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Microscopic examination using H & E. A: Papillary hyperplasia with mild dysplasia in the cancer-induced group. B: Papillary hyperplasia without any dysplasia in the cancer-prevented group. C: GI papillary transition cell carcinoma infiltrating lamina propria in cancer-induced group. D: Proliferative lesion formation (Brunn's nests) in the cancerprevented group. E: Marked mucosal dysplasia along whole mucosal thickness and mild edema in lamina propria of cancer-induced group. F: Increased mucosal thickness with small focus of squamous metaplasia (intercellular desmosomes) in the cancer-prevented group.

Microscopic examination using H & E. A: Papillary hyperplasia with mild dysplasia in the cancer-induced group. B: Papillary hyperplasia without any dysplasia in the cancer-prevented group. C: GI papillary transition cell carcinoma infiltrating lamina propria in cancer-induced group. D: Proliferative lesion formation (Brunn's nests) in the cancerprevented group. E: Marked mucosal dysplasia along whole mucosal thickness and mild edema in lamina propria of cancer-induced group. F: Increased mucosal thickness with small focus of squamous metaplasia (intercellular desmosomes) in the cancer-prevented group.

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Objectives: Pomegranate juice (PJ) is rich in important compounds with anti-cancer activities. This study aims to investigate the preventive effect of pomegranate juice (PJ) against bladder cancer (BC). Methods: Eighty male Sprague Dawley rats were randomly classified into 4 equal groups: (1) Normal controls; (2) PJ group: supplied by PJ for 12...

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... histological examination of rats of the cancer-prevented group didn't exhibit neoplastic bladder lesions. Mild preneoplastic alterations were observed in 5 cases of this group (25%) including mucosal thickness and dysplasia, inflammation and capillary congestion ( Figure 2). The bladders of control and PJ groups exhibited negative p53 immunostaining (grade 0 intensity). ...
Context 2
... of PJ in our study reduced expression of mutant TP53 gene among cancer-prevented group, therefore supporting the apoptotic and anticancer effects of PJ. The pro-apoptosis and anti-proliferative effects of pomegranate on BC cells might be due to regulation of p53/miR-34a axis (Zhou et al., 2015). p1: Normal vs PJ vs cancer-induced vs cancer-prevented groups. ...

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... Furthermore, the detected apoptotic effect of PJC was enhanced dose-dependently, as indicated in Figure 9B, in which the nuclei of PI-stained HepG-2 cells became more condensed with chromatin fragmentation with the increase in PJC concentration compared to untreated HepG-2 cells (control). The dose-dependency of pomegranate fruit extract to inhibit bladder cancer development was also previously reported [49] and attributed to its anti-inflammatory and antioxidant potentials. Moreover, the cell cycle division profile of the PJC-treated HepG-2 cells was analyzed to confirm its apoptotic mechanism, which showed an enhancement in cell cycle arrest ( Figure 9C). ...
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Pomegranate juice concentrate (PJC) is a rich source of polyphenols, which exhibit significant antioxidant activity and potential health benefits for disease prevention and therapy. In this study, the polyphenolic profile of PJC was investigated for the first time, and it was found that PJC can inhibit oxidative damage to bovine serum albumin (BSA) and deoxyribonucleic acid (DNA), as well as acetylcholinesterase, α-amylase, and tyrosinase activities. The primary polyphenols identified in PJC were 4-Hydroxy-3-Methoxybenzoate, epicatechin, catechin, rutin, ferulic acid, P-coumaric acid, and cinnamic acid. Additionally, PJC demonstrated potent antibacterial effects against human pathogens such as Streptococcus mutans and Aeromonas hydrophila and dose-dependently reduced the proliferation of colorectal, breast, and hepatic cancer cells via apoptosis. Furthermore, PJC blocked B-cell lymphoma 2 (BCl-2) and the expression of a potent cyclin-dependent kinase inhibitor (P21) and enhanced tumor protein (P53) expression, compared to both untreated cells and cells treated with fluoropyrimidine 5-fluorouracil (5-FU). As a result, PJC may be a beneficial ingredient in the formulation of emerging natural-compound-based chemotherapy and functional foods and could be utilized by the food, nutraceutical, and pharmaceutical industries.
... Literature survey displayed that pomegranate has potent health effects. It can prevent and assist treatment of many disorders including hyperglycemia [23], hypertension [24], hyperlipidemia [25], inflammatory diseases [26], arthritis [27], Alzheimer's disease [28], and malignancies [29][30][31]. Pomegranate extract also has antimicrobial [32], antimalarial [33], and dental antiplaque effects [34] and improves wound healing [35]. Recent studies suggested that pomegranate is effective against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections [36,37]. ...
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To investigate the effect of pomegranate juice (PJ) on the cyclosporine (CsA)-induced nephrotoxicity in rats, 80 rats were divided into four groups. The first group was regarded a negative control group, and the others were as follows: group 2 (CsA group) received CsA in a dose of 25 mg/kg/day orally, group 3 (treated group) received CsA in a dose of 25 mg/kg/day plus 2.5 mL/day of PJ, and group 4 (PJ group) received 2.5 mL of PJ daily. By the end of the 21st day, plasma creatinine, blood urea nitrogen (BUN), creatinine clearance, urinary KIM-1, and NGAL were determined. Histopathological investigation and the determination of malondialdehyde and antioxidant enzymes were analyzed in kidney tissues. The results show that plasma creatinine, BUN, creatinine clearance, and kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were significantly altered in the CsA group. The supplement of PJ attenuated the alteration in these parameters. The treatment with PJ also prohibits the CsA-induced alteration in the histopathology, lipid peroxidation, and antioxidant enzymes. We can conclude that PJ protects against CsA-induced nephrotoxicity due to its antioxidant effects.
... The experimental animals were kept under observation for seven days before start of the experiment for adaptation and fed on basal diet. Rats were divided into five groups (5 rats each), the first group (G1) rats were fed on basal diet only and contrived as normal control group (-ve), then, about Azoxymethane (AOM) was administered dissolved in 0.9% NaCl, applied subcutaneously for 2 weeks at a dose of 20 mg/kg/week until the rats became colon cancer (Mario et al., 2014) and treated with fluorouracil(5-FU)(12.5 mg/kg on days 1, 3, and 5 with a repeat cycle every 4 weeks for 4 months (Yasmin et al ., 2019).Rats were divided into four groups as follows:Group( 2) was fed by basaldiet only without treated and was designated as control positive groups(+ve).Group (3): rats injected with 5-fluorouracil (12.5 mg/kg on days 1, 3, and 5 with a repeat cycle every 4 weeks for 4 months (Yasmin et al ., 2019 ).Group(4):rats injected with (5-FU) and fed on (2.5 mL kg/day, by oral gavage) of pomegranate juice (Wael et al.,2020). Group(5):rats injected with (5-FU) andfed on (1.5 ml kg/day, by oral gavage) of pomegranate peel water extract. ...
... Likewise, phytochemicals present in pomegranate may play a significant role in modulating inflammatory cell signaling in colon cancer. Mortada et al., (2020) reported the effect against N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder cancer, attributed to that pomegranate juice can inhibit BBNinduced bladder cancer by suppressing angiogenesis, as oral intake of pomegranate juice restores oxidative stress and acts as a free radical scavenger. Prostate cancer cells also show suggestive evidence of reduction, as inhibition of cancer cells in adults widely recognized in human clinical trials. ...
Article
Background Pomegranate (Punica granatum L.) is a fruit native to South Asia, and currently can grown in tropical and subtropical areas, including Mexico, which produces approximately seven thousand metric tons per year. Pomegranate stands out for its rich flavor and functional properties, which is why it has gained acceptance in different countries in the marketing of assorted products such as jellies, jams, drinks, and its effectiveness against diseases and pathogenic microorganisms. Scope and approach This review summarizes information about the bioactive compounds of pomegranate and its nutritional properties as functional food, with emphasis on its by-products (aril, seed, and peel). Punica granatum contains bioactive compounds, the peel has a higher content of these compounds and in vitro biological properties reported by different authors. Key findings and conclusions Pomegranate and its by-products have functional properties, such as antimicrobial, anticancer, and antiviral, even against SARS COV-2 virus in vitro studies; activities attributed to punicalagin, punicalin, ellagic acid, punicic acid, and anthocyanins. It is important to further analyze this fruit's functional and nutritional effects, especially the peel. To study the mechanisms involved, to develop industrial processes for the development of a nutraceutical or functional food product.
... The next in vivo study confirmed the beneficial effect of pomegranate juice in reducing hyperplasia, dysplasia, and invasive neoplasms in the chemically induced (N-butyl-N-(4hydroxybutyl)-nitrosamine) BC rat model [69]. Rats with chemically induced BC were characterized by p53 expression impairment, while pomegranate juice treatment restored a regular p53 expression. ...
... In contrast, catalase, glutathione, and superoxide dismutase levels lowered in the cancer-induced group compared to control rats. However, pomegranate juice oral administration restored the normal status of oxidative stress markers [69]. Thus, the anticancer activity of pomegranate juice is also due to its high antioxidant activity [70]. ...
... Therefore, the use of pomegranate juice is preferable to its ingredients separately. Mortada and colleagues also demonstrated the anti-inflammatory activity of pomegranate juice [69]. Rats with chemically induced BC were characterized by increased expression of IL-6 (interleukin 6), TNF-α (tumor necrosis factor-alpha), and HIF-1 (hypoxia-inducible factor-1) in bladder tissues [69]. ...
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Bladder cancer (BC) is the most common tumor of the urinary system in the world. Moreover, despite using anticancer therapies, BC is also characterized by a high recurrence risk. Among numerous risk factors, cigarette smoking, occupational exposure to certain aromatic compounds, and genetic factors contribute most strongly to BC development. However, the epidemiological data to date suggests that diet quality may influence some carcinogenic factors of BC and, therefore, might have a preventative effect. Adequate consumption of selected fruits with scientifically proven properties, including pomegranates and cranberries, can significantly reduce the risk of developing BC, even in those at risk. Therefore, in this article, we aim to elucidate, using available literature, the role of fruits, including pomegranates, cranberries, citrus fruits, cactus pears, and apples, in BC prevention and treatment. Previous data indicate the role of compounds in the above-mentioned fruits in the modulation of the signaling pathways, including cell proliferation, cell growth, cell survival, and cell death.
... To date, there are more than 88 research studies and reports in the PubMed database that are linking pomegranate to cancer. Such research accumulation is attributable to the encouraging anticancer properties of pomegranate juice and its derived compounds [71]. In fact, pomegranate juice has been suggested to be a promising chemoprotective and/or chemotherapeutic agent against various types of cancer, mainly prostate [72][73][74][75], skin [76,77], colon [78][79][80], breast [81][82][83][84], and lung cancer [20]. ...
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Rather than the prophylactic vaccination, any effective synthetic, natural, or nutritional therapy or regimen that may cure or remedy, albeit partially, the complications of SARS-CoV-2 should be highly acknowledged. Here, we reviewed and discussed possible beneficial biological effects of pomegranate juice in such diseased condition of viral infection based on the current published evidence (direct and indirect) and owing to the robust evidence that fresh pomegranate juice is highly rich with unique bioactive compounds that are approved in various occasions to be effective in several chronic diseased conditions. All related references that serve our aim are accessed through available electronic databases, particularly PubMed and Scopus. In summary, there is accepted evidence that pomegranate juice may be beneficial in SARS-CoV-2 infection conditions, especially for patients with the clinical history of chronic diseases such as hypertension, cardiovascular disease, diabetes, and cancer. However, the interventional studies that directly probe and confirm the effectiveness of fresh pomegranate juice in the management of SARS-CoV-2 infection are mandatory.
... The PCR cycle parameters are adapted on the basis of the next programmer: pre-denaturation step for 10 min at 95 °C, 40 cycles in denaturation step for 15 s at 95 °C, annealing step for 1 min at 60 °C and finally, extension for 1 min at 72 °C. The relative quantification was calculated using equation RQ = 2 −ΔΔCT [22]. ...
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Background Toxic metals are associated with cancer progression. Studies have reported the relation between some toxic metals and renal cell carcinoma (RCC).Methods and resultsBlood levels of Cd and Pb were determined in 94 RCC patients (RCC group) and 91 matched controls as well as blood level of malondialdehyde (MDA) and catalase (CAT) activity as markers of oxidative stress and antioxidant, respectively. Gene expression of MAP kinase pathway (P38 and JNK), hypoxia-inducible factor 1-alpha (HIF1α), vascular endothelial growth factor (VEGF), cytochrome C oxidase subunit 6 (COX6), metallothionein (MT2A), and heat shock protein (HSP90AA1) were evaluated in the obtained tissue specimens. Blood Cd and Pb levels were significantly higher in RCC group comparing to control group with preferential significant increase of Cd in chromophobe RCC (chRCC) sub-type. MDA level was significantly higher and CAT activity was lower in the RCC compared to controls. The difference was evident only in chRCC. The expressions of genes were significantly increased in the cancer tissues than in non-cancerous tissues in RCC sub-types and there was a significant correlation between Cd levels and expression of genes VEGF, MT2A, P38 and JNK in chRCC group. Immunohistochemical staining of clear cell RCC tissues shows a marked expression of VEGF and HIF-1α.While COX6 staining show marked expression in chRCC.Conclusions There is a positive correlation between Cd toxicity and the development of RCC, especially chRCC sub-type. Cd is strongly incriminated in the pathogenesis of chRCC through the effort on some genes and oxidative stress markers.
Article
Bladder cancer (BC) is one of the most common malignant tumors worldwide and poses a significant hazard to human health. During the development of BC, hypoxia plays a crucial role. Hypoxia-inducible factor (HIF) is a key transcription factor for hypoxic adaptation, which regulates the transcription of various genes, including inflammation, angiogenesis, and glycolytic metabolism. Recent studies have shown the precise role of HIF in various biological behaviors of BC. More importantly, a new antitumor medication targeting HIF-2 has been used to treat renal cancer. However, therapies targeting HIF-1 in BC have not yet been developed. In this review, we discussed how HIF-1 is expressed and affects the growth, metastasis, and angiogenesis of BC. At the same time, we investigated several HIF-1 inhibitors that provide new perspectives for targeting HIF-1.
Chapter
Juices are processed from several fruits and vegetables, which are excellent sources of bioactive compounds. One of the key importance of bioactive compounds comes from their health-promoting effects, which depend not only on content but also on their bioaccessibility. A sequence of operations is involved in juice production to prepare to serve and obtain desired quality and safety. Despite the negative impact of processing steps, the favourable alterations in bioactive compounds such as polyphenols, carotenoids, vitamins and others have been shown in several studies. In addition to clarification, fermentation and enzyme treatment, many studies focus on nonthermal strategies, including ultrasound, pulsed electric field and high hydrostatic pressure as an alternative to thermal processes. In contrast with a considerable number of studies, differences in findings were reported with the content and bioaccessibility of bioactive compounds based on the treatment, conditions and food matrices. Therefore, in this chapter, evaluation and discussion of the effect of several processing steps on bioactive compounds available in juices were considered.KeywordsPolyphenolsCarotenoidsVitaminsMineralsBioaccessibility