Gliclazide in Binary and Ternary Systems Improves Physicochemical Properties, Bioactivity, and Antioxidant Activity.

The poor solubility of the antidiabetic drug gliclazide (Glc) is due to its hydrophobic nature. This research is aimed at improving Glc's solubility and drug release profile, as well as at investigating additional benefits such as bioactivity and antioxidant activity, by forming binary complexes with HPßCD at different w/w ratios (1 : 1, 1 : 2.5, 1 : 4, and 1 : 9) and ternary complexes with HPßCD and Tryp at 1 : 1 : 1, 1 : 1 : 0.27, 1 : 2.5 : 0.27, 1 : 3.6 : 3.6, 1 : 4 : 1, and 1 : 9 : 1, respectively. Complexes were prepared by the physical mixing (PM) and solvent evaporation (SE) methods. The prepared inclusion complexes were meticulously characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra. To verify our findings, the inclusion complexes were evaluated by equilibrium solubility, in vitro drug release profile, kinetic models, and antidiabetic and antioxidant activities in animal models. Our results demonstrated that the solubility and drug release profile were found to be enhanced through binary as well as ternary complexes. Notably, ternary complexes with a ratio of 1 : 9 : 1 showed the highest solubility and drug release profile compared to all other preparations. Data on antioxidant activity indicated that the ternary complex had the higher total antioxidant status (TAS), superoxide dismutase (SOD), and catalase (CAT) activity than the binary complex and Glc alone, in contrast to the diabetic group. In vivo antidiabetic activity data revealed a high percentage reduction in the blood glucose level by ternary complexes (49-52%) compared to the binary complexes (45-46%; p ≤ 0.05). HPßCD and Tryp provide a new platform for overcoming the challenges associated with poorly soluble Glc by providing greater complexing and solubilizing capabilities and imparting ancillary benefits to improve the drug's antidiabetic and antioxidant activities.

Evaluation of Effect of Honey Sugars Analogue Therapy against Breast Cancer Induced by 1-Methyl-1-nitrosourea in In Vivo Breast Cancer Model.

The use of honey as a complementary and alternative medicine is associated with vast range of therapeutic promises. It is established that it exhibits potential innumerable medicinal effects which is attributed to it phenolic, flavonoids, and other diverse compounds profile. However, the effect of honey sugars analogue as its major constituent has not been investigated. This study examined the effect of honey sugars analogue (HSA) namely fructose, glucose, maltose, and sucrose in breast cancer-induced albino Sprague-Dawley (SD) rat models. The treatment was administered when first palpable tumour reached 10-12 mm in size by dividing nulliparous rats (n = 30) into following groups: Group 0 (negative control, n = 10), Group 1 (positive control, n = 10), and Group 2 (received 1.0 g/kg body HSA, n = 10) over a period of 120 days. The effect of treatment against breast cancer was observed with a slower tumour progression, a lower median tumour size, multiplicity, and weight (p < 0.05). The anticancer effect was through amelioration of tumour growth, tumour grading, and haematological parameters. Data also show that HSA administration induces an increased susceptibility of expression of proapoptotic proteins such as Apaf-1, caspase-9, IFN-γ, IFNGR1, and p53, and a reduced expression of antiapoptotic proteins such as E2, ESR1, TNF-α, COX-2, and Bcl-xL 1 in their mechanisms of action. HSA behaves akin to honey. Thus, HSA may modulate breast cancer as an analogue or major profile of honey.

Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial.

Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group (n = 15) and treatment group (n = 15). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed (p > 0.05). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA (p < 0.05), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.

The phytochemical analysis and pharmacological potentials of husk and straw as paddy waste products.

Rice serves as a staple food for one-half of the global population. However, rice production, particularly the rice milling process, results in a substantial amount of paddy waste products (e.g. bran, husk and straw) annually. Because the potentials of bran have been extensively explored in prior studies, the present review focuses exclusively on the phytochemical analysis and pharmacological potentials of husk and straw. This comprehensive review establishes a solid foundation for promoting husk and straw as medicinal substances given their promising pharmacological potentials as bioactive compound sources with therapeutic functions. © 2020 Society of Chemical Industry.

Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation.

Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.

Pattern of collagen fibers and localization of matrix metalloproteinase 2 and 9 during breast cancer invasion.

AIMS AND BACKGROUND: Parenchymal cells naturally interact, react and adapt with the environment including stromal components around them in order to maintain tissue architecture and function. However, studies have shown that this spontaneous interaction will become crucial in assisting cancer invasion. The purpose of the study was to analyze the pattern of collagen deposition and localization of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the tumor microenvironment during breast cancer invasion. METHODS AND STUDY DESIGN: A standard transmission electron microscopy procedure was used together with the immunogold technique with a few modifications. RESULTS: The ultrastructure of fibroblasts in the vicinity of cancer cells was thick, elongated and spindle shaped with nuclear indentations. Desmoplasia was present near the cancer cells. Collagen fibers were still arranged parallel to the cancer cells and fibroblasts but were less dense than collagen fibers far from cancer cells and fibroblasts. Collagen fibers were less dense in the pericellular region because of proteolytic enzyme activity, which facilitates the invasion of breast cancer cells. In immunogold localization analysis, matrix metalloproteinase 9 had consistent localization throughout cancer cells, fibroblast and stroma. In matrix metalloproteinase 2 localization, gold conjugates were more heavily deposited in cancer cells and fibroblasts than in the stroma. CONCLUSIONS: Invasive breast carcinoma is not an independent entity, and its survival depends on the surrounding microenvironment.

Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors.

A total of 96 cases of invasive breast ductal carcinoma were examined for immunohistochemical expression of Bax and Bcl-2 in the epithelial tumor cells and endothelial cells of the blood vessels. We also investigated the association between both proteins in the epithelium in relation to tumor characteristics such as tumor size, grade, lymph node involvement, microvessel density (MVD), hormonal receptors expression and c-erbB-2 overexpression. Bax expression showed a significant association between tumor and endothelial cells (p<0.001) while Bcl-2 expression in tumor cells was inversely associated with that in the endothelial cells (p<0.001). Expression of Bcl-2 in tumor cells was strongly associated with expression of estrogen and progesterone receptors (p=0.003 and p=0.004, respectively). In addition, intratumoral MVD was significantly higher than peritumoral MVD (p<0.001) but not associated with Bax or Bcl-2 expression and other tumor characteristics. We concluded that the number of endothelial cells undergoing apoptosis was in direct linkage with the number of apoptotic tumor cells. Anti-apoptotic activity of the surviving tumor cells appears to propagate cancer progression and this was influenced by the hormonal status of the cells. Tumor angiogenesis was especially promoted in the intratumoral region and angiogenesis was independent of anti-apoptotic activity.

Distinctive features of advancing breast cancer cells and interactions with surrounding stroma observed under the scanning electron microscope.

Breast cancer cells undergo transformation when they spread into surrounding tissues. Studies have shown that cancer cells undergo surface alterations and interact with the surrounding microenvironment during the invasion process. The aim of the present study was to analyse these cancer cell surface alterations and interactions of cancer cells and stroma. Twenty 1-methyl-1-nitrosourea-induced breast cancer samples taken from five rats were fixed in McDowell-Trump fixative and then washed in 0.1 M phosphate buffer. The samples were then treated with osmium tetroxide before being washed in distilled water and subsequently dehydrated through graded ethanols. The dehydrated samples were immersed in hexamethyldisilazane (HMDS), then following removal of excess HMDS, the samples were air dried at room temperature in a dessicator. The dried samples were mounted onto specimen stubs and coated with gold coater before being viewed under a scanning electron microscope. We detected the presence of membrane ruffles on the surface of cancer cells and the formation of unique surface membrane protrusions to enhance movement and adhesion to the surrounding stroma during the process of invasion. Advancing cancer cells demonstrated formation of lamellipodia and invadopodia. The stroma at the advancing edge was desmoplastic with many collagen fibres laid down near the cancer cells. Our data suggest that all of these abnormalities could act as hallmarks of invasiveness for breast cancer.