Cryptolepine Analog Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway.

BACKGROUND: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. OBJECTIVE: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. METHODS: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. RESULTS: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. CONCLUSION: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.

Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins.

The current study evaluated the cytotoxic activity of 11-(1,4-bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline (BAPPN), a novel derivative of 5-methyl-5H-indolo[2,3-b]quinoline, against hepatocellular carcinoma (HepG2), colon carcinoma (HCT-116), breast (MCF-7), and lung (A549) cancer cell lines and the possible molecular mechanism through which it exerts its cytotoxic activity. BAPPN was synthesized and characterized with FT-IR and NMR spectroscopy. The binding affinity scores of BAPPN for caspase-3 PDB: 7JL7 was -7.836, with an RMSD of 1.483° A. In silico screening of ADME properties indicated that BAPPN showed promising oral bioavailability records in addition to their high gastrointestinal absorption and blood-brain barrier penetrability. BAPPN induced cytotoxicity, with IC50 values of 3.3, 23, 3.1, and 9.96 µg/mL against cancer cells HepG2, HCT-116, MCF-7, and A549, respectively. In addition, it induced cell injury and morphological changes in ultracellular structure, including cellular delayed activity, vanishing of membrane blebbing, microvilli, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin autophagosomes. Furthermore, BAPPN significantly increased the protein expression of caspase-3 and tumor suppressor protein (P53). However, it significantly reduced the secretion of vascular endothelial growth factor (VEGF) protein into the medium and decreased the protein expression of proliferation cellular nuclear antigen (PCNA) and Ki67 in HepG2, HCT-116, MCF-7, and A549 cells. This study indicates that BAPPN has cytotoxic action against liver, colon, breast, and lung cancer cell lines via the up-regulation of apoptotic proteins, caspase-3 and P53, and the downregulation of proliferative proteins, VEGF, PCNA, and Ki67.

Assessment of macronutrients dietary intake, central adiposity among pre- and postmenopausal Egyptian women with benign and malignant breast tumors.

BACKGROUND: Breast cancer (BC) is the second most frequent cancer in women and the second most common cancer worldwide. Lifestyle factors, like body weight, physical activity and diet, may be accompanying with higher BC risk. AIM: The assessment of macronutrients dietary intake; protein, fat, carbohydrates and their components of amino, fatty acids, and central obesity/adiposity among pre- and postmenopausal Egyptian women with benign and malignant breast tumors. METHODS: The current case control study included 222 women: 85 control, 54 benign and 83 breast cancer patients. Clinical, anthropocentric and biomedical examinations were performed. Dietary history and health attitude were done. RESULTS: The anthropometric parameters including waist circumference (WC) and the body mass index (BMI) of the benign and the women with malignant breast lesions showed the highest values when compared to the control (35.45 ± 15.58 km2 and 101.24 ± 15.01 cm, 31.39 ± 6.77 km2 and 98.85 ± 13.53 cm and 27.51 ± 7.10 km2 and 84.33 ± 13.78 cm). The biochemical parameters revealed high concentration of the total cholesterol (TC) (192.83 ± 41.54 mg/dl), low density lipoprotein-cholesterol (LDL-C) (117.88 ± 35.18 mg/dl) and the median insulin level 13.8 (10.2-24.1) µu/ml in the malignant patients with high significant difference compared to the control. The malignant patients had the highest daily caloric intake (795.84 ± 519.95 K calories) proteins (65.39 ± 28.77 g), total fats (69.09 ± 32.15 g) and carbohydrates (196.70 ± 85.35 g), when compared to the control. Data also revealed the high daily consumption of the different types of the fatty acids with high linoleic/linoleinic ratio among the malignant group (14.284 ± 6.25). Branched chain amino acids (BGAAs), sulphur amino acids (SAAs), conditional amino acids (CAAs) and aromatic amino acids (AAAs) proved to be the highest in this group. Correlation coefficient between the risk factors revealed either positive or negative weak correlation except that between serum LDL-C concentration and the amino acids (isoleucine, valine cysteine, tryptophan and tyrosine) and negative association with the protective polyunsaturated fatty acids. CONCLUSION: Participants with breast cancer had the greatest levels of body fatness and unhealthy feeding habits relative to their high calorie, protein, carbohydrate, and fat intake.

Molluscicidal and Larvicidal Potency of N-Heterocylic Analogs against Biomophalaria alexandrina Snails and Schistosoma mansoni Larval Stages.

This work describes the synthesis of quinoline-based N--heterocyclic arenes and their biological evaluation as molluscicides against adult Biomophalaria alexandrina snails as well as larvicides against Schistosoma mansoni larvae (miracidia and cercariae). Molecular docking studies were demonstrated to investigate their affinity for cysteine protease protein as an interesting target for antiparasitics. Compound AEAN showed the best docking results followed by APAN in comparison to the co-crystallized ligand D1R reflected by their binding affinities and RMSD values. The egg production, hatchability of B. alexandrina snails and ultrastructural topography of S. mansoni cercariae using SEM were assessed. Biological evaluations (hatchability and egg-laying capacity) revealed that the quinoline hydrochloride salt CAAQ was the most effective compound against adult B. alexandrina snails, whereas the indolo-quinoline derivative APAN had the most efficiency against miracidia, and the acridinyl derivative AEAA was the most effective against cercariae and caused 100% mortality. CAAQ and AEAA were found to modulate the biological responses of B. alexandrina snails with/without S. mansoni infection and larval stages that will affect S. mansoni infection. AEAA caused deleterious morphological effects on cercariae. CAAQ caused inhibition in the number of eggs/snail/week and reduced reproductive rate to 43.8% in all the experimental groups. CAAQ and AEAA can be recommended as an effective molluscicide of plant origin for the control program of schistosomiasis.

Impact of Synthesized Indoloquinoline Analog to Isolates from Cryptolepis sanguinolenta on Tumor Growth Inhibition and Hepatotoxicity in Ehrlich Solid Tumor-Bearing Female Mice.

The study evaluated the antitumor efficacy of APAN, "synthesized indoloquinoline analog derived from the parent neocryptolepine isolated from the roots of Cryptolepis sanguinolenta", versus the chemotherapeutic drug etoposide (ETO) in Ehrlich solid tumor (EST)-bearing female mice as well as its protective effect against etoposide-triggered hepatic disorders. APAN showed an ameliorative activity against Ehrlich solid tumor and hepatic toxicity, and the greatest improvement was found in the combined treatment of APAN with ETO. The results indicated that EST altered the levels of tumor markers (AFP, CEA, and anti-dsDNA) and liver biomarker function (ALT, AST, ALP, ALB, and T. protein). Furthermore, EST elevated CD68 and anti-survivin proteins immuno-expressions in the solid tumor and liver tissue. Molecular docking studies were demonstrated to investigate their affinity for both TNF-α and topoisomerase II as target proteins, as etoposide is based on the inhibition of topoisomerase II, and TNF-α is quite highly expressed in the solid tumor and liver tissues of EST-bearing animals, which prompted the authors' interest to explore APAN affinity to its binding site. Treatment of mice bearing EST with APAN and ETO nearly regularized serum levels of the altered parameters and ameliorated the impact of EST on the tissue structure of the liver better than that by treatment with each of them separately.

Design and cytotoxic evaluation via apoptotic and antiproliferative activity for novel 11(4-aminophenylamino)neocryptolepine on hepatocellular and colorectal cancer cells.

The current study evaluated the cytotoxic activity of 11(4-Aminophenylamino)neocryptolepine (APAN), a novel derivative of neocryptolepine, on hepatocellular (HepG2) and colon (HCT-116) carcinoma cell lines as well as, the possible molecular mechanism through which it exerts its cytotoxic activity. The APAN was synthesized and characterized based on their spectral analyses. Scanning for anticancer target of APAN by Swiss software indicated that APAN had highest affinity for protein tyrosine kinase 6 enzyme. Furthermore, Super pred software indicated that APAN can be indicated in hepatic and colorectal cells with 92%. Molecular docking studies indicated that the binding affinity scores of APAN for protein PDB code: 6CZ4 of tyrosine kinase 6 recorded of - 6.6084 and RMSD value of 0.8891°A, while that for protein PDB: 7JL7 of caspase 3 was - 6.1712 and RMSD of 0.8490°A. Treatment of HepG2 and HCT-116 cells with APAN induced cytotoxicity with IC50 of 2.6 and 1.82 µg/mL respectively. In addition, it induced injury and serious morphological changes in cells including, disappearance of microvilli, membrane blebbing, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin. Moreover, APAN significantly increased protein expression of annexin V (apoptotic marker). Furthermore, APAN significantly increased protein expression of caspase 3 and P53. However, it significantly reduced secretion of VEGF protein into the medium and decreased protein expression of PCNA and Ki67 in HepG2 and HCT-116 cells. This study indicated that APAN had cytotoxic activity against HepG2 and HCT-116 cells via increasing the expression of apoptotic proteins and reducing the expression of proliferative proteins.

Serum cystatin C is an early renal dysfunction biomarker in patients with hepatitis C virus.

Background: Hepatitis C virus (HCV) may induce extrahepatic manifestations as acute or chronic renal dysfunction. The aim was to evaluate the diagnostic role of some biomarkers as cystatin C, cryoglobulins, rheumatoid factor (RF), and complement C3 for extrahepatic renal affection in newly diagnosed patients with HCV infection. Methods: Blood and urine were collected from randomized individuals screened for new HCV infection (n=400). The studied populations were divided into 3 groups: control group I: thirty healthy individuals not suffering from either liver or kidney diseases, group IIa: thirty HCV patients who have positive HCV antibody test but showed negative PCR test, and group IIb: thirty HCV patients who showed positive results for both HCV antibody and PCR tests. Results: In HCV group IIb, levels of serum total bilirubin, AST and ALT, and urine albumin/creatinine ratio were increased whereas serum albumin and creatinine clearance were decreased versus other groups. However, the levels of blood urea nitrogen and serum creatinine were still within the normal range in all groups. In HCV group IIb, cystatin C, cryoglobulins, and RF levels were increased; meanwhile, serum creatinine/cystatin C ratio and complement 3 levels were decreased compared to the other groups. HCV-infected patients significantly had higher serum cystatin C (>1.24 mg/L, P<0.001) and lower creatinine/cystatin C ratio (<70.1µMol/mg, P=0.002), and cystatin C was significantly correlated with liver and kidney parameters. Conclusion: High serum cystatin C and low creatinine/cystatin C ratio may be early indicators of mild renal dysfunction with normal serum levels of creatinine in HCV-infected individuals.

Design, Synthesis, and Antiproliferative Activity of Novel Neocryptolepine-Rhodanine Hybrids.

A series of novel neocryptolepine-rhodanine hybrids (9a,b, 11a-d, 14, and 16a,b) have been synthesized by combining neocryptolepine core 5 modified at the C-11 position with rhodanine condensed with the appropriate aryl/hetero aryl aldehydes. Based on these findings, the structures of the hybrids were confirmed by spectral analyses. By employing the MTT assay, all hybrids were tested for their in vitro antiproliferative activity against two cancer cell lines, including MDA-MB-231 (human breast) and HepG-2 (hepatocellular carcinoma). Interestingly, the IC50 values of all hybrids except 9b and 11c showed activity comparable to the standard anticancer drug, 5-fluorouracil, against HepG-2 cancer cells. Furthermore, the cytotoxicity of all the synthesized hybrids was investigated on a normal skin human cell line (BJ-1), and the results showed that these compounds had no significant cytotoxicity toward these healthy cells at the highest concentration used in this study. This study also indicated that the active hybrids exert their cytotoxic activity via the induction of apoptosis. A molecular docking study was used to shed light on the molecular mechanism of their anticancer activity. The docking results revealed that the hybrids exert their mode of action through DNA intercalation. Furthermore, in silico assessment for pharmacokinetic properties was performed on the most potent compounds, which revealed candidates with good bioavailability, high tolerability with cell membranes, and positive drug-likeness values.

Expression of MiRNA-29b and MiRNA-31 and their diagnostic and prognostic values in Egyptian females with breast cancer.

Breast cancer is a major health threat to women globally. Many circulating microRNAs are non-invasive cancer biomarkers. In this study, the expression of miR-29b and miR-31 was assessed in blood samples from 200 patients with breast cancer and wholesome volunteer women using quantitative reverse transcriptase PCR to evaluate their role in the disease. MiR-29b was significantly overexpressed in patients compared to controls. Multivariate regression analysis showed that it was an established risk factor for relapse and mortality. MiR-31 was significantly under-expressed in patients. It was an established risk factor for relapse and was strongly associated with mortality. For the prediction of relapse, miR-29b had a sensitivity of 81.25% and a specificity of 88.24% at a cutoff of > 30.09, while miR-31 had a sensitivity of 87.50% and a specificity of 79.41% at a cutoff of 0.12. The specificity was enhanced to 100% by combining the values of miR-29b and miR-31. In predicting mortality, miR-29b exhibited a sensitivity of 90% and a specificity of 97.5% at a cutoff of > 48.10. At a cutoff of 0.119, miR-31 exhibited a sensitivity of 87.50% and a specificity of 79.41%. High miR-29b expression and low miR-31 expression were linked with a low survival rate. MiR-29b and miR-31 could be useful markers for predicting breast cancer relapse and mortality.

Biochemical and clinical impacts of miR-150 and miR-21 expression levels in diffuse large B cell lymphoma.

Identification of biomarkers is crucial in guiding the treatment decision and improving the future outcomes of DLBCL. The aim of the current study is to detect the biochemical and clinical impacts of miR-150 and miR-21 expression levels in DLBCL. Quantification of serum miR-150 and miR-21 expression levels by real-time PCR after micro-RNA extraction and RT-PCR. At a cutoff point of 2.3 for miR-21, the sensitivity, specificity, positive predictive, and negative predictive values for diagnosis of DLBCL were 98%, 90%, 90.7%, and 97.8%, respectively. At cut-off point (≤19.12) the sensitivity, specificity, the positive predictive and negative predictive values of miR-21 to discriminate stage IV vs stage II DLBCL patients were 68.42%, 80%, 86.7%%,and 57.1%, respectively. Serum miR-150 and serum miR-21 can be used as diagnostic markers for DLBCL patients, but miR-21 is more sensitive than miR-150. Serum miR-21 can be used as prognostic marker for DLBCL patients. It was more sensitive and more specific than miR-150.

Synthesis, Nanoformulations, and In Vitro Anticancer Activity of N-Substituted Side Chain Neocryptolepine Scaffolds.

The naturally occurring neocryptolepine (5-Methylindolo [2,3-b]quinoline) and its analogs exhibited prominent anticancer and antimalarial activity. However, the main problem of this class of compounds is their poor aqueous solubility, hampering their bioavailability and preventing their clinical development. To overcome the problem of insolubility and to improve the physicochemical and the pharmacological properties of 5-Methylindolo [2,3-b]quinoline compounds, this work was designed to encapsulate such efficient medical compounds into mesoporous silica oxide nanoemulsion (SiO2NPs). Thus, in this study, SiO2NPs was loaded with three different concentrations (0.2 g, 0.3, and 0.6 g) of 7b (denoted as NPA). The findings illustrated that the nanoparticles were formed with a spherical shape and exhibited small size (less than 500 nm) using a high concentration of the synthesized chemical compound (NPA, 0.6 g) and good stabilization against agglomeration (more than -30 mv). In addition, NPA-loaded SiO2NPs had no phase separation as observed by our naked eyes even after 30 days. The findings also revealed that the fabricated SiO2NPs could sustain the release of NPA at two different pH levels, 4.5 and 7.4. Additionally, the cell viability of the produced nanoemulsion system loaded with different concentrations of NPA was greater than SiO2NPs without loading, affirming that NPA had a positive impact on increasing the safety and cell viability of the whole nanoemulsion. Based on these obtained promising data, it can be considered that the prepared NPA-loaded SiO2NPs seem to have the potential for use as an effective anticancer drug nanosystem.

The Role of LINC01564, RAMS11, CBX4 and TOP2A in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancers worldwide. Hepatitis C virus (HCV) infection remains a major risk factor for chronic liver disease, cirrhosis, and HCC. To understand the molecular pathogenesis of HCC in chronic HCV infection, many molecular markers are extensively studied, including long noncoding RNAs (lncRNA). Objective: To evaluate the expression levels of lncRNAs (LINC01564, RAMS11), CBX4, and TOP2A in patients with chronic HCV infection and patients with HCC on top of chronic HCV infection and correlate these levels with the clinicopathological features of HCC. Subjects and Methods: One hundred and fifty subjects were enrolled in this study and divided into three groups: group I included 50 patients with HCC on top of chronic hepatitis C (CHC), group II included 50 patients with CHC only, and group III included 50 healthy individuals as a control group. LncRNAs relative expression level was determined by RT-PCR. Results: lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in both patient groups compared to controls (p < 0.001*), with the highest levels in the HCC group compared with the CHC group. Additionally, these levels were significantly positively correlated with the clinicopathological features of HCC. Conclusions: The lncRNA (LINC01564, RAMS11), CBX4, and TOP2A relative expression levels were upregulated in CHC patients­in particular, patients with HCC. Thus, these circulatory lncRNAs may be able to serve as promising noninvasive diagnostic markers for HCC associated with viral C hepatitis.

Phytochemical Characterization and Evaluation of Biological Activities of Egyptian Carob Pods (Ceratonia siliqua L.) Aqueous Extract: In Vitro Study.

Ceratonia siliqua (Carob) is an evergreen Mediterranean tree, and carob pods are potentially nutritive and have medicinal value. The present study was carried out to estimate the possible biological activities of phytochemical-characterized carob pod aqueous extract (CPAE). The phytochemical contents of CPAE were determined by using colorimetric methods and HPLC. In addition, the free radical scavenging properties and anti-diabetic, anti-hemolytic, and antimicrobial activities were estimated by using standardized in vitro protocols. The phytochemical analysis revealed that CPAE was rich in polyphenols, flavonoids, and alkaloids, where it contained a significant amount of gallic acid, catechin, and protocatechuic acid. Furthermore, CPAE exhibited strong antioxidant activity where it prevented the formation of 2, 2-Diphenyl-1-picryl hydrazyl, hydroxyl, and nitric oxide free radicals. Additionally, it had a potent inhibitory effect against digestive enzymes (amylase, maltase, sucrase, and lactase). Moreover, CPAE exhibited anti-Staph aureus, anti-Escherichia coli, anti-Candida albicans, and anti-herpes simplex type I virus (HSV-I). Finally, CPAE protected the erythrocyte membrane from hypotonic solution-induced hemolysis. Altogether, CPAE could be regarded as an interesting source of biologically active antioxidant, anti-diabetic, and antimicrobial preparation for a potential application in pharmaceutical and food supplement fields.

Direct Relationship between Interleukin-10 Gene Polymorphism and Hepatocellular Carcinoma Complicated by Direct Acting Antiviral Treatment of Hepatitis C Virus.

OBJECTIVE: This study aimed to assess the correlation between the genotyping of interleukin-10 (IL-10 polymorphism rs 1800871) and the incidence hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) treated with direct acting antivirals (DAAs). METHOD: For 200 patients with HCV infection who completed DAA treatment and followed up for 1 year, IL-10 polymorphism SNP(-819) rs 1800871 analysis was conducted via real time polymerase chain reaction. During the follow-up period, 100 patients who developed HCC were selected and compared with 100 patients who did not develop any complications. RESULTS: The studied patients were divided into two groups according to the incidence of complications after completion of DAA treatments. During the follow-up, 100 patients with HCV infection who developed HCC were selected and compared with 100 patients with HCV infection who did not develop any complications (positive control group). For the HCC group (n = 100), the mean age was 58.1 ± 6.4 years, with 92.7% being male and 7.3% being female; 91% had cirrhosis, 10% had lymphadenitis, 75% had splenomegaly, and 17% had ascites. In the positive control group (n = 100), mean age was 46.3 ± 9.4 years, with 68% being male and 32% being female; 20% had cirrhosis, 12% had splenomegaly, and 4.2% had ascites. The results demonstrated that sofosbuvir (SOF) + daclatasvir + ribavirin regimen was the most prevalent drug treatment for patients with HCC (72%), while SOF + Simeprevir was the most safe treatment for HCV infection among patients with HCC (2%). CT genotype was the most common genotype in the HCC group (56%), among different drug regimen (67.8%). T allele was the most prevalent in HCC group (61%), while the C allele was the least prevalent (39%). CONCLUSION: IL-10 genotyping may help in selecting the safest and most accurate drug regimen according to the safest genotype response relationship and follow-up of genotype resistance.

Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice.

This study evaluated the ameliorative potential of grape seed extract (GSE) against Ehrlich solid tumor (EST)-induced hepatic tissue alterations in mice. The control group was infused with physiological saline. The second group received GSE (50 mg/kg day by day orally) for 2 weeks. The third group was subcutaneously injected with 2.5 million of EST cells. The fourth group was injected with EST cells and treated with GSE extract simultaneously. The fifth group was injected with EST cells and kept for 2 weeks until the appearance of a solid tumor, then treated with GSE for 2 weeks. The phytochemical analysis of GSE revealed the presence of total phenols (17.442 mg GAE/g) and total flavonoid (6.687 mg CE/g) with antioxidant activity of 81.506 mg TE/g DPPH. The Ehrlich solid tumor significantly raised the activities of ALT, AST, and ALP; the level of alpha fetoprotein (AFP) in serum; and the protein expressions of hepatic proliferating cell nuclear antigen (PCNA) and tumor suppressor protein (P53), as well as induced DNA damage and pathological alterations in liver tissue. However, it significantly reduced serum albumin and total protein levels. In contrast, the co- or post-treatment of EST-bearing mice with GSE reduced the activities of ALT, AST, and ALP; the level AFP in serum; and hepatic P53 and PCNA protein expressions. In addition, it reduced EST-induced hepatic DNA damage and pathological alterations, while it increased serum albumin and total protein levels. This study suggested that GSE is a potent hepatoprotective agent and both co- and post-treatment of EST-bearing mice with GSE almost had the same effects.

Ameliorative effects of 9-diaminoacridine derivative against Ehrlich ascites carcinoma-induced hepatorenal injury in mice.

Ehrlich ascites carcinoma induces hepatorenal injuries while acridine derivatives have antioxidant, anticancer, and anti-inflammatory. Thus, this study evaluated the protective potential of a newly synthesized the 9-diaminoacridine derivative (9-DAAD), N1-(acridin-9-yl) propane-1, 3-diamine hydrochloride, against Ehrlich ascites carcinoma (EAC) induced hepatorenal injury in female mice. Forty female mice were allocated into 4 groups. Group I was injected with 0.1% DMSO subcutaneously and kept a control. Group II received 9-DAAD (30 mg/kg bw/2 days) subcutaneously for 2 weeks. Group III was injected interaperitonealy with 2.5 × 106 cells of EAC/20 g bw. Group IV was injected with EAC as the third group and administered with 9-DAAD as the second group for 2 weeks after induction of EAC. EAC significantly elevated total leukocytes and platelets counts; activities of serum AST, ALT, and ALP; serum levels of alpha-fetoprotein; carcinoembryonic antigen; urea and creatinine; and expression of vascular endothelial growth factor protein in hepatic and renal tissues. Meanwhile it decreased red blood cells count, hemoglobin concentration and hematocrit value. At the same time, it significantly reduced serum levels of total protein and albumin and altered hepatic and renal tissues structures. Also, EAC decreased apoptosis and DNA synthesis in hepatic and renal cells. However, treatment of EAC-bearing mice with 9-DAAD improved liver and kidney structures, functions and modulated EAC altered parameters, as well as it reduced hepatic and renal cells proliferation and DNA synthesis. This study indicated that 9-DAAD had a potential ameliorative effect against EAC-induced hepatorenal injury.

Synthesis, antimicrobial activity, and sustainable release of novel α-aminophosphonate derivatives loaded carrageenan cryogel.

Novel α-aminophosphonates 4 were synthesized via one pot three-component reaction of 4-aminoantipyrine, aldehydes, triphenylphosphite and Lewis acid catalyst. The chemical structures of all the synthesized compounds were elucidated by IR, NMR and MS spectral analysis. The antimicrobial activity of 4 was tested in vitro against pathogenic microbes such as E.coli, S.aureus, A.niger and C.albicans. Three of them (4f-h) exhibited high antimicrobial activity and were loaded to carrageenan cryogel for drug delivery studies. With the aid of cellulose nanofibrils (CNF) as reinforcing material and glyoxal as a cross-linking agent, porous cryogels with improved mechanical properties were obtained. Among all, CAR-7 presents the optimum cryogel sample, which contained around 16% CNF and 0.2 mL/15 mL polymer blend. CAR-7 demonstrated highest mechanical compressive strength, porosity (80%), and swelling capacity (75%). Sustainable release behavior over 24 h was observed for the loaded cryogels. The antimicrobial activity of cryogels against S.aureus showed marginal differences between samples. CAR-9 (loaded with 4f) showed the highest reduction percentage in number of bacterial colonies (99.94%) followed by CAR-11 (loaded with 4h, 99.3%) and finally CAR-10 (loaded with 4g, 99.29%).

Structural Modifications of Nature-Inspired Indoloquinolines: A Mini Review of Their Potential Antiproliferative Activity.

Cryptolepine, neocryptolepine and isocryptolepine are naturally occurring indoloquinoline alkaloids with various spectrum of biological properties. Structural modification is an extremely effective means to improve their bioactivities. This review enumerates several neocryptolepine and isocryptolepine analogues with potent antiproliferative activity against MV4-11 (leukemia), A549 (lung cancer), HCT116 (colon cancer) cell lines in vitro. Its activity towards normal mouse fibroblasts BALB/3T3 was also evaluated. Furthermore, structure activity relationships (SAR) are briefly discussed. The anticancer screening of neocryptolepine derivatives was performed in order to determine their cytotoxic and growth inhibitory activities across the JFCR39 cancer cell line panel.

Grape seeds proanthocyanidin extract ameliorates Ehrlich solid tumor induced renal tissue and DNA damage in mice.

The current study was carried out to evaluate the protective effect of grape seed proanthocyanidins extract (GSPE) against Ehrlich solid tumor (EST) induced renal injury, with the respect to DNA fragmentation and P53 and PCNA proteins expression in renal tissue. A total of 50 female mice were randomly assigned into five groups. Control mice were injected with physiological saline solution. Mice of the 2nd group were administered with GSPE (50 mg/kg bw/every 2day/per OS) for 2 weeks and injected with physiological saline solution. Mice of the 3rd group were injected subcutaneously with 2.5 million cells of EAC/mouse. Mice of the 4th group were injected with EAC as the 3rd group and administered with GSPE as the 2nd group simultaneously for 2 weeks. Mice of the 5th group were injected with EAC as the 3rd group and left for 2 weeks (till development of solid tumor), then treated with GSPE for another 2 weeks. EST significantly increased serum levels of urea, creatinine, potassium and chloride. In addition, it induced renal tissue and DNA injuries and increased P53, PCNA and ki67 proteins expression in renal tissues. On the other hand, it decreased serum levels of sodium and calcium ions. However, treatment of EST bearing mice with GSPE normalized serum levels of the above-mentioned parameters and improved renal tissue structure and reduced renal tissue DNA damage and P53, PCNA and ki67 proteins expression. These results indicated that GSPE is a promising nephron protective agent against EST induced renal injury.

Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon-induced reproductive toxicity in male rats.

This study was designed to evaluate protective effect of Saussurea lappa root aqueous extract against Ethephon (2-chloroethylphosphonic acid)-induced reproductive toxicity in rats. Control group received distilled water. Second group was given S. lappa extract at a dose 50 mg/kg bw. Third group was given Ethephon at a dose 200 mg/kg bw. Fourth, fifth, and sixth groups were given S. lappa extract before, with or after Ethephon administration, respectively. Ethephon intoxication significantly decreased serum levels of follicle stimulating hormone, luteinizing hormone, testosterone, and prolactin. Also, it significantly decreased sperms count, vitality, morphology index, total motility, progressive motility, and proliferating cell nuclear antigen protein expressions in spermatogonia. However, it significantly increased sperms abnormalities, testicular tissue and DNA damages, P53 protein expressions, noprogressive motility, and immotile sperms. In contrast, S. lappa extract ameliorated these alterations. These results indicated that S. lappa had potential preventive and curative effects against Ethephon-induced reproductive toxicity in rats.