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.

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.

Chitosan as possible inhibitory agents and delivery systems in leukemia.

Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.

Are anti-inflammatory agents and nutraceuticals - novel inhibitors of PCSK9?

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease which increases the lysosomal degradation of low density lipoprotein receptor (LDLR) resulting in elevated serum LDL-cholesterol levels. Elevated LDL-cholesterol is the main risk factor for cardiovascular disease (CVD). Antibodies to PCSK9 decrease LDL-cholesterol. Recent studies have suggested a direct relationship between PCSK9 and inflammation and the potential inhibitory effects of anti-inflammatory agents against this enzyme. Nutraceuticals are natural compounds, which have numerous anti-inflammatory and lipid-lowering effects. In this review we focus on anti-inflammatory substances and nutraceuticals, which are beneficial in treatment of dyslipidemia. We also reviewed the recent findings concerning the role of PCSK9 as the main target for molecular mechanisms of these substances.

Cardiac fibrosis and curcumin: a novel perspective on this natural medicine.

BACKGROUND: According to WHO statistics, cardiovascular disease are the leading causes of death in the world. One of the main factors which is causing heart failure, systolic and diastolic dysfunction, and arrythmias is a condition named cardiac fibrosis. This condition is defined by the accumulation of fibroblast-produced ECM in myocardium layer of the heart. OBJECTIVE: Accordingly, the current review aims to depict the role of curcumin in the regulation of different signaling pathways that are involved in cardiac fibrosis. RESULTS: A great number of cellular and molecular mechanisms such as oxidative stress, inflammation, and mechanical stress are acknowledged to be involved in cardiac fibrosis. Despite the available therapeutic procedures which are designed to target these mechanisms in order to prevent cardiac fibrosis, still, effective therapeutic methods are needed. Curcumin is a natural Chinese medicine which currently has been declared to have therapeutic properties such as anti-oxidant and immunomodulatory activities. In this review, we have gathered several experimental studies in order to represent diverse impacts of this turmeric derivative on pathogenic factors of cardiac fibrosis. CONCLUSION: Curcumin might open new avenues in the field of cardiovascular treatment.

Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes.

Studies have shown that despite the decreasing mortality rates of kidney cancer patients, its incidence is increasing. Therefore, a comprehensive re-evaluation of treatment options is necessary to provide appropriate treatments for the increasing number of patients. Moreover, the side effects caused by surgery, which is the main treatment of this disease, may lead to higher morbidity rates. Consequently, new safer approaches must be examined and considered. Major advancements have been made in the field of targeted agents as well as treatments based on immunotherapy since renal cell carcinoma (RCC) does not respond well to chemotherapy. While the therapeutic options for this cancer are increasing, the resulting complexity of selecting the best strategy for treating the patients is daunting. Moreover, each therapeutic option must be evaluated concerning toxicity, cost, and clinical advantages. Several characteristics, which are beneficial for cancer therapies have been attributed to melatonin. For decades, investigations have explored the application of melatonin in the treatment of cancer; insufficient attention has been paid to this molecule at the clinical level. Melatonin plays a role in cancer therapy due to its anti-tumor effects as well as by enhancing the efficacy of other drugs as an adjuvant. In this review, we discuss different roles of melatonin in the treatment of kidney cancer. The studies concerned with the applications of melatonin as an adjuvant in the immunotherapy of patients with kidney cancer are summarized. Also, we highlight the apoptotic and anti-angiogenic effects of melatonin on renal cancer cells which are mediated by different molecules (e.g., HIF-1 and VEGF, ADAMTS1, and MMP-9) and signaling pathways (e.g., P56, P52, and JNK). Furthermore, we take a look into available data on melatonin's ability to reduce the toxicities caused by kidney carcinogens, including ochratoxin A, potassium bromate, and Fe-NTA.

Effects of Nigella sativa on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials.

The aim of this systematic review and meta-analysis was to evaluate the effects of Nigella sativa (N. sativa) on glycemic control, lipid profiles, and biomarkers of inflammatory and oxidative stress. Two independent authors systematically examined online databases consisting of, EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until October 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of the studied trials. The heterogeneity among the included studies were assessed using the Cochrane's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. A total of 50 trials were included in this meta-analysis. We found a significant reduction in total cholesterol (WMD: -16.80; 95% CI: -21.04, -12.55), triglycerides (WMD: -15.73; 95% CI: -20.77, -10.69), LDL-cholesterol (WMD: -18.45; 95% CI: -22.44, -14.94) and VLDL-cholesterol (WMD: -3.72; 95% CI: -7.27, -0.18) following supplementation with N. sativa. In addition, there was significant reductive effect observed with N. sativa on fasting glucose (WMD: -15.18; 95% CI: -19.82, -10.55) and HbA1C levels (WMD: -0.45; 95% CI: -0.66, -0.23). Effects of N. sativa on CRP (WMD: -3.61; 95% CI: -9.23, 2.01), TNF-α (WMD: -1.18; 95% CI: -3.23, 0.86), TAC (WMD: 0.31; 95% CI: 0.00, 0.63), and MDA levels (WMD: -0.95; 95% CI: -2.18, 0.27) were insignificant. This meta-analysis demonstrated the beneficial effects of N. sativa on fasting glucose, HbA1c, triglycerides, total-, VLDL-, LDL-cholesterol levels.

The effects of curcumin supplementation on endothelial function: A systematic review and meta-analysis of randomized controlled trials.

Impaired endothelial function is an important risk factor for cardiovascular disease (CVD). Curcumin supplementation might be an appropriate approach to decrease the complications of CVD. Randomized controlled trials assessing the effects of curcumin supplementation on endothelial function were included. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneities were estimated using the Cochran's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model, and weighted mean differences (WMDs) were considered as the overall effect sizes. Ten studies with 11 effect sizes were included. We found a significant increase in flow-mediated dilation (FMD) following curcumin supplementation (WMD: 1.49; 95% CI [0.16, 2.82]). There was no effect of curcumin supplement on pulse wave velocity (PWV; WMD: -41.59; 95% CI [-86.59, 3.42]), augmentation index (Aix; WMD: 0.71; 95% CI [-1.37, 2.79]), endothelin-1 (ET-1; WMD: -0.30; 95% CI [-0.96, 0.37]), and soluble intercellular adhesion molecule-1 (sICAM-1; WMD: -10.11; 95% CI [-33.67, 13.46]). This meta-analysis demonstrated the beneficial effects of curcumin supplementation on improving FMD, though it did not influence PWV, Aix, Et-1, and sICAM-1.

Understanding the Roles of Non-coding RNAs and Exosomal Non-Coding RNAs in Diabetic Nephropathy.

One of the greatest serious side effects of diabetes is diabetic nephropathy (DN), which is also the key factor in the sometimes-deadly diabetic end-stage renal disease. Progressive renal interstitial fibrosis is closely associated with oxidative stress, and the extracellular matrix is typically a feature of DN. Some RNAs formed by genome transcription that are not translated into proteins are recognized as noncoding RNAs. It has been shown that ncRNAs control apoptosis, inflammatory response, cell proliferation, autophagy, and other pathogenic processes, contributing to the pathogenesis of DN. Exosomes are nano-carriers vesicles that variety in size from 40 to 160 nm. Exosomes are widely present and dispersed in different bodily fluids, plentiful in nucleic acids, lipids, and proteins (microRNA, mRNA, tRNA, lncRNA, circRNA, etc.). Exosomes play a crucial role as messengers for cellular communication. They transport and transmit key signaling molecules, participate in the transfer of information and materials between cells, control cellular physiological processes, and are carefully linked to the beginning and development of many diseases. Herein, we summarized the role of different ncRNAs in DN. Moreover, we highlighted the role of the exosomal form of ncRNAs in the DN pathogenesis.

CircRNAs: A Novel Strategy in Diagnosis and Treatment of Thyroid Cancer.

Thyroid cancer is one of the most frequent cancers globally, and its incidence has risen recently. The clinical behavior of thyroid cancer includes a wide range, from benign to invasive malignant tumors. Thus, precious diagnostic activities before therapeutic work are required. Circular RNAs (circRNAs) along with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are known as non-coding RNAs (ncRNAs). Large amounts of investigations have indicated that circRNAs can participate in multiple cellular processes, especially in tumorigenesis. Furthermore, circRNAs are stable in blood or plasma, as well as they are specific in different tissues. Therefore, they could serve as a potential diagnostic biomarker for cancer cells. Limited studies investigated the role of circRNAs in some processes involved in thyroid cancer. In this review, we summarized the current evidence on the potential clinical involvement of circRNAs in thyroid cancer.

Advances in chitosan-based drug delivery systems in melanoma: A narrative review.

Melanoma accounts for the minority of skin cancer cases. However, it has the highest mortality rate among the subtypes of skin cancer. At the early stages of the disease, patients show a good prognosis after the surgery, but developing metastases leads to a remarkable drop in patients' 5-year survival rate. Despite the advances made in the therapeutic approaches to this disease, melanoma treatment is still facing several obstacles. Systemic toxicity, water insolubility, instability, lack of proper biodistribution, inadequate cellular penetration, and rapid clearance are some of the challenges that should be addressed in the field of melanoma treatment. While various delivery systems have been developed to circumvent these challenges, chitosan-based delivery platforms have indicated significant success. Chitosan that is produced by the deacetylation of chitin can be formulated into different materials (e.g., nanoparticle, film, and hydrogel) due to its characteristics. Both in vitro and in vivo studies have reported that chitosan-based materials can be used in drug delivery systems while offering a solution for the common problems in this area, such as enhancing biodistribution and skin penetration as well as the sustained release of the drugs. Herein, we reviewed the studies concerning the role of chitosan as a drug delivery system in melanoma and discussed how these drug systems are used for delivering chemotherapeutic drugs (e.g., doxorubicin and paclitaxel), genes (e.g., TRAIL), and RNAs (e.g., miRNA199a and STAT3 siRNA) successfully. Furthermore, we take a look into the role of chitosan-based nanoparticles in neutron capture therapy.

Resveratrol and Cardiac Fibrosis Prevention and Treatment.

Cardiovascular diseases are some of the major causes of morbidity and mortality in developed and developing countries. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models show that resveratrol has beneficial effects on cardiovascular diseases, including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.

Cervical Cancer and Novel Therapeutic and Diagnostic Approaches using Chitosan as a Carrier: A Review.

In our knowledge, using appropriate carriers in the delivery of chemotherapeutic drugs, would result in better targeting and therefore it would increase the effectiveness and decrease the side effects of drugs. Chitosan, a natural polymer derived from chitin, has attracted the attention of pharmaceutical industries recently. New research works show that chitosan can not only be used in drug delivery but it can also have some usages in the prevention and diagnosis of cancer. This means that using chitosan Nanoformulations can be a promising approach for prevention, diagnosis, and specially treatment of cervical cancer, the fourth common cancer among the women of the world. We aim to investigate the related papers to find a novel method and preventing more women from suffering.

Beta-glucans is a Potential Inhibitor of Ovarian Cancer: Based on Molecular and Biological Aspects.

Ovarian cancer is a lethal type of cancer which is initiated to the ovaries and affects 1 out of every 75 women. Due to the high number of deaths (almost 152,000) related to this cancer, it seems that novel efficient therapeutic methods are required in this field. Beta-glucans are a type of glucose linear polymers which have been proven to have a lot of advantageous activities. Recently, investigations have declared that these polysaccharides have the potential to be used as anti-cancer drugs. These agents are able to affect several mechanisms such as inflammation and apoptosis, and that is how cancers are prone to be affected by them. In this review, we attempt to investigate the role of beta-glucans on ovarian cancer. We hope that this paper would give some novel insights into the field of ovarian cancer treatment.

Effects of Berberine on Leukemia with a Focus on Its Molecular Targets.

Leukemia is common among both women and men worldwide. Besides the fact that finding new treatment methods may enhance the life quality of patients, there are several problems that we face today in treating leukemia patients, such as drugs' side effects and acquired resistance to chemotherapeutic drugs. Berberine is a bioactive alkaloid found in herbal plants (e.g., Rhizoma coptidis and Cortex phellodendri) and exerts several beneficial functions, including anti-tumor activities. Furthermore, berberine exerts antiproliferative and anti-inflammatory effects. Up to now, some studies have investigated the roles of berberine in different types of leukemia, including acute myeloid leukemia and chronic lymphocytic leukemia. In this review, a detailed description of the roles of berberine in leukemia is provided. We discuss how berberine involves different molecular targets (e.g., interleukins and cyclins) and signaling pathways (e.g., mTOR and PI3K) to exert its anti-tumor functions and how berberine is effective in leukemia treatment when combined with other therapeutic drugs.

Severe acute respiratory syndrome and thyroid: A molecular point of view.

SARS-CoV-2 and some other members of Coronaviridae family have recently forced a great deal of health, social, and economic issues globally. To that end, investigations have been oriented towards finding ways for reducing the burden of COVID-19. One of the occurrences which stands in the way of making the treatment of this disease less complicated is the way coronaviruses involve a variety of cells, tissues, organs, and even systems. This action is possible as a result of viral attachment to the angiotensin-converting enzyme 2 or ACE2. Thus, any kind of cell expressing ACE2 is prone to be affected by both SARS-COV and SARS-COV-2. Endocrine system is one of these at-risk systems. In this review, we have considered the relation between coronaviruses and one of the most essential organs of endocrine system: thyroid gland. This relation can be probed from two aspects: how underlying thyroid dysfunction can increase the risk of being infected by these viruses and how these viruses can alter the function of thyroid gland.

Effect of Lactobacillus delbrueckii Subsp. lactis PTCC1057 on Serum Glucose, Fetuin-A ,and Sestrin 3 Levels in Streptozotocin-Induced Diabetic Mice.

Intake of probiotic bacteria may improve or preserve insulin sensitivity. Fetuin-A and sestrin 3 have emerged as promising candidate biomarkers for crucial roles in insulin signaling pathway. Therefore, the effect of oral supplementation with the probiotic bacterium Lactobacillus delbrueckii subsp. lactis PTCC1057 on proteins involved in insulin signaling pathway was investigated in normal and streptozotocin (STZ)-induced diabetic mice. The 6-8-week-old female mice were divided into a non-diabetic control, diabetic control, and diabetic experimental and non-diabetic experimental groups (5 mice each group). Diabetic and non-diabetic experimental groups treated with 3 × 107 CFU mL-1 L. delbrueckii subsp. lactis PTCC1057 by gavage feeding approach daily for 28 days. Serum glucose, fetuin-A, and sestrin 3 levels were measured by standard methods. The result showed that oral administration of L. delbrueckii significantly decreased serum glucose in comparison to diabetic control group (P = 0.01). Serum fetuin-A level was higher in diabetic control group than non-diabetic group and oral administration of L. delbrueckii subsp. lactis PTCC1057 significantly decreased fetuin-A level in diabetic experimental group in comparison with non-diabetic groups (P = 0.001). Sestrin 3 level significantly was lower in diabetic control group than non-diabetic control group (P = 0.03) and it significantly increased in diabetic experimental group in comparison with diabetic control group after intervention of L. delbrueckii subsp. lactis PTCC1057 (P = 0.02). The results show that feeding the STZ-induced diabetic mice with L. delbrueckii subsp. lactis PTCC1057 terminated to decrease in fasting blood glucose and fetuin-A level and increase in serum sestrin 3 level. Therefore, the L. delbrueckii subsp. lactis PTCC1057 can be considered as excellent candidate for future studies on diabetes mellitus.

Nanocellulose-based Delivery Systems and Cervical Cancer: Review of the Literature.

It has become clear that targeted therapy is one of the best options for decreasing the unpleasant side effects of existing common methods and reducing the number of deaths occurred due to many types of cancer. Biocompatible and non-toxic delivery systems are provided by nanomedicine for aiding targeted therapy in many diseases containing cancer. Cervical cancer (CC) is not only the most common gynecological cancer but also is ranked as the fourth common cancer between both men and women. Chemotherapy, radiotherapy, surgery, and immunotherapy are the approaches, which are being used for treating CC patients. However, more efficacy of these methods can be achieved with the help of nanomedicine and novel delivery systems. Nanocellulose is one of the agents used for designing these systems in order to deliver different drugs to a diversity of cancerous cells. In this review, we aim to investigate the competency of nanocellulose for establishing novel therapeutic methods for cervical cancer. We hope that our results help develop more drug delivery systems for targeted therapy to reduce the side effects and induce the efficacy of anti-cancer drugs.

Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer.

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.