Ameliorative effect of licorice extract against the detrimental effect of glyphosate-based pesticide: Toxicity and health.

This study sheds the light on the potential of licorice (Glycyrrhiza glabra) root aqueous extract as a cornerstone for mitigating and detoxifying the residues of the widely used agricultural Glyphosate-based pesticides (GBPs). This study examined the GBPs toxic effects on kidney, liver, thyroid functions, and apoptosis using 50 adult male albino rats. All rats were divided into 5 groups, with 10 each. Control: served as untreated rats. GBP: rats were treated with 1 mL glyphosate solution 24 % orally for three weeks. The glyphosate-treated rats were gavaged with licorice root aqueous extractsolution (100, 200, and 300 mg/mLdistilled water, respectively) daily for three weeks. Licorice root aqueous extract solution (300 mg/mL distilled water) yielded notable reductions in liver, kidney enzymes, albumin, and AFP levels within the serum. Immunological tests, including immunohistochemical evaluations of caspase-3 and TNF-α expressions revealed a dose-dependent attenuation of apoptosis and inflammation with licorice intervention. This will provide a valuable perspective for agricultural practices future and paving the way for a more sustainable approach for using GBPs in animal agriculture industries.

Design, synthesis and molecular docking study of new pyrimidine-based hydrazones with selective anti-proliferative activity against MCF-7 and MDA-MB-231 human breast cancer cell lines.

Efforts were directed on the design, synthesis and evaluation of the anticancer activity of some pyrimidine-based hydrazones against two breast cancer cell lines, MCF-7 and MDA-MB-231. Preliminary screening results revealed that some candidates scrutinized for their antiproliferative activities exhibited IC50 values of 0.87 µM-12.91 µM in MCF-7 and 1.75 µM-9.46 µM in MDA-MB-231 cells, indicating almost equal activities on both cell lines and better growth inhibition activities than those of the positive control 5-fluorouracil (5-FU) which displayed IC50 values of 17.02 µM and 11.73 µM respectively. Selectivity of the significantly active compounds was estimated against MCF-10A normal breast cells when compounds 7c, 8b, 9a and 10b exhibited superior activity for cancerous cells than for normal cells when compound 10b presented the best selectivity Index (SI) with respect to both MCF-7 and MDA-MB-231 cancer cells in comparison to the reference drug 5-FU. Mechanisms of their actions were explored by inspecting activation of caspase-9, annexin V staining and cell cycle analysis. It was noticed that compounds 7c, 8b, 8c 9a-c and 10b produced an increase in caspase-9 levels in MCF-7 treated cells with 10b inducing the highest elevation (27.13 ± 0.54 ng/mL) attaining 8.26-fold when compared to control MCF-7 which was higher than that of staurosporine (19.011 ± 0.40 ng/mL). The same compounds boosted caspase-9 levels in MDA-MB-231 treated cells when an increase in caspase-9 concentration reaching 20.40 ± 0.46 ng/mL (4.11-fold increase) was observed for compound 9a. We also investigated the role of these compounds for their increasing apoptosis ability against the 2 cell lines. Compounds 7c, 8b and 10b tested on MCF-7 cells displayed pre-G1 apoptosis and arrested cell cycle in particular at the S and G1 phases. Further clarification of their effects was made by modulating their related activities as inhibitors of ARO and EGFR enzymes when 8c and 9b showed 52.4% and 58.9% inhibition activity relative to letrozole respectively and 9b and 10b showed 36% and 39% inhibition activity of erlotinib. Also, the inhibition activity was verified by docking into the chosen enzymes.

Quercetin potentiates 5-fluorouracil effects in human colon cancer cells through targeting the Wnt/ß-catenin signalling pathway: the role of miR-27a.

Introduction: 5-fluorouracil (5-FU) is the most widely used chemotherapeutic drug in treating colorectal cancer. However, its toxicity to normal tissues and tumour resistance are the main hurdles to efficient cancer treatment. MiR27-a promotes the proliferation of colon cancer cells by stimulating the Wnt/ß-catenin pathway. The present study was conducted to examine whether quercetin (Q) combined with 5-FU improves the anti-proliferative effect of 5-FU on HCT-116 and Caco-2 cell lines through detection of the miR-27a/Wnt/ß-catenin signalling pathway. Material and methods: Cell viability in HCT-116 and Caco-2 cell lines following quercetin and 5-FU treatment alone and in combination for 48 hours was determined using the MTT assay. The flow cytometry, quantitative real-time polymerase chain reaction, and ELISA techniques were used. Results: Our results showed that combination of quercetin and 5-FU exhibited greater cytotoxic efficacy than did 5-FU alone. Co-administration of both drugs either in combination 1 (1 : 1 Q: 5-FU) or in combination 2 (1 : 0.5 Q: 5-FU) enhanced apoptosis in HCT-116 and Caco-2 cells compared with 5-FU alone and significantly inhibited the expression of miR-27a, leading to upregulation of secreted frizzled-related protein 1 and suppression of Wnt/ß-catenin signalling, which was confirmed by a significant decrease in cyclin D1 expression. Conclusions: Quercetin strongly enhanced 5-FU sensitivity via suppression of the miR-27a/Wnt/ß-catenin signalling pathway in CRC, which advocates further research of this combination with the lower dose of 5-FU.

Insights into HPLC-MS/MS Analysis, Antioxidant and Cytotoxic Activity of Astragalus fruticosus against Different Types of Cancer Cell Lines.

Plants from the genus Astragalus are gaining attention for their pharmacological importance. However, the information available regarding the HPLC-MS/MS chemical profile of A. fruticosus is inadequate. In this study, we performed HPLC-MS/MS analysis using electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). We tentatively identified 11 compounds in the A. fruticosus methanolic extract, including five flavonoidal and six saponin glycosides. The extract showed moderate antioxidant activity with 21.05% reduction in DPPH UV absorption. The preliminary cytotoxic screening against seven human cancer cell lines using 100 µg/mL extract showed prominent cytotoxic potential against colorectal cancer HCT-116 with 3.368% cell viability. It also showed moderate cytotoxic potential against prostate (DU-145), ovarian (SKOV-3) and lung (A-549) cancer cell lines with cell viability of 14.25%, 16.02% and 27.24%, respectively. The IC50 of the total extract against HCT-116 and DU-145 cell lines were 7.81 µg/mL and 40.79 µg/mL, respectively. The observed cytotoxicity of the total methanolic extract from the leaves against colorectal cancer might facilitate future investigations on cytotoxic agent(s) for disease management.

A Novel Role of Galectin-3 and Thyroglobulin in Prognosis and Differentiation of Different Stages of Thyroid Cancer and Elucidation of the Potential Contribution of Bcl-2, IL-8 and TNF-α.

Thyroid cancer is among the most prevalent cancers with different types and stages. New markers are required for the prognosis and diagnosis of the disease. The present study aimed to detect the role of new markers, including galectin-3 (Gal-3) and thyroglobulin (TG), in the prognosis and staging of thyroid cancer. The study also investigated the potential apoptotic and inflammatory mechanisms involved in thyroid cancer through the determination of B-cell lymphoma 2 (Bcl-2), interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) during the different stages of the cancer using a series of molecular methods. Histopathological and immunohistochemical examinations were also performed. A total of 300 subjects were classified into: 100 normal healthy subjects matched in age and sex, 100 patients with thyroid carcinoma stage I (T1N0M0) and 100 patients with thyroid carcinoma stage 2 (T2N1M1). Interestingly, the present study revealed a significant increase in the levels of TG and Gal-3 in thyroid cancer patients compared to the control group. Furthermore, the levels of Bcl-2, IL-8 and TNF-α significantly increased in the patient serum. The histopathological examination and immunohistochemical observations confirmed the molecular and hematological findings. Collectively, the present study concluded that serum TG and Gal-3 could be useful markers in the prognosis and staging of patients with thyroid cancer. Furthermore, the determination of Bax, Bcl-2, IL-8 and TNF-α levels constitute a major important marker for investigation of the mechanisms of apoptosis and inflammation in thyroid cancer. To our knowledge, this is the first study that used both galectin-3 and TG as tumor markers in the prognosis and differentiation between the different stages of cancer.

Baicalin; a promising chemopreventive agent, enhances the antitumor effect of 5-FU against breast cancer and inhibits tumor growth and angiogenesis in Ehrlich solid tumor.

Despite considerable advances in cancer treatment, chemotherapy remains a cornerstone in breast cancer therapy. Therefore, reducing chemoresistance and adverse effects of chemotherapy is a priority. In this regard, Baicalin (BA) is the dominant natural flavonoid extracted from the roots of Scutellaria baicalensis showed fascinating antitumor activity in many types of cancers, including breast cancer. The present study aimed to explore the chemopreventive and antitumor action of baicalin alone and in combination with 5-FU in addition to its ability to enhance the antitumor effect of 5-FU on breast cancer using the Ehrlich solid tumor-mice model. MATERIALS AND METHODS: A total of 70 female mice were divided into seven groups (1st group, saline group; 2nd group, DMSO group; 3rd group, BA+EST group; 4th group, EST group; 5th group, EST+5-FU; 6th group, EST+BA group; 7th group, EST+5-FU+BA).tumors were assessed by weight and histopathological examination. Inflammation, angiogenesis, and apoptosis were examined by ELISA, qRT-PCR, and immunohistochemical examinations. RESULTS: showed that pre-treatment with baicalin and treatment with baicalin and/or 5-FU significantly reduced inflammation and angiogenesis indicated by suppression of NF-kB/ IL-1ß and VEGF amplification loop with marked elevation in apoptosis indicated by up-regulation of apoptotic caspase-3, pro-apoptotic p53, Bax and downregulation of anti-apoptotic Bcl-2. CONCLUSION: BA is a promising preventive or adjuvant therapy in breast cancer treatment with 5-FU mainly via cooperative inhibition of inflammation, angiogenesis, and triggering apoptotic cell death.

The influence of vinpocetine alone or in combination with Epigallocatechin-3-gallate, Coenzyme COQ10, Vitamin E and Selenium as a potential neuroprotective combination against aluminium-induced Alzheimer's disease in Wistar Albino Rats.

Alzheimer's disease (AD) is one of such diseases that represent the most prominent cause of dementia in elderly people. To explore the possible neuroprotective effect as well as mechanism of action of Vinpocetine either alone or in combination with EGCG, CoQ10, or VE & Se in ameliorating aluminum chloride-induced AD in rats. Rats were received AlCl3 (70 mg/kg) intraperitoneal daily dose for 30 days along with EGCG (10 mg/kg, I.P), CoQ10 (200 mg/kg, P.O), VE (100 mg/kg, P.O) & Se (1 mg/kg, P.O) as well as Vinpocetine (20 mg/kg, P.O) either alone or in combination. Results revealed that the combination of Vinpocetine with EGCG showed the best neuroprotection. This protection in the brain was indicated by the significant decrease in Aß and ACHE. The same pattern of results were shown in the levels of monoamines and BDNF. In addition, the combination of Vinpocetine with EGCG showed more pronounced anti-inflammatory (TNF-α, IL-1ß) and antioxidant (MDA, SOD, TAC) effects in comparison to other combinations. These results were confirmed using histopathological examinations as well as DNA fragmentation assays. Vinpocetine with EGCG showed pronounced protection on neurons against AD induced by AlCl3 in rats.

The antitumour effect of galangin and luteolin with doxorubicin on chemically induced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC), a highly malignant tumour with very high morbidity and mortality, remains the second cause of cancer-related deaths worldwide. Galangin is a naturally occurring flavonoid extracted from the propolis and root of Alpinia officinarum, which possesses antitumour efficacy, which has resulted in an increase in interest in related research. Additionally, galangin inhibits cell proliferation and induces apoptosis in several human malignancies. On the other hand, luteolin, a naturally occurring flavonoid found in a variety of edible plants, augments cytotoxicity in different cancer cells through the inhibition of cell-survival pathways and activation of apoptosis. Moreover, luteolin blocks the activity of anti-apoptotic Bcl-2 family members. The present study aimed to assess the antitumour effect of galangin and luteolin in combination and the antitumour effect of a combination of galangin and luteolin together with doxorubicin (DOX) in a chemically induced HCC rat model. Our analyses demonstrated that the combination treatment with galangin, luteolin, and DOX showed the greatest antineoplastic activity against HCC, which was observed by significant decreases in the levels of HCC markers, including serum α-fetoprotein-L3, and hepatic tissue expression of both glypican 3 and heat shock proteins. On the other hand, the hepatic tissue expression of caspase-3 was significantly increased. These results suggest that combination treatment with galangin and luteolin is a promising candidate for clinical use in HCC chemotherapy, especially when used in combination with DOX.

Prognostic Value of Serum Thyroglobulin and Anti-Thyroglobulin Antibody in Thyroid Carcinoma Patients following Thyroidectomy.

Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.

Phytic acid potentiates oxaliplatin effects in colorectal cancer induced by 1,2-DMH: the role of miR-224 and miR-200a.

INTRODUCTION: The third most frequently diagnosed cancer and one of the highest causes of tumour deaths worldwide is colorectal cancer (CRC). The main objective of this study was to determine the role of microRNA-224 (miR-224) as well as microRNA-200a (miR-200a) in CRC. Phytic acid (PA) is a natural antitumour product that was reported to inhibit CRC and play a vital role as a chemopreventive agent against CRC. MATERIAL AND METHODS: We induced CRC in albino rats using 1,2-dimethylhydrazine (1,2-DMH). The miR-224, miR-200a, and ß-catenin expressions were determined. ELISAs were performed to investigate Bcl-2 expression, caspase-3 activity, and total tissue antioxidants. Finally, histopathological investigations were performed. RESULTS: We observed a chemoprotective role of PA. PA has a synergistic effect as an antitumour agent with oxaliplatin in CRC treatment. The miR-224, miR-200a, and ß-catenin expression, when treated with PA alone or with oxaliplatin, was decreased markedly in comparison with the positive control group. The histopathological investigations of colorectal tissues confirmed our molecular and biochemical findings. CONCLUSIONS: Phytic acid possessed efficient anti-carcinogenic properties alone or with oxaliplatin against 1,2-DMH-induced CRC in rats through pathways of apoptosis, cell proliferation, and antioxidants.

Design and Optimization of Orally Administered Luteolin Nanoethosomes to Enhance Its Anti-Tumor Activity against Hepatocellular Carcinoma.

Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.

Association between serum soluble Toll-like receptor 2 and 4 and the risk of breast cancer.

Soluble Toll-like receptor (sTLR) 2 and 4 are endogenous negative regulators of TLR2 and TLR4 signaling. Therefore, the present study aimed to determine the serum levels of sTLR2 and 4, and to investigate the association between their levels and the clinicopathological parameters of patients with breast cancer. A total of 100 female patients with breast cancer (50 non-metastatic and 50 metastatic), as well as 50 healthy control volunteers were enrolled in the present study, and serum levels of sTLR2 and 4 were determined by ELISA. A significant increase in serum sTLR2 was detected in patients with non-metastatic (2,258.2±1,832.44 pg/ml) and metastatic (5,997.4±8,585.23 pg/ml) breast cancer, compared with the control group (1,106.8± 99.93 pg/ml; P=0.0001). A significant increase in serum sTLR4 was also detected in patients with both non-metastatic (1,945.2±1,709.53 pg/ml) and metastatic breast cancer (7,800.1±13,041.28 pg/ml), compared with the control group (1,106.8±108.32 pg/ml; P=0.0001). Furthermore, a positive correlation was observed between the levels of serum sTLR4 and 2 and clinicopathological parameters, such as progesterone receptor and estrogen receptor expression. In conclusion, sTLR2 and sTLR4 may be potential biomarkers of breast cancer susceptibility.

Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2-dimethylhydrazine in rats.

Several studies have revealed that the combination of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), and vitamin D reduces the risk of common types of cancers. Nonetheless, research on the deal concentrations used to test the impact of vitamin D on colon cancer is deficient. Along these lines, the aim of the present study was to evaluate the possible role of indomethacin and vitamin D as a preventative as well as a therapeutic operator for colon cancer growth induced by dimethylhydrazine (DMH) in male Albino rats. Fifty male albino rats were utilized in this examination; five groups were assigned from the animals (10 animals each): i) control group considered healthy animals; ii) carcinogen group that received DMH only; iii) prophylactic group; iv) vitamin D and indomethacin-treated group; and v) 5-flurouracil (5-FU) group. Western blot technique was used to determine the expression of carcinoembryonic antigen (CEA) and platelet-derived growth factor (PDGF). Overexpression of CEA and PDGF was noted in the carcinogenic group, while expression of CEA and PDGF in the prophylactic, vitamin D and indomethacin and 5-FU groups were markedly reduced. There was a likewise decline in tissue caspase-3 activity and antioxidant parameters in the carcinogenic group, while, there was an increase in these markers in the 5-FU group as well as the prophylactic and vitamin D and indomethacin groups. The combination of vitamin D and indomethacin markedly reduced the incidence and severity of colon cancer. The molecular, biochemical and histopathological analysis related with the oral administration of vitamin D and indomethacin display its capacity to limit the frequency of colorectal cancer.

Serum soluble toll-like receptor 2 and 4 as diagnostic and prognostic biomarkers for non-Hodgkin lymphoma.

AIM OF THE STUDY: To assess the serum levels of soluble toll-like receptor 2 (sTLR2) and soluble toll-like receptor 4 (sTLR4) in a group of patients with non-Hodgkin lymphoma (NHL) and to investigate their correlations with the clinicopathological parameters of NHL. MATERIAL AND METHODS: Fifty patients with early-stage NHL and 50 patients with advanced-stage NHL along with 50 age- and sex-matched healthy volunteers were enrolled in the study. Serum levels of sTLR2 and sTLR4 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: A significant increase in the serum levels of sTLR2 (pg/ml) was detected in early stage NHL (group I) (2381.1 ±1822.0) and advanced stage NHL (group II) (2864.9 ±2599.9) when compared to levels in the control group (1229.2 ±70.55) (p < 0.001). A significant increase in the serum levels of sTLR4 (pg/ml) was detected in early stage NHL (2465.4 ±3501.8) and advanced stage NHL (4759.7 ±5176.2) when compared to levels in the control group (1242.3 ±53) (p < 0.001). A significant positive correlation was detected between the serum levels of both sTLR2 and sSTLR4 and the Ann Arbor staging of NHL. CONCLUSIONS: sTLR2 and sTLR4 might be diagnostic and prognostic biomarkers for NHL.

Serum soluble Toll-like receptor 4 and the risk of hepatocellular carcinoma in hepatitis C virus patients.

INTRODUCTION: Soluble Toll-like receptor 4 (sTLR4) is a negative regulator of TLR4 signalling that has been reported in different diseases. In this study, we aimed to assess the serum levels of sTLR4 in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the correlation of sTLR4 with clinicopathological and biochemical parameters among HCV-related HCC patients and hepatitis C without HCC patients. MATERIAL AND METHODS: Fifty patients with HCV-related HCC, 50 patients with hepatitis C without HCC and 50 healthy control volunteers were enrolled. Clinicopathological and biochemical parameters were examined in all patients. Serum levels of sTLR4 were measured using enzyme-linked immunosorbent assay. RESULTS: A significant increase in serum sTLR4 was detected in patients with HCV-related HCC (4436.1 ±7089.8) (pg/ml) ± compared to the level in patients with hepatitis C without HCC (1561.4 ±532.0) (pg/ml) (p = 0.002) and the level in the control group (1170.38 ±159.42) (pg/ml) (p < 0.001). Serum sTLR4 was positively correlated with serum AST activity, serum direct bilirubin levels, serum alpha fetoprotein levels, tumour stages of HCC according to the Barcelona Clinic Liver Cancer staging system (BCLC), and the severity of liver cirrhosis according to the Child-Pugh classification among the patients with HCV-related HCC. The combination of serum alpha fetoprotein and serum sTLR4 increased the sensitivity of HCC detection to 76% and the specificity to 94%. CONCLUSIONS: Serum sTLR4 may be a marker for HCC susceptibility among HCV-infected patients.