Astaxanthin as an Anticancer Agent against Breast Cancer: An In Vivo and In Vitro Investigation.

AIM: This study aimed to investigate the antioxidant properties, cytotoxic activity, and apoptotic effects of astaxanthin (ASX) on genes and pathways involved in breast cancer in Balb/c mice models injected with the 4T1 cell line. BACKGROUND: ASX could inhibit some tumor progression by using in vivo and in vitro models. OBJECTIVE: The effect of ASX on breast cancer was not fully understood till now. METHOD: In an in vivo model, 4T1 cells-injected mice were administered with different concentrations of ASX (100 and 200 mg/kg), and histopathological evaluations were done using an optical microscope and the hematoxylin and eosin (H&E) staining. The real- time PCR investigated the expression levels of B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Caspase 3 genes in mice treated with 100 and 200 mg/kg ASX. Also, the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined in ASX-treated cancer mice. RESULTS: ASX (200 mg/kg) caused a significant reduction in the mitotic cell count of tumor tissues compared to ASX (100 mg/kg). The antiproliferative effects of different concentrations of ASX were shown based on the MTT results. The treatment of breast tumor mice with both concentrations of ASX, especially 200 mg/kg, elevated the expression of Caspase 3, Bax, and SOD enzyme levels and decreased Bcl-2 expression and MDA enzyme levels. CONCLUSION: ASX can be considered a promising alternative treatment for breast cancer.

Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury.

Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Application of Quercetin and its Novel Formulations in the Treatment of Malignancies of Central Nervous System: An Updated Review of Current Evidence Based on Molecular Mechanisms.

Quercetin, a naturally occurring polyphenolic compound found in abundance in vegetables and fruits, has emerged as a compelling subject of study in cancer treatment. This comprehensive review delves into the significance and originality of quercetin's multifaceted mechanisms of action, with a particular focus on its application in various brain tumors such as glioblastoma, glioma, neuroblastoma, astrocytoma, and medulloblastoma. This review scrutinizes the distinctive facets of quercetin's anti-cancer properties, highlighting its capacity to modulate intricate signaling pathways, trigger apoptosis, impede cell migration, and enhance radiosensitivity in brain tumor cells. Significantly, it synthesizes recent research findings, providing insights into potential structure-activity relationships that hold promise for developing novel quercetin derivatives with heightened effectiveness. By unraveling the unique attributes of quercetin's anti-brain tumor effects and exploring its untapped potential in combination therapies, this review contributes to a deeper comprehension of quercetin's role as a prospective candidate for advancing innovative treatments for brain cancer.

Therapeutic Effects of Berberine against Urological Cancers: Biological Potentials Based on Cellular Mechanisms.

Urological cancers, including prostate, kidney, and bladder cancer are problematic human diseases worldwide. Current strategies for the treatment of these cancers are chemotherapy, radiotherapy, surgery, or a combination of mentioned therapies. Due to the high mortality and morbidity rate of urological cancers and possible side effects of available standard treatments, searching for more effective and safe treatments is a critical issue. The beneficial properties of natural compounds, such as berberine, have been widely investigated in human diseases. Moreover, the anticancer potential of this agent has been extensively documented, especially in experimental studies. In this review, we have tried to discuss the effect of berberine against urological cancers, focusing on cellular and molecular mechanisms.

Targeting the NF-E2-related factor 2 pathway for overcoming leukemia.

Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. There are many types of leukemia that some of them occur in children and the others are more common in adults. Currently, there are many different chemotherapy agents for leukemia while chemoresistance increases the survival of the leukemic cells. One of the main reasons of chemoresistance, is a transcription factor called Nuclear factor erythroid 2-Related Factor 2 (NRF2). An increase in NRF2 expression in leukemic cells which are being treated with chemotherapy agents, can increase the survival of these cells in the presence of therapeutics. Accordingly, the inhibition of NRF2 by different methods as a cotreatment with classical chemotherapy agents, can be a promising procedure in leukemia treatment. In this study we focus on the association of NRF2 and leukemia and targeting it as a new therapeutic method in leukemia treatment.

Anticancer activity of thymoquinone against breast cancer cells: Mechanisms of action and delivery approaches.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Anti-gout and urate-lowering potentials of curcumin: A review from bench to beside.

BACKGROUND: Gouty arthritis is a complex form of inflammatory arthritis, triggered by the sedimentation of monosodium urate crystals in periarticular tissues, synovial joints, and other sites in the body. Curcumin is a natural polyphenol compound, isolated from the rhizome of the plant Curcuma longa, possessing countless physiological features, including antioxidant, anti-inflammatory, and anti-rheumatic qualities. OBJECTIVE: This study aimed to discuss the beneficial impacts of curcumin and its mechanism in treating gout disease. METHODS: Ten English and Persian databases were used to conduct a thorough literature search. Studies examining the anti-gouty arthritis effects of curcumin and meeting the inclusion criteria were included. RESULTS: According to the studies, curcumin has shown xanthine oxidase and urate transporter-1 inhibitory properties, uric acid inhibitory characteristics, and antioxidant and anti-inflammatory effects. However, some articles found no prominent reduction in uric acid levels. CONCLUSION: In this review, we emphasized the potency of curcumin and its compounds against gouty arthritis. Despite the potency, we suggest an additional well-designed evaluation of curcumin, before its therapeutic effectiveness is completely approved as an anti-gouty arthritis agent.

Oncogenic alterations of metabolism associated with resistance to chemotherapy.

Metabolic reprogramming in cancer cells is a strategy to meet high proliferation rates, invasion, and metastasis. Also, several researchers indicated that the cellular metabolism changed during the resistance to chemotherapy. Since glycolytic enzymes play a prominent role in these alterations, the ability to reduce resistance to chemotherapy drugs is promising for cancer patients. Oscillating gene expression of these enzymes was involved in the proliferation, invasion, and metastasis of cancer cells. This review discussed the roles of some glycolytic enzymes associated with cancer progression and resistance to chemotherapy in the various cancer types.

Protective effects of curcumin and its analogues via the Nrf2 pathway in metabolic syndrome.

Metabolic Syndrome (MetS) refers to a set of medical conditions including insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension. Due to these dysregulations, if not treated, MetS could increase the risk of CVA, CVD, and diabetes. As described by WHO, CVD is the leading cause of mortality in the world which motivates researchers to investigate the management of its risk factors, especially MetS. It is reported that oxidative stress secondary to the abundant generation of free radicals oxygen species (ROS) and the ensuing altered redox status play an important role as a mediator in MetS. As a result, using new antioxidant agents with higher bioavailability has been proposed as an efficient treatment. Curcumin (a polyphenol of the diarylheptanoids class), which is used as a traditional medicine for various diseases including cardiovascular diseases and diabetes, is characterized by its antioxidant properties which, at least in part, are mediated via the activation of the Nrf2/ARE signaling pathway. Nrf2 is a transcription factor that plays a key role in regulating internal defense systems and increases antioxidant levels to decrease oxidative damage and cell apoptosis. Nrf2 expression and stability are enhanced by curcumin, leading to a higher rate of Nrf2 migration to the cell nucleus to regulate ARE gene expression, thus protecting cells against oxidative stress. In this article, we provide a comprehensive review of the molecular effect of curcumin and its derivatives via Nrf2 regulation in several conditions, such as diabetes, hypertension, dyslipidemia, and obesity.

Involvement of Nrf2 signaling in lead-induced toxicity.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is used as one of the main protective factors against various pathological processes, as it regulates cells resistant to oxidation. Several studies have extensively explored the relationship between environmental exposure to heavy metals, particularly lead (Pb), and the development of various human diseases. These metals have been reported to be able to, directly and indirectly, induce the production of reactive oxygen species (ROS) and cause oxidative stress in various organs. Since Nrf2 signaling is important in maintaining redox status, it has a dual role depending on the specific biological context. On the one hand, Nrf2 provides a protective mechanism against metal-induced toxicity; on the other hand, it can induce metal-induced carcinogenesis upon prolonged exposure and activation. Therefore, the aim of this review was to summarize the latest knowledge on the functional interrelation between toxic metals, such as Pb and Nrf2 signaling.

Curcumin Combats against Gastrointestinal Cancer: A Review of Current Knowledge Regarding Epigenetics Mechanisms with a Focus on DNA Methylation.

Gastrointestinal (GI) cancers are one of the most common human malignancies and a leading cause of morbidity and mortality worldwide. One of the most prominent hallmarks of cancer and a basic trait of almost all GI malignancies is genomic/epigenomics alterations. DNA methylation is highlighted as a fundamental mechanism underlying the inactivation of several tumor-suppressor gene signaling pathways. Thus, sites of DNA methylation can be triggered for cancer therapy. Available therapeutic procedures for GI cancer show unsatisfactory efficacy, and some treatments are associated with severe side effects, including ulceration or bleeding. Therefore, it is essential to find alternative treatments. There is growing evidence indicating that some chemopreventive phytochemicals can combat cancer. One of the most systematically investigated nutraceuticals for its advantages in managing different diseases is curcumin (CUR). CUR is well known for its potent anticancer characteristics by targeting epigenetic mechanisms, with DNA methylation at the forefront. Prior investigations have indicated that CUR treatment can benefit GI cancers by controlling several signaling pathways related to oxidative stress and epigenomics pathways. The present literature displays recent evidence regarding DNA methylation alterations by CUR and its potential role in GI cancer prevention and treatment.

Overview of the miR-29 family members' function in breast cancer.

Accumulating evidence has indicated the importance of microRNAs (miRs) in the biology of human malignancies by targeting multiple signaling pathways and different Messenger RNA transcripts. Despite conflicting information and controversial roles in diverse cancers, miR-29 has been mostly characterized as a tumor suppressor in breast cancer (BC). Several signaling axes, including TIMP3/STAT1/FOXO1, GATA3-miR-29b, and EZH2-miR-29b/miR-30d-LOXL4 are controlled, at least partially, by miR-29 family members to suppress proliferation, invasion, and metastasis of BC cells. In contrast, some other studies showed that miR-29 is notably elevated in the serum/tissue of BC patients and triggers migration and metastasis by targeting various genes and transcription factors such as tristetraprolin, N-myc interactor, and ten-eleven translocation 1. This disagreement can be explained by the fact that miR-29 family members have a variety of regulatory roles depending on their environment and signaling pathways. Long non-coding RNAs also can modulate miR-29 expression in BC. We summarized recent discoveries regarding the important value of the miR-29 family in BC, focusing on the effects of miR-29 up/down-regulation in different subtypes of BC. We also explored the effects of miR-29 in BC initiation and progression, invasion, and therapy resistance.

Chrysin Effect Against Gastric Cancer: Focus on its Molecular Mechanisms.

Gastric cancer is one of the most prevalent cancers in the world. Various therapeutic modalities have been used for its treatment, but all exhibit severe side effects, establishing the need for novel approaches. Chrysin is a phytomedicine compound belonging to the flavonoid group. It is found in honey and many plants. Its antitumor effects have been documented against gastric cancer cell lines in vitro, establishing its effects are mediated via different pathways and the expression of miRNA. In this review, we summarize the available literature on chrysin and its effects on gastric cancer, focusing on the cellular mechanisms it targets.

Buprenorphine administration during gestation induces hepatotoxicity in the rat fetus.

This study investigated the effect of buprenorphine (BUP) on the livers of pups exposed to this drug during the fetal stage. BUP decreased the activities of serum liver enzymes in exposed animals versus the controls. BUP (0.5 mg/kg) decreased malondialdehyde levels and increased the glutathione levels in the liver of animals versus other groups. The superoxide dismutase activity was elevated in the BUP 0.5 mg/kg group versus the control group. BUP (1 mg/kg) induced histopathological changes in the livers of pups. In conclusion, BUP may induce hepatotoxicity in pups exposed to this drug during the fetal stage.

Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity in Rats: Biochemical and Histopathological Approaches in a Sub-chronic Study.

BACKGROUND: Chrysin (CH) is one of the important natural flavonoids with antioxidant and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos (CPF). METHODS: We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated CH at 12.5, 25, and 50 mg/kg/day for 45 days. RESULTS: In this study, CPF increased liver enzyme activities compared with the control group (p < 0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p < 0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the concentrations of MDA and NO in the CPF group was observed compared with the control group (p < 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p < 0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in the serum concentration of IL-6 compared with the control animals. No significant changes were found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration of CH plus CPF induced histopathological alterations in liver. CONCLUSION: These results suggest that CH attenuates hepatic enzymes and histopathological alterations induced by CPF via modulating oxidative stress and inflammatory indices in rats.

Mechanistic Features and Therapeutic Implications Related to the MiRNAs and Wnt Signaling Regulatory in Breast Cancer.

Breast cancer (BC) is accountable for a large number of female-related malignancies that lead to lethality worldwide. Various factors are considered in the occurrence of BC, including the deregulation of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT). Genetic factors such as microRNAs (miRs) are crucially responsible for BC progression and aggressiveness. Hence, the association of miRs and EMT regulators (e.g., Wnt signaling pathway) is of importance. In the present review, we accurately discussed this interplay (interaction between Wnt and miRs) concerning cell - invasion, -migration, -differentiation, -chemoresistance, survival, and-proliferation, and BC prognosis. The putative therapeutic agents, multidrug resistance (MDR) evade, and possible molecular targets are described as well.

A systematic review of photocatalytic degradation of humic acid in aqueous solution using nanoparticles.

OBJECTIVES: Humic acid (HA) compounds in the disinfection processes of drinking water and wastewater are considered as precursors of highly toxic, carcinogenic and mutagenic disinfectant by-products. The aim of this study was to systematically review all research studies on the photocatalytic degradation of humic acid and to evaluate the laboratory conditions and results of these studies. CONTENT: The present systematic review was performed by searching the Scopus, PubMed, and web of science databases until December 2021. The parameters of type of catalyst, catalyst size, optimum pH, optimum initial concentration of humic Acid, optimum catalyst concentration, optimum time, light used and removal efficiency were investigated. SUMMARY: 395 studies were screened and using the inclusion and exclusion criteria, in total, 20 studies met our inclusion criteria and provided the information necessary to Photocatalytic degradation of humic acid by nanoparticles. In the investigated studies, the percentage of photocatalytic degradation of humic acid by nanoparticles was reported to be above 70%, and in some studies, the removal efficiency had reached 100%. OUTLOOK: From the results of this systematic review, it was concluded that the photocatalytic process using nanoparticles has a high effect on the degradation of humic acid.

Prevalence of Metabolic Syndrome and Its Associated Potential Factors among the Elderly in the East of Iran.

BACKGROUND AND AIMS: This cross-sectional study aimed to determine potential factors with a strong association with metabolic syndrome (MetS) among obesity and lipid-related parameters, and liver enzymes, fasting blood glucose (FBG), and blood pressure (BP) as well as some sociodemographic factors in elderly over 60 years old from a sample of Birjand Longitudinal Aging Study (BLAS). METHODS: A total of 1366 elderly Birjand participants were enrolled and divided into non-MetS (n = 512) and MetS (n = 854) groups based on the status of MetS from January 2018 to October 2018. The anthropometric parameters, blood lipid profiles, liver enzymes, and disease history were evaluated and recorded. RESULTS: 62.5% of the participants from our sample of elderly Birjand have MetS (33.4% in males and 66.6% in females). The prevalence of MetS in females was significantly higher than in males (P < 0.001). The increasing trend in the number of MetS components (from 0 to 5) was observed in females (p < 0.001). Odds ratio showed a strong association between female gender [8.33 (5.88- 11.82)], obesity [8.00 (4.87-13.14)], and overweight [2.44 (1.76-3.40)] with MetS and acceptable association between TG/HDL [(1.85 (1.62-2.12)] with MetS. CONCLUSION: This study indicated that the female sex, overweight and obesity have a strong association with MetS and TG/HDL has an acceptable association found in the sample of the elderly Birjand population. However, due to the obvious limitations of our study including the homogeneous sex and race of population, and no adjustment for several important confounding factors including sex, different ages, stage in the elderly, alcohol consumption, smoking, married status, physical activity, diet, and family history of CVD, more epidemiological investigations are needed to address this question.