The present state and future outlook of pectin-based nanoparticles in the stabilization of Pickering emulsions.

The stabilization of Pickering emulsions using micro/nanoparticles has gained significant attention due to their wide range of potential applications in industries such as cosmetics, food, catalysis, tissue engineering, and drug delivery. There is a growing demand for the development of environmentally friendly micro/nanoparticles to create stable Pickering emulsions. Naturally occurring polysaccharides like pectin offer promising options as they can assemble at oil/water interfaces. This polysaccharide is considered a green candidate because of its biodegradability and renewable nature. The physicochemical properties of micro/nanoparticles, influenced by fabrication methods and post-modification techniques, greatly impact the characteristics and applications of the resulting Pickering emulsions. This review focuses on recent advancements in Pickering emulsions stabilized by pectin-based micro/nanoparticles, as well as the application of functional materials in delivery systems, bio-based films and 3D printing using these emulsions as templates. The effects of micro/nanoparticle properties on the characteristics of Pickering emulsions and their applications are discussed. Additionally, the obstacles that currently hinder the practical implementation of pectin-based micro/nanoparticles and Pickering emulsions, along with future prospects for their development, are addressed.

Epigallocatechin-3-gallate and cancer: focus on the role of microRNAs.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that affect gene expression. The role of miRNAs in different types of cancers has been published and it was shown that several miRNAs are inappropriately expressed in different cancers. Among the mechanisms that can cause this lack of proper expression are epigenetics, chromosomal changes, polymorphisms or defects in processing proteins. Recent research shows that phytochemicals, including epigallocatechin-3-gallate (EGCG), exert important epigenetic-based anticancer effects such as pro-apoptotic or anti proliferative through miRNA gene silencing. Given that EGCG is able to modulate a variety of cancer-related process i.e., angiogenesis, proliferation, metastasis and apoptosis via targeting various miRNAs such as let-7, miR-16, and miR-210. The discovery of new miRNAs and the differences observed in their expression when exposed to EGCG provides evidence that targeting these miRNAs may be beneficial as a form of treatment. In this review, we aim to provide an overview, based on current knowledge, on how phytochemicals, including epigallocatechin-3-gallate, can be considered as potential miRNAs modulator to improve efficacy of current cancer treatments.

Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Video abstract.

Targeting long non coding RNA by natural products: Implications for cancer therapy.

In spite of achieving substantial progress in its therapeutic strategies, cancer-associated prevalence and mortality are persistently rising globally. However, most malignant cancers either cannot be adequately diagnosed at the primary phase or resist against multiple treatments such as chemotherapy, surgery, radiotherapy as well as targeting therapy. In recent decades, overwhelming evidences have provided more convincing words on the undeniable roles of long non-coding RNAs (lncRNAs) in incidence and development of various cancer types. Recently, phytochemical and nutraceutical compounds have received a great deal of attention due to their inhibitory and stimulatory effects on oncogenic and tumor suppressor lncRNAs respectively that finally may lead to attenuate various processes of cancer cells such as growth, proliferation, metastasis and invasion. Therefore, application of phytochemicals with anticancer characteristics can be considered as an innovative approach for treating cancer and increasing the sensitivity of cancer cells to standard prevailing therapies. The purpose of this review was to investigate the effect of various phytochemicals on regulation of lncRNAs in different human cancer and evaluate their capabilities for cancer treatment and prevention.

Quercetin: an effective polyphenol in alleviating diabetes and diabetic complications.

Various studies, especially in recent years, have shown that quercetin has beneficial therapeutic effects in various human diseases, including diabetes. Quercetin has significant anti-diabetic effects and may be helpful in lowering blood sugar and increasing insulin sensitivity. Quercetin appears to affect many factors and signaling pathways involved in insulin resistance and the pathogenesis of type 2 of diabetes. TNFα, NFKB, AMPK, AKT, and NRF2 are among the factors that are affected by quercetin. In addition, quercetin can be effective in preventing and ameliorating the diabetic complications, including diabetic nephropathy, cardiovascular complications, neuropathy, delayed wound healing, and retinopathy, and affects the key mechanisms involved in the pathogenesis of these complications. These positive effects of quercetin may be related to its anti-inflammatory and anti-oxidant properties. In this article, after a brief review of the pathogenesis of insulin resistance and type 2 diabetes, we will review the latest findings on the anti-diabetic effects of quercetin with a molecular perspective. Then we will review the effects of quercetin on the key mechanisms of pathogenesis of diabetes complications including nephropathy, cardiovascular complications, neuropathy, delayed wound healing, and retinopathy. Finally, clinical trials investigating the effect of quercetin on diabetes and diabetes complications will be reviewed.

Vitamin D in respiratory viral infections: a key immune modulator?

Respiratory viral infections are common respiratory diseases. Influenza viruses, RSV and SARS-COV2 have the potential to cause severe respiratory infections. Numerous studies have shown that unregulated immune response to these viruses can cause excessive inflammation and tissue damage. Therefore, regulating the antiviral immune response in the respiratory tract is of importance. In this regard, recent years studies have emphasized the importance of vitamin D in respiratory viral infections. Although, the most well-known role of vitamin D is to regulate the metabolism of phosphorus and calcium, it has been shown that this vitamin has other important functions. One of these functions is immune regulation. Vitamin D can regulate the antiviral immune response in the respiratory tract in order to provide an effective defense against respiratory viral infections and prevention from excessive inflammatory response and tissue damage. In addition, this vitamin has preventive effects against respiratory viral infections. Some studies during the COVID-19 pandemic have shown that vitamin D deficiency may be associated with a higher risk of mortality and sever disease in patients with COVID-19. Since, more attention has recently been focused on vitamin D. In this article, after a brief overview of the antiviral immune response in the respiratory system, we will review the role of vitamin D in regulating the antiviral immune response comprehensively. Then we will discuss the importance of this vitamin in influenza, RSV, and COVID-19.

The effects of spirulina intake on clinical and metabolic parameters in Alzheimer's disease: A randomized, double-blind, controlled trial.

The current study aimed to determine the effects of spirulina intake on cognitive function and metabolic status among patients with Alzheimer's disease (AD). This randomized, double-blind, controlled clinical trial was done among 60 subjects with AD. Patients were randomly assigned to receive either 500 mg/day spirulina or a placebo (each n = 30) twice a day for 12 weeks. Mini-mental state examination score (MMSE) was recorded in all patients before and after intervention. Blood samples were obtained at baseline and after 12 weeks' intervention to determine metabolic markers. Compared with placebo, spirulina intake resulted in a significant improvement in MMSE score (spirulina group: +0.30 ± 0.99 vs. Placebo group: -0.38 ± 1.06, respectively, p = 0.01). In addition, spirulina intake decreased high-sensitivity C-reactive protein (hs-CRP) (spirulina group: -0.17 ± 0.29 vs. Placebo group: +0.05 ± 0.27 mg/L, p = 0.006), fasting glucose (spirulina group: -4.56 ± 7.93 vs. Placebo group: +0.80 ± 2.95 mg/dL, p = 0.002), insulin (spirulina group: -0.37 ± 0.62 vs. Placebo group: +0.12 ± 0.40 µIU/mL, p = 0.001) and insulin resistance (spirulina group: -0.08 ± 0.13 vs. Placebo group: 0.03 ± 0.08, p = 0.001), and increased insulin sensitivity (spirulina group: +0.003 ± 0.005 vs. Placebo group: -0.001 ± 0.003, p = 0.003) compared with the placebo. Overall, our study showed that spirulina intake for 12 weeks in patients with AD improved cognitive function, glucose homeostasis parameters, and hs-CRP levels.

Therapeutic effect of probiotics on metabolic indices and clinical signs in age-related macular degeneration.

Probiotics positively influence age-related macular degeneration (ARMD) given their propensity to attenuate oxidative and inflammatory stress. We addressed the impact of probiotics on metabolic profiles, clinical indices, inflammatory and oxidative stress parameters in ARMD patients. We performed a randomized, double-blind, placebo-controlled trial analyzing 57 subjects with ARMD aged between 50 and 85 years. Subjects were randomized into two groups, and received daily for 8 weeks either probiotic capsule or placebo. Fasting blood samples were obtained at baseline and after the 8-week intervention for the determination of metabolic profiles and oxidative stress biomarkers. After the 8-week intervention, compared with the placebo, probiotic supplementation significantly increased means HDL-cholesterol (Probiotic group: +3.86±4.42 vs. Placebo group: -0.55±4.93 mg/dL, P = .001), plasma total antioxidant capacity (TAC) (Probiotic group: +77.43±168.30 vs. Placebo group: -23.12±169.22 mmol/L, P = .02) and significantly decreased malondialdehyde (MDA) levels (Probiotic group: -0.18±0.46 vs. Placebo group: +0.18±0.25 µmol/L, P = .001). There was no significant effect of probiotic administration on other metabolic profiles and clinical symptoms. Overall, an eight-week probiotic administration among ARMD patients had beneficial effects on TAC, MDA and HDL-cholesterol levels; however, it did not affect clinical signs and other metabolic profiles.

DNA damage response signaling pathways as important targets for combination therapy and chemotherapy sensitization in osteosarcoma.

Osteosarcoma (OS) is the most common bone malignancy that occurs most often in young adults, and adolescents with a survival rate of 20% in its advanced stages. Nowadays, increasing the effectiveness of common treatments used in OS has become one of the main problems for clinicians due to cancer cells becoming resistant to chemotherapy. One of the most important mechanisms of resistance to chemotherapy is through increasing the ability of DNA repair because most chemotherapy drugs damage the DNA of cancer cells. DNA damage response (DDR) is a signal transduction pathway involved in preserving the genome stability upon exposure to endogenous and exogenous DNA-damaging factors such as chemotherapy agents. There is evidence that the suppression of DDR may reduce chemoresistance and increase the effectiveness of chemotherapy in OS. In this review, we aim to summarize these studies to better understand the role of DDR in OS chemoresistance in pursuit of overcoming the obstacles to the success of chemotherapy.

Molecular mechanisms involved in DNA repair in human cancers: An overview of PI3k/Akt signaling and PIKKs crosstalk.

The cellular genome is frequently subjected to abundant endogenous and exogenous factors that induce DNA damage. Most of the Phosphatidylinositol 3-kinase-related kinases (PIKKs) family members are activated in response to DNA damage and are the most important DNA damage response (DDR) proteins. The DDR system protects the cells against the wrecking effects of these genotoxicants and repairs the DNA damage caused by them. If the DNA damage is severe, such as when DNA is the goal of chemo-radiotherapy, the DDR drives cells toward cell cycle arrest and apoptosis. Some intracellular pathways, such as PI3K/Akt, which is overactivated in most cancers, could stimulate the DDR process and failure of chemo-radiotherapy with the increasing repair of damaged DNA. This signaling pathway induces DNA repair through the regulation of proteins that are involved in DDR like BRCA1, HMGB1, and P53. In this review, we will focus on the crosstalk of the PI3K/Akt and PIKKs involved in DDR and then discuss current achievements in the sensitization of cancer cells to chemo-radiotherapy by PI3K/Akt inhibitors.

The effect of nutraceuticals on multiple signaling pathways in cardiac fibrosis injury and repair.

Cardiac fibrosis is one of the most common pathological conditions caused by different heart diseases, including myocardial infarction and diabetic cardiomyopathy. Cardiovascular disease is one of the major causes of mortality worldwide. Cardiac fibrosis is caused by different processes, including inflammatory reactions and oxidative stress. The process of fibrosis begins by changing the balance between production and destruction of extracellular matrix components and stimulating the proliferation and differentiation of cardiac fibroblasts. Many studies have focused on finding drugs with less adverse effects for the treatment of cardiovascular disease. Some studies show that nutraceuticals are effective in preventing and treating diseases, including cardiovascular disease, and that they can reduce the risk. However, big clinical studies to prove the therapeutic properties of all these substances and their adverse effects are lacking so far. Therefore, in this review, we tried to summarize the knowledge on pathways and mechanisms of several nutraceuticals which have shown their usefulness in the prevention of cardiac fibrosis.

From inflammatory bowel disease to colorectal cancer: what's the role of miRNAs?

Inflammatory Bowel Disease (IBD) is a chronic inflammatory disease with relapse and remission periods. Ulcerative colitis and Crohn's disease are two major forms of the disease. IBD imposes a lot of sufferings on the patient and has many consequences; however, the most important is the increased risk of colorectal cancer, especially in patients with Ulcerative colitis. This risk is increased with increasing the duration of disease, thus preventing the progression of IBD to cancer is very important. Therefore, it is necessary to know the details of events contributed to the progression of IBD to cancer. In recent years, the importance of miRNAs as small molecules with 20-22 nucleotides has been recognized in pathophysiology of many diseases, in which IBD and colorectal cancer have not been excluded. As a result, the effectiveness of these small molecules as therapeutic target is hopefully confirmed. This paper has reviewed the related studies and findings about the role of miRNAs in the course of events that promote the progression of IBD to colorectal carcinoma, as well as a review about the effectiveness of some of these miRNAs as therapeutic targets.

DNA repair and damage pathways in mesothelioma development and therapy.

Malignant mesothelioma (MMe) is an aggressive neoplasm that occurs through the transformation of mesothelial cells. Asbestos exposure is the main risk factor for MMe carcinogenesis. Other important etiologies for MMe development include DNA damage, over-activation of survival signaling pathways, and failure of DNA damage response (DDR). In this review article, first, we will describe the most important signaling pathways that contribute to MMe development and their interaction with DDR. Then, the contribution of DDR failure in MMe progression will be discussed. Finally, we will review the latest MMe therapeutic strategies that target the DDR pathway.

Circular RNAs and glioblastoma multiforme: focus on molecular mechanisms.

Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/ß-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM. Video Abstract.

The Effects of Sterol-Related Signaling Pathways on Glioma.

Gliomas are considered as one of the important brain tumors in adults due to their impact on life quality and cognitive functions. Current methods that are used for treating glioma are not satisfying enough. Understanding cellular and molecular events underlying its pathogenesis and progression may lead to the discovery of novel therapeutic approaches. Sterols are a subtype of steroids and are essential for the physiologic functions of eukaryotic cells. Sterols can be produced by protozoans and microheterotrophs. Moreover, they are found in some natural sources, such as plants, animals, fungi, microalgae, and yeasts. Besides the roles of sterols in physiologic processes, studies have shown that they are involved in pathologic processes, including tumorigenesis and tumor progression. As investigations have revealed, sterol-related signaling pathways are involved in glioma and targeting them may result in new therapeutic options for patients. Thus, we summarized some of the sterol-related signaling pathways in glioma and how they can be associated with other signaling pathways, including EGFR/PI3K/Akt/mTOR, P53, and retinoblastoma protein.

Targeting microRNAs by curcumin: implication for cancer therapy.

In spite of all the investigations in the past 20 years that established a great body of knowledge in cancer therapy, utilizing some elderly methods such as plant compound administration might still be useful. Curcumin is a bioactive polyphenol, which has many anticancer properties but its capability in modulating miRNA expression has opened new doors in the field of cancer-targeted therapy. MiRNAs are a class of small noncoding RNAs that are able to regulate gene expression and signaling. In addition, some other effects of these RNAs such as modulating cell differentiation and regulation of cell cycle have made miRNAs great candidates for personalized cancer treatment. In this review, we try to find some answers to the questions on how curcumin exerts its impacts on cancer hallmarks through miRNAs and whether chemotherapy can be replaced by this beneficial plant compound.

The role of dietary polyphenols in alternating DNA methylation in cancer.

Natural products such as curcumin, quercetin, and resveratrol have been shown to have antitumor effectsand several studies have examined their role in treating cancer, either alone or in combination with other chemotherapeutic drugs. These compounds are capable of affecting different cancer-related mechanisms, such as proliferation, inflammation, invasion, and metastasis. Along with all of the benefits of these agents, affecting epigenetic processes is one of the most important aspects of their impact. Epigenetic modifications can be categorized into three main processes that include DNA methylation, histone modification, and regulation of small non-coding RNAs. Therefore, targeting DNA methylation can be used as a cancer treatment strategy by identifying or developing methylation modulators. Herein, we take a look into the studies investigating the role of natural products (e.g. curcumin, resveratrol, epigallocatechin gallate (EGCG), and quercetin) in alternating the DNA methylation status of various cancer cells. We discuss how these compounds reduce the expression of enzymes mediating the methylation of tumor suppressor genes and thereby, increasing the expression of tumor suppressors while reactivating antitumor signaling pathways.

Polyphenols target miRNAs as a therapeutic strategy for diabetic complications.

MiRNAs are a large group of non-coding RNAs which participate in different cellular pathways like inflammation and oxidation through transcriptional, post-transcriptional, and epigenetic regulation. In the post-transcriptional regulation, miRNA interacts with the 3'-UTR of mRNAs and prevents their translation. This prevention or dysregulation can be a cause of pathological conditions like diabetic complications. A huge number of studies have revealed the association between miRNAs and diabetic complications, including diabetic nephropathy, cardiomyopathy, neuropathy, retinopathy, and delayed wound healing. To address this issue, recent studies have focused on the use of polyphenols as selective and safe drugs in the treatment of diabetes complications. In this article, we will review the involvement of miRNAs in diabetic complications' occurrence or development. Finally, we will review the latest findings on targeting miRNAs by polyphenols like curcumin, resveratrol, and quercetin for diabetic complications therapy.

Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.

Despite great advances, therapeutic approaches of osteosarcoma, the most prevalent class of preliminary pediatric bone tumors, as well as bone-related malignancies, continue to demonstrate insufficient adequacy. In recent years, a growing trend toward applying natural bioactive compounds, particularly phytochemicals, as novel agents for cancer treatment has been observed. Bioactive phytochemicals exert their anticancer features through two main ways: they induce cytotoxic effects against cancerous cells without having any detrimental impact on normal cell macromolecules such as DNA and enzymes, while at the same time combating the oncogenic signaling axis activated in tumor cells. Thymoquinone (TQ), the most abundant bioactive compound of Nigella sativa, has received considerable attention in cancer treatment owing to its distinctive properties, including apoptosis induction, cell cycle arrest, angiogenesis and metastasis inhibition, and reactive oxygen species (ROS) generation, along with inducing immune system responses and reducing side effects of traditional chemotherapeutic drugs. The present review is focused on the characteristics and mechanisms by which TQ exerts its cytotoxic effects on bone malignancies.

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review.

Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).