Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 79
Filter
1.
Int J Med Sci ; 21(6): 1165-1175, 2024.
Article in English | MEDLINE | ID: mdl-38774756

ABSTRACT

Oral cancer is the most heterogeneous cancer at clinical and histological levels. PI3K/AKT/mTOR pathway was identified as one of the most commonly modulated signals in oral cancer, which regulates major cellular and metabolic activity of the cell. Thus, various proteins of PI3K/AKT/mTOR pathway were used as therapeutic targets for oral cancer, to design more specific drugs with less off-target toxicity. This review sheds light on the regulation of PI3K/AKT/mTOR, and its role in controlling autophagy and associated apoptosis during the progression and metastasis of oral squamous type of malignancy (OSCC). In addition, we reviewed in detail the upstream activators and the downstream effectors of PI3K/AKT/mTOR signaling as potential therapeutic targets for oral cancer treatment.


Subject(s)
Autophagy , Mouth Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Humans , Autophagy/physiology , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Apoptosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics
2.
Sci Rep ; 14(1): 12349, 2024 05 29.
Article in English | MEDLINE | ID: mdl-38811791

ABSTRACT

Breast cancer presents a significant challenge due to its high rates of illness and mortality, necessitating more effective treatment approaches. While traditional treatments offer some benefits, they often lack precision in targeting cancer cells and can inadvertently harm healthy tissues. This study aims to investigate the cytotoxic effects and molecular mechanism of 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone (DDR), extracted from Indigofera aspalathoides Vahl, on breast cancer cells (MDA-MB-231). Through various in vitro assays including wound healing, invasion, Western blotting, and immunofluorescence, the impact of DDR on epithelial-mesenchymal transition (EMT) and metastasis was evaluated. Treatment of MDA-MB-231 cells with different DDR concentrations (0-10 µg/mL) resulted in a significant decrease in invasion and migration, accompanied by the downregulation of metastasis-related proteins including VEGF, uPAR, uPA, and MMP-9. DDR treatment also hindered EMT by upregulating E-cadherin and downregulating N-cadherin, Slug, Twist, and Vimentin. Additionally, inhibition of the PI3K/AKT signaling pathway and downregulation of the NF-кB pathway were observed. These findings highlight the potential of DDR as a valuable source of natural compounds with promising anticancer properties, offering opportunities for the development of novel cancer therapies.


Subject(s)
Breast Neoplasms , Cell Movement , Epithelial-Mesenchymal Transition , Flavones , Indigofera , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Epithelial-Mesenchymal Transition/drug effects , Female , Cell Line, Tumor , Flavones/pharmacology , Flavones/chemistry , Flavones/isolation & purification , Indigofera/chemistry , Cell Movement/drug effects , Signal Transduction/drug effects , Neoplasm Metastasis , Proto-Oncogene Proteins c-akt/metabolism , NF-kappa B/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry
3.
Food Nutr Res ; 682024.
Article in English | MEDLINE | ID: mdl-38571915

ABSTRACT

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

5.
Noncoding RNA Res ; 9(2): 602-611, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38532798

ABSTRACT

Oral squamous cell carcinoma (OSCC) showed a seemingly increasing incidence in the last decade. In India, despite the use of tobacco decreased rapidly, in the past five years, the incidence pattern of OSCC over gender and age showed a drastic shift. About 51 % of the head and neck cancers are not associated with habits. Studies exploring various contributing factors in the incidence of this malignancy have documented. Recently, the epigenetic factors associated with the induction and progression of OSCC were explored. More than 90 % of the human genome is made up of non-coding transcriptome, which believed to be noises. However, these non-coding RNAs were identified to be the major epigenetic modulators, which raises concern over incidence of carcinoma in non-habit patients. H19 is a long non coding RNA which proved to be an effective biomarker in various carcinoma. Its role in oral squamous cell cancer was not investigated in depth. This review discusses in detail the various epigenetic role of H19 in inducing oral carcinogenesis.

6.
Aging (Albany NY) ; 16(6): 5000-5026, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38517361

ABSTRACT

D-galactose (D-gal) administration was proven to induce cognitive impairment and aging in rodents' models. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes. GNL reduces inflammation by changing important signaling pathways and cytokines, and thus it is plausible to be used as a medicine for treating disorders linked to inflammation. Herein, we examined the therapeutic effects of GNL on D-gal-induced oxidative stress and neuroinflammation-mediated memory loss in mice. The study was conducted using six groups of mice (6 mice per group). The first group received normal saline, then D-gal (150 mg/wt) dissolved in normal saline solution (0.9%, w/v) was given orally for 9 weeks to the second group. In the III group, from the second week until the 10th week, mice were treated orally (without anesthesia) with D-gal (150 mg/kg body wt) and GNL weekly twice (40 mg/kg body wt) four hours later. Mice in Group IV were treated with GNL from the second week up until the end of the experiment. For comparison of young versus elderly mice, 4 month old (Group V) and 16-month-old (Group VI) control mice were used. We evaluated the changes in antioxidant levels, PI3K/Akt levels, and Nrf2 levels. We also examined how D-gal and GNL treated pathological aging changes. Administration of GNL induced a significant increase in spatial learning and memory with spontaneously altered behavior. Enhancing anti-oxidant and anti-inflammatory effects and activating PI3K/Akt were the mechanisms that mediated this effect. Further, GNL treatment upregulated Nrf2 and HO-1 to reduce oxidative stress and apoptosis. This was confirmed using 99mTc-HMPAO brain flow gamma bioassays. Thus, our data suggested GNL as a promising agent for treating neuroinflammation-induced cognitive impairment.


Subject(s)
Acyclic Monoterpenes , Cognitive Dysfunction , Galactose , Humans , Mice , Animals , Galactose/toxicity , Proto-Oncogene Proteins c-akt/metabolism , Neuroinflammatory Diseases , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Oxidative Stress , Aging/metabolism , Cognitive Dysfunction/drug therapy , Antioxidants/pharmacology , Disease Models, Animal , Inflammation/drug therapy
7.
Saudi J Med Med Sci ; 12(1): 17-26, 2024.
Article in English | MEDLINE | ID: mdl-38362098

ABSTRACT

Background: Hepatotoxicity caused by CCL4 is well known. Geraniol (GNL) has high antioxidant effect that can induces liver regeneration. However, the protective effect of GNL effect on CCL4-induced hepatorenal toxicity in pregnant mice has not yet been studied. Objective: To investigate whether GNL could protect against oxidative stress induced by CCL4 via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which is regulated by phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and has been found to have protective effects on renal and hepatic tissues. Materials and Methods: Forty-eight female albino mice weighing 25-30 g were randomly allocated to 4 groups: Group I served as a control; Group II received a toxicity-inducing single dose of 15 µL of CCL4 on the 4th day after mating; Group III received 40 mg/kg GNL + CCL4 (with GNL from the 1st day of assimilation to delivery); and Group IV received GNL alone from the 1st day of assimilation to the end of the delivery period. GNL was evaluated for its protective effects on hepatotoxicity in CCL4-treated pregnant mice. Litter size, weight, survival rate, and resorption were recorded. In addition, H & E staining was done for liver and kidney pathology as well as biochemical markers and oxidative markers malondialdehyde, superoxide dismutase, and catalase were analyzed. Results: CCL4 significantly reduced survival rate and increased resorption after exposure. Alanine transaminase and aspartate aminotransferase concentrations in the serum, tissue MDA, blood urea nitrogen, and creatinine were increased after CCL4 exposure. GNL improved enzyme and antioxidant levels and prevented CCL4-induced hepatic injury in mice. Caspase-3 cleavage was decreased by GNL, which increased PI3K, phosphorylated AKT, Nrf2, and B-cell lymphoma 2. Conclusion: GNL demonstrates a protective effect against CCl4-induced hepatorenal toxicity, mediated through the activation of the PI3K/AKT signaling pathway and the upregulation of Nrf2. These findings highlight the potential therapeutic implications of GNL in mitigating oxidative stress and inflammation in liver and kidney tissues.

8.
Nat Prod Res ; 38(10): 1652-1661, 2024 May.
Article in English | MEDLINE | ID: mdl-37226502

ABSTRACT

An experimental study has been conducted to investigate the efficacy of geraniol (GNL) isolated from lemomgrass in protecting against cardiac toxicity induced by tilmicosin (TIL) in albino mice. Compared to TIL-treated mice, those supplemented with GNL had a thicker left ventricular wall and a smaller ventricular cavity. Studies of TIL animals treated with GNL showed that their cardiomyocytes had markedly changed in diameter and volume, along with a reduction in numerical density. After TIL induction, animals showed a significant increase in the protein expression of TGF-ß1, TNF-α, nuclear factor kappa B (NF-kB), by 81.81, 73.75 and 66.67%, respectively, and hypertrophy marker proteins ANP, BNP, and calcineurin with respective percentages of 40, 33.34 and 42.34%. Interestingly, GNL significantly decreased the TGF-ß1, TNF-α, NF-kB, ANP, BNP, and calcineurin levels by 60.94, 65.13, 52.37, 49.73, 44.18 and 36.84%, respectively. As observed from histopathology and Masson's trichrome staining, supplementation with GNL could rescue TIL-induced cardiac hypertrophy. According to these results, GNL may protect the heart by reducing hypertrophy in mice and modulating biomarkers of fibrosis and apoptosis.


Subject(s)
Acyclic Monoterpenes , Cymbopogon , Tylosin/analogs & derivatives , Mice , Animals , NF-kappa B/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Calcineurin/metabolism , Calcineurin/pharmacology , Oxidative Stress , Myocytes, Cardiac , Cardiomegaly/metabolism , Cardiomegaly/pathology
9.
Sci Rep ; 13(1): 10489, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37380735

ABSTRACT

Globally, COVID-19 affected radiopharmaceutical laboratories. This study sought to determine the economic, service, and research impacts of COVID-19 on radiopharmacy. This online survey was conducted with the participation of employees from nuclear medicine and radiopharmaceutical companies. The socioeconomic status of the individuals was collected. The study was participated by 145 medical professionals from 25 different countries. From this work, it is evident that 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG), and 99mTc-labeled macro aggregated albumin 99mTc-MAA were necessary radiopharmaceuticals used by 57% (83/145and 34% (49/145;) respondents, respectively for determining how COVID infections affect a patient's body. The normal scheduling procedure for the radiopharmacy laboratory was reduced by more than half (65%; 94/145). In COVID-19, 70% (102/145) of respondents followed the regulations established by the local departments. Throughout the pandemic, there was a 97% (141/145) decrease in all staffing recruitment efforts. The field of nuclear medicine research, as well as the radiopharmaceutical industry, were both adversely affected by COVID-19.


Subject(s)
COVID-19 , Nuclear Medicine , Humans , Radiopharmaceuticals , COVID-19/epidemiology , Radionuclide Imaging , Fluorodeoxyglucose F18
10.
Noncoding RNA Res ; 8(3): 376-384, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37250455

ABSTRACT

Oral cancer is the most debilitating disease which affects the orderly life of a human. With so much advancement in research and technology, the average life expectancy of an individual with oral cancer appears to be about 5 years. The changing trend in incidence of oral cancer among young individuals and women without tobacco habits are ascending. Non habit related oral cancer are taking centre stage and multiple factors which induce complex biology are associated in such scenarios. To decipher the aetiology and to understand the process, these cancerous conditions are to be studied at molecular level. Saliva, the most non-invasively obtained body fluid are assessed for biomarkers exclusively in liquid biopsy. This fluid gives a huge platform to study number of molecules associated with oral cancer. Non coding RNAs are transcripts with no protein coding function. They are gaining more importance in recent times. Long noncoding RNA, microRNA are major types of noncoding transcriptome that influences in progression of oral cancer. They seem to play an important role in health and disease. Apart from these, circulating tumour cells, exosomes, extracellular vesicles, antigens and other proteins can be studied from saliva. This review is aimed to update the knowledge on current biomarkers in saliva associated with oral cancer and their epigenetic role in disease progression as well recent advances in detecting these markers to identify the stage of the disease, which will help in deciding the treatment protocol.

11.
Front Pharmacol ; 14: 1103940, 2023.
Article in English | MEDLINE | ID: mdl-37180724

ABSTRACT

Background: Although aluminum (Al) is not biologically crucial to the human body, classical studies have demonstrated that excessive human exposure to Al can induce oxidative damage, neuroinflammatory conditions and neurotoxic manifestations implicated in Alzheimer's disease (AD). Exposure to Al was reported to be associated with oxidative damage, neuroinflammation, and to enhance progressive multiregional neurodegeneration in animal models. Several plant-derived natural biomolecules have been recently used to reduce the toxic effects of Al through decreasing the oxidative stress and the associated diseases. A good candidate still to be tested is an active natural furanocoumarin, the isoimperatorin (IMP) that can be extracted from Lemon and lime oils and other plants. Here, we examined the neuroprotective effects of IMP on aluminum chloride (AlCl3)-induced neurotoxicity in albino mice. Methods: Twenty-four male albino mice were used in this study. Mice were randomly devided into 5 groups. The first group was given distilled water as a control, the second group was given AlCl3 orally (10 mg/wt/day) starting from the 2nd week to the end of the 6th week, the third group received AlCl3 orally and IMP interperitoneally, i. p. (30 mg/wt/day) starting from week 2 till week 6 where IMP was supplement 1st and then 4 h later AlCl3 was given to mice. The fourth group received the control (IMP 30 mg/wt, i. p.) from the 2nd week till the end of the experiment. Rodent models of central nervous system (CNS) disorders were assessed using object location memory and Y-maze tests in 6th week began. Essential anti-inflammatory and oxidative stress indicators were evaluated, including interleukin-1 ß (IL-1ß), tumor necrosis factor α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). In addition, serum levels of brain neurotransmitters such as corticosterone, acetylcholine (ACh), dopamine and serotonin in brain homogenates were measured calorimetrically. Results: The study results revealed that the daily treatment of AlCl3 upregulated the TNF-α and IL-1ß levels, increased MDA accumulation, and decreased TAC and CAT activity. In addition, aluminum induced a reduction in concentrations of ACh, serotonin and dopamine in the brain. However, IMP significantly ameliorates the effect of AlCl3 through modulating the antioxidant and regulating the inflammatory response through targeting Nrf2 (NF-E2-related factor 2) and mitogen-activated protein kinase (MAPK). Conclusion: Thus, IMP might be a promising treatment option for neurotoxicity and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, which are associated with neuro-inflammation and oxidative stress.

12.
Nutrients ; 15(5)2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36904106

ABSTRACT

Stroke is one of the main causes of mortality and disability, and it is due to be included in monetary implications on wellbeing frameworks around the world. Ischemic stroke is caused by interference in cerebral blood flow, leading to a deficit in the supply of oxygen to the affected region. It accounts for nearly 80-85% of all cases of stroke. Oxidative stress has a significant impact on the pathophysiologic cascade in brain damage leading to stroke. In the acute phase, oxidative stress mediates severe toxicity, and it initiates and contributes to late-stage apoptosis and inflammation. Oxidative stress conditions occur when the antioxidant defense in the body is unable to counteract the production and aggregation of reactive oxygen species (ROS). The previous literature has shown that phytochemicals and other natural products not only scavenge oxygen free radicals but also improve the expressions of cellular antioxidant enzymes and molecules. Consequently, these products protect against ROS-mediated cellular injury. This review aims to give an overview of the most relevant data reported in the literature on polyphenolic compounds, namely, gallic acid, resveratrol, quercetin, kaempferol, mangiferin, epigallocatechin, and pinocembrin, in terms of their antioxidant effects and potential protective activity against ischemic stroke.


Subject(s)
Ischemic Stroke , Stroke , Humans , Antioxidants/pharmacology , Reactive Oxygen Species/metabolism , Polyphenols/pharmacology , Neuroprotection , Stroke/metabolism , Oxidative Stress , Ischemia
13.
Molecules ; 28(4)2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36838531

ABSTRACT

Trichophyton rubrum is the most common dermatophyte, and can cause cutaneous infections in humans and animals (dermatophytosis). In this study, we investigated the anti-dermatophytic potential of green synthesized silver nanoparticles using Achillea santolina extract (AS-AgNPs) in an in vitro and in vivo rat model of dermal T. rubrum dermatophytosis (TRD). The green synthesis of AS-AgNPs was performed using A. santolina extract and characterized by UV-VIS spectroscopy, zeta potential, imaging (transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Energy dispersive X-ray analysis (EDX). The antifungal activity of AS-AgNPs was determined by the broth microdilution method, conidial germination, and hyphal growth inhibition. TEM and SEM were used to study the mode of the antifungal action of AS-AgNPs. AS-AgNPs inhibited the growth of T. rubrum with an MIC of 128 µg/mL, and suppressed the conidial germination and hyphal growth by 55.3% 84.6%, respectively. AS-AgNPs caused modified mycelial structures, increased cell membrane permeability, and cell wall damage. AS-AgNPs significantly increase the permeability of the fungal membrane, as revealed by reducing ergosterol biosynthesis. An increase in the intracellular ROS and the induction of apoptosis were also observed during AS-AgNP treatment. In addition, AS-AgNPs reduced the cell wall integrity, as shown by the reduction in the ß-(1,3)-d-glucan synthase and chitin synthase activities. AS-AgNPs showed very low toxicity on primary human dermal fibroblasts (HDF) at the MIC. The topical treatment of the infected skin in the TRD rat model with AS-AgNPs showed a significant reduction in the fugal burden after 7 days and a complete clearance of fungal conidia, with a high recovery of epidermal and dermal structures after 14 days, compared to control rats. Interestingly, AS-AgNPs significantly attenuated the infiltrated inflammatory cells, in association with reducing the tissue proinflammatory cytokines including TNF-α, IL-1, IL-6, MOP and IL-17. In conclusion, our data prove AS-AgNPs to be a novel green topical therapy for dermatophytosis caused by T. rubrum.


Subject(s)
Achillea , Arthrodermataceae , Metal Nanoparticles , Tinea , Rats , Humans , Animals , Antifungal Agents/pharmacology , Metal Nanoparticles/chemistry , Silver/chemistry , Plant Extracts/chemistry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared
15.
Nutrients ; 14(22)2022 Nov 14.
Article in English | MEDLINE | ID: mdl-36432506

ABSTRACT

Among the world's leading causes of cardiovascular disease, atherosclerosis is a chronic inflammatory disorder that affects the arteries. Both vasodilation and vasoconstriction, low levels of nitric oxide and high levels of reactive oxygen species and pro-inflammatory factors characterize dysfunctional blood vessels. Hypertension, and atherosclerosis, all start with this dysfunction. Geraniol, a compound of acyclic monoterpene alcohol, found in plants such as geranium, lemongrass and rose, is a primary constituent of essential oils. It shows a variety of pharmacological properties. This study aimed to investigate the impact of geraniol on Ox-LDL-induced stress and inflammation in human umbilical vein endothelial cells. In this study, HUVECs were treated with Ox-LDL or geraniol at different dose concentrations. MTT assay, Western blot, ROS generation and DNA fragmentation were used to evaluate geraniol's effects on Ox-LDL-induced HUVECs inflammation. The results show that geraniol pre-incubation ameliorates Ox-LDL-mediated HUVECs cytotoxicity and DNA fragmentation. The geraniol inhibited the production of pro-inflammatory cytokines by Ox-LDL, including TNF-α, IL-6 and IL-1ß. In Ox-LDL-stimulated HUVECs, geraniol suppresses the nuclear translocation and activity of NF-ᴋB as well as phosphorylation of IkBα. Moreover, geraniol activated the PI3K/AKT/NRF2 pathway in HUVECs, resulting in an increase in the expression of HO-1. Taking our data together, we can conclude that, in HUVECs, geraniol inhibits Ox-LDL-induced inflammation and oxidative stress by targeting PI3/AKT/NRF2.


Subject(s)
Atherosclerosis , Cymbopogon , Humans , Heme Oxygenase-1/metabolism , Cymbopogon/metabolism , Acyclic Monoterpenes , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Up-Regulation , Signal Transduction , Anti-Inflammatory Agents/therapeutic use , Human Umbilical Vein Endothelial Cells , Atherosclerosis/metabolism , Inflammation/drug therapy , Inflammation/metabolism
16.
Int J Mol Sci ; 23(19)2022 Oct 03.
Article in English | MEDLINE | ID: mdl-36233012

ABSTRACT

Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity.


Subject(s)
Antineoplastic Agents , Curcumin , MicroRNAs , Neoplasms , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Chromatin , DNA Methylation , Epigenesis, Genetic , Gallic Acid , Histones/metabolism , Humans , Kaempferols , Mammals/metabolism , MicroRNAs/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Polyphenols/pharmacology , Polyphenols/therapeutic use , Quercetin , Resveratrol
17.
Saudi J Med Med Sci ; 10(3): 207-215, 2022.
Article in English | MEDLINE | ID: mdl-36247053

ABSTRACT

Background: Deoxynivalenol (DON) is a trichothecene mycotoxin with demonstrated cytotoxicity in several cell lines and animals, primarily owing to inflammation and reactive oxygen species accumulation. Ruscogenin (RGN), a steroidal sapogenin of Radix Ophiopogon japonicus, has significant anti-thrombotic/anti-inflammatory effects. Objective: The aim of this study was to assess the protective role of RGN against DON-induced oxidative stress, which occurs through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and is regulated by phosphoinositide 3-kinases/protein kinase B (PI3K/AKT). Methods: The effects were examined using the HepG2 cell line. RGN and DON were suspended in serum-free medium. Cells were seeded onto plates, and then RGN, DON, or both were added over 24 h in triplicates for each group. Results: RGN conferred protection against DON-exhibited cytotoxicity against HepG2 cells. RGN pretreatment downregulated the expression of DON-induced TNF-α and COX-2 and the formation of reactive oxygen species in a dose-dependent manner. RGN upregulated the expression of Nrf2 and its antioxidant proteins as well as mRNA levels of HO-1/NQO-1/HO-1/Nrf2. Similarly, treatment with DON + RGN resulted in upregulation of the pI3K/pAKT signaling pathway in a dose-dependent manner. Finally, RGN was also found to inhibit the DON-induced apoptosis by upregulating the levels of cleaved proteins and downregulating the expression of Bcl2. Conclusion: The study demonstrates that RGN suppresses hepatic cell injury induced by oxidative stress through Nrf2 via activation of the pI3K/AKT signaling pathway.

18.
Int J Mol Sci ; 23(11)2022 May 24.
Article in English | MEDLINE | ID: mdl-35682549

ABSTRACT

MicroRNA-202 (miR-202) is a member of the highly conserved let-7 family that was discovered in Caenorhabditis elegans and recently reported to be involved in cell differentiation and tumor biology. In humans, miR-202 was initially identified in the testis where it was suggested to play a role in spermatogenesis. Subsequent research showed that miR-202 is one of the micro-RNAs that are dysregulated in different types of cancer. During the last decade, a large number of investigations has fortified a role for miR-202 in cancer. However, its functions can be double-edged, depending on context they may be tumor suppressive or oncogenic. In this review, we highlight miR-202 as a potential diagnostic biomarker and as a suppressor of tumorigenesis and metastasis in several types of tumors. We link miR-202 expression levels in tumor types to its involved upstream and downstream signaling molecules and highlight its potential roles in carcinogenesis. Three well-known upstream long non-coding-RNAs (lncRNAs); MALAT1, NORAD, and NEAT1 target miR-202 and inhibit its tumor suppressive function thus fueling cancer progression. Studies on the downstream targets of miR-202 revealed PTEN, AKT, and various oncogenes such as metadherin (MTDH), MYCN, Forkhead box protein R2 (FOXR2) and Kirsten rat sarcoma virus (KRAS). Interestingly, an upregulated level of miR-202 was shown by most of the studies that estimated its expression level in blood or serum of cancer patients, especially in breast cancer. Reduced expression levels of miR-202 in tumor tissues were found to be associated with progression of different types of cancer. It seems likely that miR-202 is embedded in a complex regulatory network related to the nature and the sensitivity of the tumor type and therapeutic (pre)treatments. Its variable roles in tumorigenesis are mediated in part thought its oncogene effectors. However, the currently available data suggest that the involved signaling pathways determine the anti- or pro-tumorigenic outcomes of miR-202's dysregulation and its value as a diagnostic biomarker.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs , Biomarkers , Carcinogenesis/genetics , Cell Line, Tumor , Cell Proliferation , Forkhead Transcription Factors/metabolism , Humans , Male , Membrane Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA-Binding Proteins/metabolism
19.
Braz J Biol ; 84: e259100, 2022.
Article in English | MEDLINE | ID: mdl-35588519

ABSTRACT

The potential of Alhagi maurorum (Boiss.) aqueous extract (AME), used in traditional medicine for treatment or prevention of urolithiasis, to dissolve calcium oxalate stones in vitro was evaluated. In order to determine the litholytic potential of the extract, Calcium oxalate urinary stones were incubated during 12 weeks under continuous shaking in the presence of AME, Rowanix or NaCl 9 g/mL solution were used as controls. After the incubation period, the residual weight of the treated calculi was determined and the rate of dissolution was calculated. The medium pH variation was measured and changes in the calcium oxalate crystals at the stone surface were assessed using a scanning electron microscope (SEM). The results showed a significant dissolution effect for the extract on the kidney calculi during the experimentation period. At the end of the experiment, the percentages of calculi weight decrease were 41.23, 4.97 and 55.67% for the extract, NaCl solution and Rowanix, respectively. Gas Chromatography analysis revealed mainly the presence of the following phyto-compounds: Cyclopropenone, 2,3-diphenyl; 1-Nonadecanol; methyl-alpha-D-mannopyranoside; cis-9-Hexadecenal. These compounds unarguably play crucial roles in the health care system especially in cancer treatment and many other diseases including urolithiasis. The urinary stone dissolution, independent of medium pH, could be attributed to formation of complexes between the phytochemical compounds in the extract and the calculi.


Subject(s)
Calculi , Urolithiasis , Calcium Oxalate/chemistry , Calcium Oxalate/urine , Humans , Saudi Arabia , Sodium Chloride , Urolithiasis/urine
20.
Clin Exp Pharmacol Physiol ; 49(6): 613-623, 2022 06.
Article in English | MEDLINE | ID: mdl-35275419

ABSTRACT

In recent years, oncotherapy has received considerable attention concerning plant polyphenols. Increasing evidence suggests that because of the efficiency of polyphenols, they may have anti-tumour effects in various cancers. However, their regulatory structures remain elusive. Long non-coding RNAs (lncRNAs) have been identified in the regulation of various forms of tumorigenesis and tumour development. Long non-coding RNAs have recently emerged as regulatory eukaryotic transcripts and therapeutic targets with important and diverse functions in health and diseases. LncRNAs may be associated with the initiation, development, and progression of cancer. This review summarizes the research on the modulatory effects of IncRNAs and their roles in mediating cellular processes. The mechanisms of action of polyphenols underlying their therapeutic effects on cancers are also discussed. Based on our review, polyphenols might facilitate a significant epigenetic modification as part of their tissue- and/or cell-related biological effects. This finding may be attributed to their interaction with cellular signalling pathways involved in chronic diseases. Certain lncRNAs might be the target of specific polyphenols, and some critical signalling processes involved in the intervention of cancers might mediate the therapeutic roles of polyphenols.


Subject(s)
Neoplasms , RNA, Long Noncoding , Carcinogenesis , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Polyphenols/pharmacology , Polyphenols/therapeutic use , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Untranslated
SELECTION OF CITATIONS
SEARCH DETAIL
...