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This study aims to determine the biochemical compositions and the in vitro antitumour effect of the parotoid gland secretions (PGS) of the Egyptian toad ( Bufo regularis ). The total protein, lipid, carbohydrate contents, total antioxidant capacity (TAC), the median inhibitory concentration (IC 50 ) of 2,2-diphenyl-1-picrylhydrazyl (DPPH), sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) profile, amino acid analysis, gas chromatography-mass spectrometry (GC-MS) analysis and minerals were determined in PGS. The in vitro antitumour effect of PGS against human hepatocellular carcinoma (HepG-2), breast adenocarcinoma (MCF-7) and normal lung fibroblast (WI-38) cell lines were determined. The total protein, lipid and carbohydrate contents of PGS were 250 ± 15 mg/g D.W, 33 ± 3.2 mg/g D.W and 5 ± 0.65 mg/g D.W, respectively, while its TAC was 16.56 ± 0.12 mg/g D.W and the IC 50 of DPPH was 51.95 ± 2.95 mg/mL. Six protein bands varied between 10 and 50 kDa were found in PGS. Among amino acid profile, arginine showed the highest content in PGS. GC-MS analysis showed that 11-octadecenoic acid methyl ester was the highest concentrations in PGS. The half-maximal inhibitory concentrations (IC 50 ) of PGS against HepG-2, MCF-7 and WI-38 cells were 131.82 ± 6.14, 189.71 ± 8.95 and 685.65 ± 33.1 μg/mL, respectively. In vitro study showed that treatment of HepG-2 and MCF-7 cells with PGS increased the percentages of early and late apoptotic. While the percentages of early and late apoptotic WI-38 cells after treatment with PGS were 2.1% and 3.7%. Cell cycle analysis showed that PGS treatment arrested HepG-2 and WI-38 in S-phase, while arrested MCF-7 cells in G2/M phase. The present study concluded that PGS has a potent antioxidant activity with in vitro antitumour effect against HepG-2 and MCF-7 cells., (© Penerbit Universiti Sains Malaysia, 2024.)

Ginger (Gin) has numerous therapeutic properties. One of Gin's most potent components is 6-gingerol, a naturally occurring phenol. This study aimed to investigate the therapeutic impact of gingerol and/or sorafenib on the ATG4/CASP3 and COIIV/COX-2/NF-B Expression as a potential therapy for DAB-induced HCC. Gin was administered to HCC mice induced by p-Dimethylaminoazobenzene (DAB) alone or combined with sorafenib (Sor). Superoxide dismutase (SOD), catalase (CAT), and oxidative stress malondialdehyde (MDA), as well as biochemical markers including AST, ALT, ALP, Albumin, and Bilirubin, were examined. The expression of oncogenes (COIIV, COX-2, NF-κB, and survivin) and tumor suppressor genes (ATG4 and CASP3) was evaluated using qPCR. According to the results, the levels of MDA have been markedly decreased, while SOD and CAT have been increased. Further, the expression levels of tumor suppressor genes were upregulated, whereas the expression levels of oncogene genes were downregulated. Furthermore, in a dose-dependent manner, gingerol has shown the potential to alleviate hepatic portal vein (PV) dilatation and could offer a reliable therapy for HCC. This suggests combining the two compounds may be more effective than alone and that Gin could be a promising therapeutic option for HCC. The binding of Gin and Sor to the active sites of the target genes prevents them from functioning normally, which in turn stops the pathways from carrying out their oncogenic functions. Additionally, COX-2 inhibition reduces the production of certain pro-inflammatory compounds, which further averts oncogenesis. Conclusively, this study indicated that Gin has cytoprotective properties and anti-cancer activity that may be related to controlling oxidative stress. This effect may be achieved by suppressing the COIIV/COX-2/NF-κB pathway and upregulating the ATG4 /CASP3 pathways., (© 2024. The Author(s).)

The term "nanozyme" refers to a nanomaterial possessing enzymatic capabilities, and in recent years, the field of nanozymes has experienced rapid advancement. Nanozymes offer distinct advantages over natural enzymes, including ease of production, cost-effectiveness, prolonged storage capabilities, and exceptional environmental stability. In this review, we provide a concise overview of various common applications of nanozymes, encompassing the detection and removal of pollutants such as pathogens, toxic ions, pesticides, phenols, organic contaminants, air pollution, and antibiotic residues. Furthermore, our focus is directed towards the potential challenges and future developments within the realm of nanozymes. The burgeoning applications of nanozymes in bioscience and technology have kindled significant interest in research in this domain, and it is anticipated that nanozymes will soon become a topic of explosive discussion., (© 2023. The Author(s).)

Cancer cells can become resistant to existing treatments over time, so it is important to develop new treatments that target different pathways to stay ahead of this resistance. Many cancer treatments have severe side effects that can be debilitating and even life-threatening. Developing drugs that can effectively treat cancer while minimizing the risks of these side effects is essential for improving the quality of life of cancer patients. The study was designed to explore whether the combination of dicinnamoyl-L-tartaric (CLT) and sorafenib ((SOR), an anti-cancer drug)) could be used to treat hepatocellular carcinoma (HCC) in the animal model and to assess whether this combination would lead to changes in certain biomarkers associated with the tumour. In this study, 120 male mice were divided into 8 groups of 15 mice each. A number of biochemical parameters were measured, including liver functions, oxidative stress (malondialdehyde, (MDA); nitric oxide (NO)), and antioxidative activity (superoxide dismutase (SOD), and glutathione peroxidase (GPx)). Furthermore, the hepatic expressions of Bax, Beclin1, TNF-α, IL1β, and BCl-2 genes were evaluated by qRT-PCR. The combination of SOR and CLT was found to reduce the levels of liver enzymes, such as AST, ALT, ALP, and GGT, and reduce the pathological changes caused by DAB and PB. The upregulation of TNF-α, IL1β, and Bcl-2 genes suggests that the CLT was able to initiate an inflammatory response to combat the tumor, while the downregulation of the Bax and Beclin1 genes indicates that the CLT was able to reduce the risk of apoptosis in the liver. Furthermore, the combination therapy led to increased expression of cytokines, resulting in an enhanced anti-tumor effect., (© 2023. The Author(s).)

Hepatocellular carcinoma (HCC) is a serious and potentially fatal form of cancer associated with liver damage. New anticancer drugs are increasingly needed due to the increasing number of cancer cases every year. In this study, diarylheptanoids (DAH) from Alpinia officinarum were examined for their antitumor activity against DAB-induced HCC in mice, as well as their ability to reduce liver damage. Assays for cytotoxicity were conducted using MTT. The DAB-induced HCC Swiss albino male mice were given DAH and sorafenib (SOR) either as single treatments or in combination, and the effects on tumour development and progression were monitored. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were evaluated along with biomarkers of liver enzymes (AST, ALT, and GGT). The apoptosis-related gene (CASP8), the apoptosis-related gene (p53), the anti-inflammatory genes (IL-6), the migration-related gene matrix metalloprotease-9 (MMP9), and the angiogenesis-related gene vascular endothelial growth factor (VEGF) were assessed using qRT-PCR in the hepatic tissue. As a final step, DAH and SOR were docked with CASP8 and MMP9 via molecular docking to propose potential mechanisms of action. Our results revealed that the combination of DAH and SOR has a potent inhibitory effect on the growth and viability of the HepG2 cell line. The outcomes demonstrated that DAH and SOR-treated HCC-bearing mice displayed a reduction in the tumour burden and liver damage as demonstrated by (1) parameters of repaired liver function; (2) low levels of hepatic MDA; (3) elevated levels of hepatic T-SOD; (4) p53, IL-6, CASP8, MMP9, and VEGF downregulation; and (5) enhanced hepatic structure. The best results were revealed in mice that were co-treated with DAH (given orally) and SOR (given intraperitoneally). The docking study also proposed that both DAH and SOR could inhibit CASP8 and MMP9's oncogenic activities and had a high affinity for these enzymes. In conclusion, according to study findings, DAH enhances SOR antiproliferative and cytotoxic effects and identifies their molecular targets. Furthermore, the results revealed that DAH was able to boost the anticancer effects of the drug SOR and reduce liver damage caused by HCC in mice. This suggests that DAH could be a potential therapeutic agent against liver cancer., (© 2023. The Author(s).)

Ethnopharmacological Relevance: Artemisia annua L., known as "sweet wormwood," is widely used in Egyptian folk medicine. Egyptians implement the aerial parts in the treatment of respiratory, digestive and sexual dysfunctions. However, the mechanism by which Artemisia annua improves testicular function is still being discovered., Aim of the Study: This study aimed to evaluate the modulatory effects of the crude leaf extract of Artemisia annua (AAE) on a high-fat diet induced testicular dysfunction in rats and compare it with the antilipolytic drug Orlistat., Material and Methods: Forty adult rats were randomly classified and assigned to four groups. The first group typically consumed a balanced diet and served as a negative control (GP1). A high-fat diet-induced obesity was applied to the other three groups for 12 weeks. A positive control remained on HFD for another 8 weeks, which is GP2. Other groups were administered for 8 consecutive weeks either with Orlistat (50 mg/kg body weight) or AAE (100 mg/kg body weight), which have been defined as GP3 and GP4, respectively. Testosterone (TST), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the sera of all groups. In addition, the oxidant/antioxidant biomarkers such as protein carbonyl, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) activities, lactate dehydrogenase (LDH) and creatine kinase isoenzyme-B (CK-MB) were determined. An immunohistochemical stain with the apoptotic marker caspase-3 and the proliferating cell nuclear antigen (PCNA) were also investigated., Results: In the testes of the obese group, the results showed hormonal imbalance, an increase in oxidative stress biomarkers and apoptosis. In the group treated with orlistat (GP3), noticeably more perturbations were noted. The obese rats that had been treated with AAE (GP4) showed a significantly reduced level of oxidative stress, hormonal balance restoration and reduced apoptosis., Conclusions: The crude leaf extract of A. annua is a potential herbal therapeutic for the treatment of obesity-related testicular dysfunction and the restoration of hormonal imbalance in obese rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Eye health of the working population is an essential condition for productivity. Marble industry is processed at large scale at Shaq El Tho'ban area where much dust, crushed pieces of stone, and fluctuating temperatures are endangering employees' health generally and eye health specifically. The objectives of this study were assessing the prevalence of the most common ocular health problems associated with marble industry and investigating the impact of the working environment and occupational risk factors on the oculo-visual status of marble workers. A cross-sectional study was conducted among 250 workers, working at Shaq El Tho'ban area in Egypt during the period from August 2020 to September 2021, using a semi-structured questionnaire and eye examination comprised of full ocular history, visual acuity testing (unaided/aided), slit lamp examination, ophthalmoscopy, and Schirmer's type I and tear break up time tests. The current study showed that gritty sensation (65.2%) and eye dryness (51.2%) were the commonest symptoms complained. By examination, conjunctival hyperemia (59.6%) was the most prevalent finding. By performing dry eye tests, dry eye was diagnosed in 60.4% and 51.2% of workers by Schirmer's test and tear break up time test respectively. The study's results indicated that age, working category, smoking, and diabetes had significant impact on development of ocular symptoms, while working duration, diabetes, smoking, ocular symptoms, and ocular foreign body had significant impact on development of dry eye disease. Implementation of engineering control measures, proper designing, and supply of eye PPE together with adequate health education to all workers about occupational health risks and preventive measures are recommended., (© 2022. The Author(s).)

The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice., (© 2022. The Author(s).)

Heavy metals intoxication causes several health problems that necessitate finding new protective and therapeutic approaches. This study aimed to evaluate the impact of Musa sp. leaves extract (MLE) on hepato-renal toxicities induced by cadmium (Cd) in male mice. The phytochemical screening, metal chelating activity (MCA), and the median lethal dose (LD 50 ) of MLE were determined. Fifty CD-1 male mice were used and intraperitoneally (i.p.) injected with MLE (1000 to 5000 mg/kg b.wt) for MLE LD 50 determination. Another 50 mice were used for evaluating the effect of MLE on Cd toxicity. Blood samples were collected for hematological, liver, and kidney functions assessments. Liver tissue homogenates were used for determination of oxidant/antioxidant parameters. Liver and kidney tissues were harvested for histopathological and molecular investigations. MLE showed potent in vitro antioxidant activities. The MCA and LD 50 of the MLE were 75 µg/mL and 3000 mg/kg b.wt, respectively. MLE showed beneficial therapeutic activity against hepato-renal toxicities in Cd-intoxicated mice, evidenced by improving the hematological, biochemical, histopathological, and molecular alterations.

Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.

The possible renal and hepatic toxicities of ethylenediaminetetraacetic acid (EDTA) in bean cooking media were studied using 100 male albino mice. Two sublethal doses of EDTA were used to explore their toxic effects; 20 mg/kg and 200 mg/kg, which corresponded to 1/100th and 1/10th of LD 50 , respectively. Accordingly, the toxicity study was performed using 50 mice, divided into five groups ( n = 10/group) as follows: group 1 (Gp1) served as a negative control and was orally administered normal saline; group 2 (Gp2) was administered the bean cooking medium; group 3 (Gp3) was administered EDTA (200 mg/kg); group 4 (Gp4) was administered bean cooking medium containing 20 mg/kg of EDTA; and group 5 (Gp5) was administered bean cooking medium containing 200 mg/kg of EDTA. The results showed no significant changes in liver and kidney functions in Gp2 while Gp3, Gp4, and Gp5 exhibited significant increases in adverse liver and kidney function markers. Hematocrit values were significantly decreased in Gp3 and Gp5, while the total white blood cells counts were significantly decreased in Gp3 and significantly increased in Gp5. The number of platelets was decreased in Gp3, Gp4, and Gp5. The blood levels of sodium (Na + ), iron (Fe 2+ ), and calcium (Ca 2+ ) were decreased in Gp3, Gp4, and Gp5 due to the chelating effects of EDTA. The hepatic and renal architectures were disorganized in Gp3, Gp4, and Gp5 with some hemorrhagic manifestations in livers and kidneys of mice. These results demonstrate that EDTA in bean cooking is harmful in mice under the conditions of this study, and the potentially harmful effects in humans supports restricting its use.

One of the activating factors of the cells of the innate immune system is the agonists of toll-like receptors (TLRs). Our earlier publications detailed how poly(I:C), a TLR3 agonist, elevates the NK cell population and the associated antigen-specific CD8 + T cell responses. This study involved a single treatment of the B6 mice with poly(I:C) intraperitoneally. To perform a detailed phenotypic analysis, mononuclear cells were prepared from each of the liver, peripheral blood, and spleen. These cells were then examined for their NK cell population by flow cytometric analysis following cell staining with indicated antibodies. The findings of the study showed that the NK cell population of the liver with an NK1.1 high CD11b high CD11c high B220 + Ly6G - phenotype was elevated following the treatment with poly(I:C). In the absence of CD11b molecule (CR3 -/- mice), poly(I:C) can still increase the remained numbers of NK cells with NK1.1 + CD11b - and NK1.1 + Ly6G - phenotypes in the liver while their numbers in the blood decrease. After the treatment with anti-AGM1 Ab, which induced depletion of NK1.1 + CD11b + cells and partial depletion of CD3 + NK1.1 + and NK1.1 + CD11b - cell populations, poly(I:C) normalized the partial decreases in the numbers of NK cells concomitant with increased numbers of NK1.1 - CD11b + cell population in both liver and blood. Regarding mice with a TLR3 -/- phenotype, their injection with poly(I:C) resulted in the partial elevation in the NK cell population as compared to wild-type B6 mice. To summarise, the TLR3 agonist poly(I:C) results in the elevation of a subset of liver NK cells expressing the two myeloid markers CD11c and CD11b. The effect of poly(I:C) on NK cells is partially dependent on TLR3 and independent of the presence of CD11b., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Mohamed L. Salem et al.)

Background: Cisplatin (CP) has been used in wide range for cancer treatment. Although nephrotoxicity of CP was the main complication, cardiotoxicity has been reported., Objectives: This study investigates the protective role of green tea extract (GTE) and vitamin E (Vit-E) against CP-induced cardiotoxicity, and assesses their impact on CP antitumor efficacy., Materials and Methods: Forty-eight male albino Balb/c mice were randomly divided into six groups, 8 per/group (Gp) were included. Gp1 served as control; Gp2 and Gp3 received oral GTE (400 mg/kg) and Vit-E (100 mg/kg) for 30 consecutive days respectively. Gp4 had received CP (7 mg/kg i.p.) once on the 27th day; Gp5 had received GTE (400 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Gp6 had received Vit-E (100 mg/kg p.o.) for 30 days and CP (7 mg/kg i.p.) on the 27th day. Blood and tissues samples were harvested for biochemical and histopathological investigations. To evaluate the effect of GTE and Vit-E on the antitumor efficacy of CP, 49 female albino mice were inoculated intraperitoneally by Ehrlich ascetic carcinoma -cells (2 × 10 6 /mouse) then treated with none, corn oil, CP, CP/GTE, CP/Vit-E, GTE or Vit-E., Results: CP injection significantly increased Troponin I, CPK, CK-MB, malondialdehyde (MDA), and nitric oxide (NO) levels, while glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase levels were significantly reduced with disruption of cardiac muscle fibers, loss of striations, absence of intercalated disc, and the nuclei are pyknotic. Treatment with GTE and Vit-E improve the biochemical and histological parameters. Treatment with CP alone led to eradication of the tumor cells from the tumor-bearing mice. However, co-administration of GTE or Vit-E orally with CP did not interfere with its therapeutic effects., Conclusion: Treatment with GTE and Vit-E significantly ameliorated the CP cardiotoxicity and improved the myocardial histopathological architecture. GTE and Vit-E may be combined with CP to alleviate cardiotoxicity in cancer chemotherapy without interfering with its antitumor activity., (Copyright © 2019. Published by Elsevier Masson SAS.)

Ethylenediamine terta-acetic acid (EDTA) used to accelerate the cooking process of Vicia (V. faba ) beans. In this study, the effect of cooking with EDTA on the nutritional value of V. faba beans was addressed. Water contents, total proteins, lipids, carbohydrates, minerals and amino acids were determined before and after boiling with EDTA (2 g/L). In both of whole beans and seed coats, the water content was increased after boiling with EDTA. In contrast, the levels of proteins, lipids and carbohydrates were significantly decreased in both the whole beans and seed coats upon boiling with EDTA. Furthermore, the levels of sodium were increased while, the levels of other minerals were decreased. All amino acids were significantly decreased in the whole beans and increased in the seed coats after boiling with EDTA. EDTA addition to V. faba beans during the cooking process decreased the nutritional value of the cooked V. faba beans.

The chemical modification of biodegradable poly(3-hydroxybutyrate) (PHB) is useful for biomedical applications. In this study, the transesterification reaction of PHB was carried out under reflux conditions in the presence of 1,4-butanediol to form telechelic PHB-diol. Further modification of PHB-diol into PHB-diacrylate was carried out by the reaction of PHB-diol with acryloyl chloride. PHB-diacrylate was grafted with amino compounds such as 1,4-butanediamine, 1,3-propanediamine, 1,2-ethylenediamine, piperazine, cyclohexylamine, 2,2'-(ethane-1,2-diylbis(oxy)) diethanamine (jeffamine EDR 148) and morpholine via Michael-type addition reaction. The functionalized amino-PHB polymers were characterized by using FTIR and 1 H NMR techniques. XRD showed that amino-PHB polymers have different crystallinity compared with neat PHB. Some biological activities of amino-PHB polymers were determined such as antibacterial, antioxidant and anticancer activities. In this regard, the results showed that PHB-ethylenediamine revealed a potent antibacterial activity against Staphlococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. All amino-PHB polymers under the study showed reasonable antioxidant activity. Among these polymers, PHB-piperazine showed a potent anticancer effect against in vivo Ehrlich ascetic carcinoma bearing mice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Although the majority of cancers respond to chemotherapy, most cancer types relapse, at least in part, due to the poor immunogenicity of most tumor. We have reported before that treatment of tumor bearing mice with a combination of the anti-cancer chemotherapy cyclophosphamide (CTX) and immunotherapy can result in complete tumor regression using T-cell receptor (TCR) transgenic CD8 + T cells specific to antigens. This study aimed to determine whether chemotherapy can cure immunogenic tumor which expresses non-self-tumor antigen and result in antitumor immunity. Either EL4 cell line, a poorly immunogenic thymoma, or EG7, a clone of EL4 cells transfected with ovalbumin (OVA), as a non-self-antigen were inoculated subcutaneously into wild type or splenectomized C57BL/6 mice and then treated once with intraperitoneal (i.p.) injection of 4 mg CTX/mouse. In certain experiments, the mice were rechallenged with the same tumor type 1-2 months after the primary challenge. Treatment of EL4 bearing mice with CTX induced transient antitumor effect followed by tumor progression. Interestingly, however, treatment of EG7-bearing mice with CTX resulted in regression of early and advanced tumors. EG7 tumor-free mice rejected the second and the third challenges with EG7 cells, but not with challenge EL4 cells. These antitumor effects did not require spleen, since splenectomized mice showed similar antitumor effects of CTX on EG7 cells. Taken together, these data indicate that expression of non-self-antigen by poorly immunogenic tumor might be a reliable means to increase its immunogenicity and its response to chemotherapy.

Fusarium oxysporum, the causal agent of rot and wilt diseases, is one of the most detrimental phytopathogens for the productivity of many economic crops. The present study was conducted to evaluate the potentiality of some xerophytic plants as eco-friendly approach for management of F. oxysporum. Phenolic rich extracts from five plants namely: Horwoodia dicksoniae, Citrullus colocynthis, Gypsophila capillaris, Pulicaria incisa and Rhanterium epapposum were examined in vitro. The different extracts showed high variability in their phenolic and flavonoid contents as well as total antioxidant capacity. A strong positive correlation existed between the antifungal activity of the tested extracts and their contents of both total phenolics and flavonoids (r values are 0.91 and 0.82, respectively). Extract of P. incisa was the most effective in reducing the mycelial growth (IC 50 =0.92mg/ml) and inhibiting the activities of CMCase, pectinase, amylase and protease by 36, 42, 58 and 55%, respectively. The high performance liquid chromatography analysis of P. incisa extract revealed the presence of eight phenolic acids along with five polyphenolic compounds. The flavonol, quercetin and its glycosides rutin and quercetrin were the most abundant followed by the phenolic acids, t-cinnamic, caffeic, ferulic and vanillic. P. incisa extract not only affects the growth and hydrolases of F. oxysporum but also induces ultrastructure changes in the mycelium, as revealed by transmission electron microscopy. To our knowledge, this is the first study to investigate the mechanisms underlying the antifungal activity of P. incisa., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context Cyclophosphamide (CTX) is used to treat different cancer types, although it causes severe hepatotoxicity due to its oxidative stress effect. Rosmarinus officinalis, L. (Lamiaceae) has a therapeutic potential against hepatotoxicity due to its antioxidant activity. Objective The objective of this study is to investigate the phytochemical analysis of the methanol extract of Rosmarinus officianalis leaves (MEROL) and its efficacy against CTX-induced hepatotoxicity. Materials and methods The phytochemical analyses were assessed spectrophotometericaly. To assess the MEROL efficacy, 72 Swiss albino mice were divided into six groups. Group 1 was control, groups 2 and 3 included mice which were injected intraperitoneally (i.p.) with 100 or 200 mg/kg of MEROL at days 1, 4, 7, 10, 13 and 16; group 4 was injected (i.p.) with CTX (200 mg/kg) at day 17, groups 5 and 6 were injected (i.p.) with MEROL as groups 3 and 4 followed by 200 mg/kg CTX at day 17, respectively. At day 22, six mice from each group were sacrificed and the others were sacrificed at day 37. Results MEROL has a high content of total phenolics, saponins, total antioxidant capacity and DPPH radical scavenging activity. The median lethal dose (LD50) value of MEROL was 4.125 g/kg b.w. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 55 μg/mL. Pretreatment with 100 mg/kg MEROL for 16 d ameliorated CTX-induced hepatotoxicity represented in lowering the levels of the aspartate aminotransferase (AST) and lipid profile and minimizing the histological damage. Conclusions Pretreatment with 100 mg/kg b.w. MEROL mitigated CTX-induced hepatotoxicity due to its antioxidant activity.

In this paper, we theoretically investigate the effect of an external magnetic field on the properties of photonic band structures in two-dimensional n-doped semiconductor photonic crystals. We used the frequency-dependent plane wave expansion method. The numerical results reveal that the external magnetic field has a significant effect on the permittivity of the semiconductor materials. Therefore, the photonic band structures can be strongly tuned and controlled. The proposed structure is a good candidate for many applications, including filters, switches, and modulators in optoelectronics and microwave devices.

Context: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent., Objective: This study elucidates the protective effects of propolis against CTX-induced changes in mice., Materials and Methods: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS), group 2 was injected with 100 mg/kg/d propolis, group 3 was injected with a single dose of CTX (200 mg/kg), and group 4 was injected with a single dose of CTX (200 mg/kg) followed by propolis (100 mg/kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters., Results: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved., Conclusions: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.

Much of previous work has been devoted in studying complete band gaps for bulk phononic crystal (PC). In this paper, we theoretically investigate the existence and widths of these gaps for PC plates. We focus our attention on steel rods of square cross sectional area embedded in epoxy matrix. The equations for calculating the dispersion relation for square rods in a square or a triangular lattice have been derived. Our analysis is based on super cell plane wave expansion (SC-PWE) method. The influence of inclusions filling factor and plate thickness on the existence and width of the phononic band gaps has been discussed. Our calculations show that there is a certain filling factor (f=0.55) below which arrangement of square rods in a triangular lattice is superior to the arrangement in a square lattice. A comparison between square and circular cross sectional rods reveals that the former has superior normalized gap width than the latter in case of a square lattice. This situation is switched in case of a triangular lattice. Moreover, a maximum normalized gap width of 0.7 can be achieved for PC plate of square rods embedded in a square lattice and having height 90% of the lattice constant., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Preconditioning a recipient host with lymphodepletion can markedly augment adoptive T cell therapy. However, the precise mechanisms involved are poorly understood. In a recent study, we observed a significant increase in the circulating levels of dendritic cells (DCs; CD11c(+)CD11b(+)) during the recovery from cyclophosphamide (CTX)-induced lymphodepletion. Herein, we demonstrate that the CTX-induced DC expansion was not altered by adjuvant chemotherapy or tumor burden but was augmented by coadministration of granulocyte-colony stimulating factor. Although the increase in the number of DCs was preceded by a systemic expansion of a population expressing the phenotype of myeloid-derived suppressor cells (Gr-1(+)CD11b(+)), depletion of these Gr-1(+) cells had no effect on the noted expansion. Moreover, when Gr-1(high)CD11b(high) cells were sorted from CTX-treated mice and adoptively transferred into control or CTX-treated recipients, they did not differentiate into DCs. Post-CTX expansion of DCs was associated with proliferation of DCs in bone marrow (BM) during the lymphopenic phase and in the blood and spleen during the recovery phase. Furthermore, adoptive transfer of BM cells from CTX-treated mice produced equal numbers of DCs in the blood of either CTX-treated or untreated recipients. CTX induced a dynamic surge in the expression of growth factors and chemokines in BM, where CCR2 and Flt3 signaling pathways were critical for DC expansion. In sum, our data suggest that CTX induces proliferation of DCs in BM prior to their expansion in the periphery. Targeting DCs at these phases would significantly improve their contribution to the clinical application of lymphodepletion to adoptive immunotherapy.

We have shown recently that cyclophosphamide (CTX) treatment induced a marked increase in the numbers of immature dendritic cells (DCs) in blood, coinciding with enhanced antigen-specific responses of the adoptively transferred CD8(+) T cells. Because this DC expansion was preceded by DC proliferation in bone marrow (BM), we tested whether BM post CTX treatment can generate higher numbers of functional DCs. BM was harvested three days after treatment of C57BL/6 mice with PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from CTX-treated mice showed faster generation and yielded higher numbers of DCs with superior activation in response to toll-like receptor (TLR) agonists. Vaccination with peptide-pulsed DCs generated from BM from CTX-treated mice induced comparable adjuvant effects to those induced by control DCs. Taken together, post CTX BM harbors higher numbers of DC precursors capable of differentiating into functional DCs, which be targeted to create host microenvironment riches in activated DCs upon treatment with TLR agonists., (Published by Elsevier Inc.)

Recent preclinical studies suggest that vaccination following adoptive transfer of CD8(+) T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8(+) T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8-16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp100(25-33) melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8(+) T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.

We have recently reported that the toll-like receptor 3 (TLR3) agonist poly(I:C) induces adjuvant effects to post vaccination CD8+ T cells responses through rapid induction of innate mediators, including NK cells, macrophages, dendritic cells (DCs), and inflammatory cytokines. However, whether this TLR3 agonist directly targets CD8+ T cells needs to be carefully investigated. In this study, we found that optimal post vaccination CD8+ T cell responses to ex vivo DC-based vaccination requires triggering of TLR3 signaling pathway in DCs in vitro as well as in the recipient host, indicating a role for other cell types. Real-time PCR analysis revealed that TLRs (TLR1-TLR13) are expressed in purified (>99% pure) CD4+ and CD8+ T cells from C57BL/6 and BALB/c mice, where the magnitude of the expression was strain and cell type dependent. In vitro, treatment of these purified T cells with poly(I:C) modulated the expression of TLRs including TLR3. Furthermore, non-specific and antigen-specific stimulation of CD8+ T cells by phorbol myristate acetate and MHC class I peptide-pulsed splenocytes, respectively, modulated TLR expression in purified CD4+ and CD8+ T cells. Importantly, brief conditioning of purified naïve TCR transgenic OT-1 (CD8+) T cells in vitro with poly(I:C) induced activation of these cells in absence of antigen stimulation. Interestingly, when these in vitro poly(I:C)-conditioned OT-1 cells were adoptively transferred into naïve recipient followed by peptide vaccination, they showed superior expansion and activation to their naïve counterparts. These results suggest that CD8+ T cells can be activated by triggering their TLR3. Furthermore, the data support the notion of direct involvement of TLRs in adaptive immune responses.

Although cyclophosphamide (CTX) has been clearly shown to enhance active specific and adoptive immunotherapies, the mechanism(s) underlying these beneficial effects have not been clearly defined. To define the impact of CTX preconditioning on the antigen-specific CD8 T-cell response to peptide vaccination, we used an adoptive transfer model based on the OT-1 T-cell receptor transgenic mouse. CTX preconditioning dramatically enhanced the antigen-specific CD8 T-cell response to peptide vaccination. Specifically, CTX significantly enhanced the expansion and function of responding CD8 T cells as demonstrated by flow cytometry and cytokine production. In parallel experiments, we attempted to define the mechanism(s) underlying these beneficial effects of CTX therapy. CTX therapy increased the relative number and activation status of myeloid dendritic cells, and was associated with the induction of significant levels of the inflammatory cytokines interferon-alpha, monocyte chemoattractant protein-1, and IL-6. Adoptive transfer experiments into type I IFNR-/- and CR3-/- mice confirmed that the beneficial effects of CTX were at least partially dependent on type I interferons and myeloid cells. Adoptive transfer of up to 150x10(6) naive spleen cells at the time of antigen-specific CD8 T-cell transfer did not abrogate the effects of CTX therapy, suggesting that the creation of a niche in the immune system may not be required. CTX decreased the absolute, but not relative number of CD4+CD25+ Treg cells, consistent with the possibility that regulatory T cells may be targeted by CTX therapy. Of note, combination therapy with CTX and a synthetic TLR3 agonist further enhanced the antigen-specific CD8+ T-cell response. Taken together, our data suggest that CTX modulates specific components of the innate immune system resulting in a beneficial host microenvironment. Specific targeting of these components may enhance the effectiveness of CTX preconditioning for adoptive immunotherapy.

Poly (I:C), a TLR3 ligand, has shown promise as a vaccine adjuvant to CD8(+) T cell responses. The underlying mechanisms involved in creating this adjuvant response in vivo, however, have not been well defined. In this study, we explored the contribution of NK cells and inflammatory cytokines in mediation the poly (I:C) adjuvant effects. Enhanced antigen-specific CD8(+) T cell responses were observed only when poly (I:C) was administered within 4h of peptide vaccination. Poly (I:C) treatment was associated with a rapid induction of inflammatory cytokines in the serum, including IL-6, IL-10, MCP-1, TNF-alpha, IFN-alpha, and IFN-gamma, and selective increases in the numbers of NK (NK1.1(+)CD11b(+)) cells and Mvarphi (NK1.1(-)CD11b(+)), but not NK T (CD3(+)NK1.1(+)) cells. NK cells were required for the adjuvant effects of poly (I:C). Poly (I:C) treatment in TNF-alpha, type I IFNR, IFN-gamma, IL-6, IL-12Rbeta2, or IL-15 gene-deficient mice revealed a reciprocal interaction and interdependence in the induction of these cytokines, where the absence of one cytokine impacted on the production of others. Further, the adjuvant effects of poly (I:C) were dependent on the endogenous levels of type I IFNs, TNF-alpha, IFN-gamma, IL-12, and IL-15. IFN-alpha and IFN-beta, but not TNF-alpha or IL-6, were able to mimic the adjuvant effects of poly (I:C). We conclude that the adjuvant effects of poly (I:C) on antigen-specific CD8(+) T cells appeared to be exquisitely dependent on the rapid induction of certain beneficial cytokines produced in part by NK cells.

Several techniques have been described and utilized for recession and resection of the extraocular muscles with various technical difficulties and complications. Two new instruments have been designed which may minimize surgical difficulties and provide more accurate and consistent measurements in muscle surgery.