from red clover and cabbage, has been shown to antagonize hypertension and myocardial ischemia/reperfusion injury. However, very little is known about its role in atherogenesis. The aim of this study was to observe the effects of BCA on atherosclerosis and explore the underlying mechanisms. Our results showed that administration of BCA promoted reverse cholesterol transport (RCT), improved plasma lipid profile, and decreased serum proinflammatory cytokine levels and atherosclerotic lesion area in apoE-/- mice fed a Western diet. In THP-1 macrop

The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo- p-dioxin-mediated apoptosis in human leukemic T cell lines.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a common environmental pollutant causing public concern. Its toxic effects include disruption of the immune, endocrine, and reproductive systems, impairment of fetal development, carcinogenicity, and lethality in rodents. Here, we report that TCDD induces apoptosis in two cultured human leukemic lymphoblastic T cell lines. This cell death was found not to be dependent on an aryl hydrocarbon receptor and to be inhibited by the inhibitor of tyrosine kinases and caspases. Apoptosis-linked c-Jun N-terminal kinase is rapidly activated in these cells by

Ethanol inhibits astroglial cell proliferation by disruption of phospholipase D-mediated signaling.

The activation of phospholipase D (PLD) is a common response to mitogenic stimuli in various cell types. As PLD-mediated signaling is known to be disrupted in the presence of ethanol, we tested whether PLD is involved in the ethanol-induced inhibition of cell proliferation in rat cortical primary astrocytes. Readdition of fetal calf serum (FCS) to serum-deprived astroglial cultures caused a rapid, threefold increase of PLD activity and a strong mitogenic response; both effects were dependent on tyrosine kinases but not on protein kinase C. Ethanol (0.1-2%) suppressed the FCS-induced, PLD-media

Effects of three flavonoids from an ancient traditional Chinese medicine Radix puerariae on geriatric diseases.

As the worldwide population ages, the morbidity of neurodegenerative, cardiovascular, cerebrovascular, and endocrine diseases, such as diabetes and osteoporosis, continues to increase. The etiology of geriatric diseases is complex, involving the interaction of genes and the environment, which makes effective treatment challenging. Traditional Chinese medicine, unlike Western medicine, uses diverse bioactive ingredients to target multiple signaling pathways in geriatric diseases. Radix puerariae is one of the most widely used ancient traditional Chinese medicines and is also consumed as food. T

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… Genistein Effects on Aging-Related Disease Cardiovascular and cerebrovascular disease Genistein can attenuate neuronal degeneration caused by cerebral ischemia by reducing oxidative damage. … The anti-diabetes effects of genistein have been demonstrated in various animal models. …

Plants as a Source of Anticancer Agents: From Bench to Bedside.

Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in

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… In fact, soybean, soy-based foods, and soy-based drinks are the best sources of genistein. Lupin ( Lupinus perennis ) is also a legume that holds similar nutritional value to that of soybean in terms of genistein content. … Genistein Breast cancer incidence was found to be lower in peri-menopausal women who ate more soy food [ 395 ]. Another meta-analysis of 9000 breast cancer patients found that increasing the genistein dose reduced breast cancer risk [ 396 ]. …

Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy.

OBJECTIVE: The purpose of this study was to investigate whether prostaglandin E2 (PGE2) induces Signal transducer and activator of transcription 3 (Stat3) activation in neonatal rat ventricular cardiomyocytes and if so to determine the possible role of this activation in PGE2-induced hypertrophic responses. METHODS: Stat3 activation and its nuclear phosphorylation were determined by electrophoretic mobility shift assay (EMSA) and by Western blots, respectively. Protein synthesis was assessed by [3H]-leucine incorporation into total protein and cell surface was quantified by microscopic analys

Transduction pathways involved in rapid hormone receptor regulation in the mammary epithelium.

Previous studies have shown that the envelope protein of the mouse mammary tumor virus (MMTV) rapidly upregulates prolactin (PRL) receptors by shifting them from internal pools to the cell surface and downregulates epidermal growth factor (EGF) receptors by inducing their internalization and degradation. This study shows that the effect on PRL receptors is mediated by the nitric oxide (NO)/cGMP pathway, since it can be mimicked by an NO donor or 8-bromo-cGMP and can be blocked by an NO synthase inhibitor. In contrast, the effect on EGF receptors is mediated by tyrosine phosphorylation and phos

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

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… In fact, soybean, soy-based foods, and soy-based drinks are the best sources of genistein. Lupin ( Lupinus perennis ) is also a legume that holds similar nutritional value to that of soybean in terms of genistein content. … with high genistein content) [ 174 ]. …

Antioxidants in brain tumors: current therapeutic significance and future prospects.

Brain cancer is regarded among the deadliest forms of cancer worldwide. The distinct tumor microenvironment and inherent characteristics of brain tumor cells virtually render them resistant to the majority of conventional and advanced therapies. Oxidative stress (OS) is a key disruptor of normal brain homeostasis and is involved in carcinogenesis of different forms of brain cancers. Thus, antioxidants may inhibit tumorigenesis by preventing OS induced by various oncogenic factors. Antioxidants are hypothesized to inhibit cancer initiation by endorsing DNA repair and suppressing cancer progress

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… Genistein exhibits an anticancer effect with a mechanism comparable to that of resveratrol [ 154 ]. … Polymeric nanoformulation co-loaded with genistein and TMZ has shown promising therapeutic efficacy against GBM and exhibits synergy between genistein and TMZ [ 163 ]. …

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… The binding affinity of genistein to ERβ is about 7–48-fold higher than to ERα [ 239 , 240 , 241 ]. … There are paradoxical findings on the effect of genistein on the proliferation of ER + and ER − breast cancer cells that are associated with concentration of genistein [ 252 , 253 ]. …

Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signalin

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… Genistein may affect HCC progression as a result of its effects on cell cycle progression and apoptosis [ 172 ]. … Genistein has been reported to suppress ATK and the NF- κ B pathway through different pathways [ 98 , 99 ]. Combination of ATO with genistein presents a promising therapeutic approach for the treatment of HCC. …

Using ncRNAs as Tools in Cancer Diagnosis and Treatment-The Way towards Personalized Medicine to Improve Patients' Health.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular

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… Genistein Genistein (prunetol) is a flavonoid compound and a phytoestrogen extracted from the dyer’s broom, Genista tinctoria ; it is present in several foods of vegetable origin, including lupin, fava beans, soybeans, kudzu, psoralea, and coffee. … Also in this case, in the last years several connections have been found linking cancer, ncRNA expression, and genistein assumption. In kidney cancer cells, genistein lowers miR-21 [ 127 ], miR-23b-3p [ 128 ], and miR-1260b [ 129 ] expression. …

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with l

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… Genistein and daidzein are the most studied compounds of this subgroup in terms of medical applications. … Genistein The isoflavone most reported in medicine is genistein, which is a phytoestrogen compound produced in soybeans. Genistein was for the first time isolated in 1899. …

Predicting and Quantifying Antagonistic Effects of Natural Compounds Given with Chemotherapeutic Agents: Applications for High-Throughput Screening.

Natural products have been used for centuries to treat various human ailments. In recent decades, multi-drug combinations that utilize natural products to synergistically enhance the therapeutic effects of cancer drugs have been identified and have shown success in improving treatment outcomes. While drug synergy research is a burgeoning field, there are disagreements on the definitions and mathematical parameters that prevent the standardization and proper usage of the terms synergy, antagonism, and additivity. This contributes to the relatively small amount of data on the antagonistic effect

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… Genistein Genistein is an isoflavonoid derived from soybeans and soy-containing products, such as tofu, as well as fava beans and kudzu. Genistein supplementation (a form of CAM) is commonly used as a hormone replacement therapy alternative for postmenopausal women [ 70 ]. … Genistein has been shown to exhibit potent anticancer effects and synergize with certain cancer therapeutics [ 71 , 72 , 73 ]. …

Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.

Prostacyclin (PGI(2)), a potent smooth muscle relaxant, is a major prostaglandin secreted from human myometrium. The concentrations of PGI(2) metabolites in the maternal plasma were reported to be elevated during pregnancy, especially in labor. To clarify the mechanism in PGI(2) secretion from the myometrium, we first investigated the protein expression of cytosolic phospholipase A(2), cyclooxygenase (COX)-1, COX-2, and prostacyclin synthase (PGIS) in the human uterine myometrium at various gestational ages before labor. To elucidate the involvement of labor in the increase in PGI(2) productio

Mutations in the nucleotide binding domain 1 signature motif region rescue processing and functional defects of cystic fibrosis transmembrane conductance regulator delta f508.

The gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP binding cassette (ABC) transporter that functions as a phosphorylation- and nucleotide-regulated chloride channel, is mutated in cystic fibrosis (CF) patients. Deletion of a phenylalanine at amino acid position 508 (DeltaF508) in the first nucleotide binding domain (NBD1) is the most prevalent CF-causing mutation and results in defective protein processing and reduced CFTR function, leading to chloride impermeability in CF epithelia and heterologous systems. Using a STE6/CFTRDeltaF508 chimera system in yea

Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk-1, erk-2, and p38 in astrocytes.

Cell wall compounds of gram-positive bacteria are capable of inducing the biosynthesis of proinflammatory cytokines in CNS cells in a similar way as lipopolysaccharide (LPS) of gram-negative bacteria does. Astrocytes, which lack the CD14 LPS receptor, have also been shown to respond to LPS-stimulation by increased cytokine synthesis. However, almost nothing is known about signaling steps involved in this process. We have therefore examined signaling events in primary cultures of rat astrocytes and the human astrocytoma cell line U373MG, brought about by LPS and pneumococcal cell walls (PCW). O

Tyrosine phosphorylation controls nuclear export of Fyn, allowing Nrf2 activation of cytoprotective gene expression.

Fyn, an Src kinase family member, acts as a negative regulator of NF-E2-related factor 2 (Nrf2). Under stressful conditions, Nrf2 translocates into the nucleus and binds to the antioxidant response element (ARE), activating defensive gene expression. Once Nrf2 completes activation, Fyn phosphorylates tyrosine 568 of Nrf2, resulting in the nuclear export and degradation of Nrf2. The present studies demonstrate that within 0.5 h of antioxidant treatment in human hepatoblastoma (HepG2) cells, Fyn exports out of the nucleus, allowing Nrf2 unimpeded movement to the ARE. Mutation of tyrosine 213 of