The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Curcumin and vitamin C improve immunity of kidney via gene expression against diethyl nitrosamine induced nephrotoxicity in rats:In vivo and molecular docking studies.

Kidney has a crucial role in immunity, so any toxicity occurs for the kidney will result in reduced immunity. The aim of this study is to improve the immune response of insufficient kidneys through immune-related genes. Diethyl Nitrosamine has been used to cause kidney damage in animal models, vitamin C and curcumin have been used to treat impaired kidney. Renal function (urea, uric acid and creatinine) and oxidative stress parameters (superoxide dismutase, malondialdehyde and glutathione peroxidase) will be evaluated in this research work. Molecular docking also will be performed to investigate the role of vitamin C and curcumin in targeting immune response proteins. Also, Complementary component 3, Lipocalin-2, Toll-like receptor 2,Toll-like receptor 4, Kidney injury molecule-1, Interleukin 6, Interleukin-10, Tumor necrosis factor and p38 mitogen-activated protein kinases will be investigated. The obtained results showed that vitamin C and curcumin have good effects in the treatment of impaired kidneys, this was also observed in renal function and oxidative stress parameters, expression levels of proteins and histopathological examinations.

Ameliorative effects of Carica papaya extracts against type II diabetes-induced myocardial pathology and dysfunction in albino rats.

Diabetes is characterized by hyperglycemia. Secondary complications of diabetes are serious risk factors that might lead to cardiovascular diseases. This study evaluated the effects of methanolic extract of Carica papaya fruit and seed in ameliorating the abnormal structural changes in myocardium and functional impairment induced by diabetes in albino rats. The experimental animals were divided into control (C), induced type II diabetes (D), protected seed extract (PSE), protected fruit extract (PFE), treated seed extract (TSE), and treated fruit extract (TFE). The myocardium of diabetic group exhibited disorganized myocardial fibers. Regard both normal, seed and fruit extract groups, which are of almost similar normal pattern of regular oriented muscle fibers. The diabetic group exhibited increased myocardial lipid peroxidation coincides with depletion of superoxide dismutase and increase of the levels of creatine kinase, troponin-1, nuclear factor Kappa B, caspase 3, tumor necrosis factor-α, and activity of lactic dehydrogenase. The diabetic group showed intense dark brown immune reaction against α-smooth muscle actin and P53. Experimental diabetic group protected with either seed and fruit extract exhibited marked amelioration of the assessed parameters. In conclusion, both seed and fruit extract of Carica papaya are of potential medical importance through managing high glucose level and keep myocardium against diabetes-induced cell death.

Immunomodulatory effect of papaya (Carica papaya) pulp and seed extracts as a potential natural treatment for bacterial stress.

The current study evaluated the immunomodulatory effects of Carica papaya pulp and seeds methanol (MeOH) extracts on mice infected with Listeria monocytogenes. Gas chromatography-mass spectrometry analysis identified 10 active constituents in C. papaya seed MeOH extract and 10 compounds in C. papaya pulp MeOH extract. The experimental animals were divided into negative control (G1) group, positive control (G2) group, pulp extract treated (G3) group, and seed extract treated (G4) group. After infection of animals (G2, G3, and G4), treatments were started for 3 weeks. Estimation of the immunological parameters showed a marked decrease in IgM levels and an increase in IgG levels in the treated groups (G3 and G4) compared with those in G2. The proinflammatory cytokines (IL-10, IL-12, IL-1ß, IL-6, and TGF-ß1) were decreased in the treated groups (G3 and G4) compared with those in G2. Nitric oxide levels were also decreased, and the percentages of phagocytosis increased compared with those of G2. The results demonstrated the immunomodulatory and anti-inflammatory effects of C. papaya pulp and seeds MeOH extracts. PRACTICAL APPLICATIONS: Based on the antioxidant and antibacterial activities exhibited by the pulp and seed MeOH extracts investigated in this study, Carica papaya might be considered as a natural source of phytochemicals that could be utilized in novel foods and pharmaceuticals. Further investigation are needed to identify and purify compounds that might be responsible for the observed effects.

Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice.

The current work estimated the antitumour efficacy of melatonin (MLT) on the growth of Ehrlich ascites carcinoma cells inoculated intramuscularly into the hind limbs of female BALB/c mice and to compare its effects with those of adriamycin (ADR). After solid tumours developed, the animals were divided into the three following groups: the tumour-bearing control, MLT-treated (20 mg/kg body weight) and ADR-treated (10 mg/kg body weight) groups. The results showed a significant reduction in the tumour masses of the treated animals in comparison with those of the control group. There were a significant decrease in the malondialdehyde level and a significant elevation of the glutathione concentration and the superoxide dismutase and catalase activities in the MLT and ADR groups. The current study indicated the increased expression levels of P53, caspase-3 and caspase-9 and the decreased expression levels of the rRNA and Bcl2. The MLT and ADR treatments resulted in histological changes, such as a marked degenerative area, the necrosis of neoplastic cells, the appearance of different forms of apoptotic cells and giant cells with condensed chromatin, and a deeply eosinophilic cytoplasm. The MLT and ADR treatments also significantly decreased the Ki-67 protein and vascular endothelial growth factor (VEGF) expression levels in the tumour masses. In conclusion, similar to ADR-treated tumour-bearing mice, MLT suppressed the growth and proliferation of tumour by inducing apoptosis and by inhibiting tumour vascularization. The current data recommend MLT as a safe natural chemotherapeutic adjuvant to overcome cancer progression after a clinical trial validates these results.

Ameliorative impact of Morus alba leaves' aqueous extract against embryonic ophthalmic tissue malformation in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is becoming a serious threat to human health. Morus alba var. multicaulis (Perr.) Loudon (Moraceae) showed a bright future in DM therapy. OBJECTIVE: The study evaluates the antioxidant activity of Morus alba leaves aqueous extract (MLAE) and antidiabetic properties of MLAE in streptozotocin-induced diabetic rats focusing on the ameliorative effects against embryogenesis defects. MATERIALS AND METHODS: MLAE was assayed for bioactive compounds, and antiradical potential. MLAE (100mg/kg body weight) was orally administered to albino rats. DM was induced by intraperitoneal injection of STZ (60mg/kg). The pregnant rats were arranged into 4 groups including control pregnant (C), MLAE-treated group (M), experimental diabetic group (D), and combined diabetic with MLAE-treated group (D-MLAE). The experiment performed in about six months. RESULTS: TPC in MLAE accounted for 11mg GAE/g dry weight (dw) while vitamin C and ß-carotene amounts were 144 and 0.1mg/100g, respectively. MLAE exhibited DPPH, NO and O-2 radical scavenging activities. Treatment of diseased-rats with MLAE resoluted serum glucose levels (378mg/dL), wherein glucose recorded the highest level (830mg/dL) in DM mothers. DM rats recorded the highest level of TC, TG, HDLc, LDLc, and CK, while MLAE treatment reduced those levels. DM rats recorded the highest level of MDA, H2O2, SOD, CAT, GST, GSPase, GSH, GOT, GPT, albumin, bilirubin, arginase, and α-l-fucosidase, while MLAE reduced those levels. Histological photomicrographs of maternal retina showed degenerated ganglionic cells, and neovascularization of nerve fiber layer with edematous inner plexiform layer, and partial loss outer plexiform layer in DM rats. CONCLUSION: MLAE could be used to ameliorate DM. Thus, it might be considered as useful dietary supplements in diabetic patients.