Vitamin C Supplementation, APOE4 Genotype and Cognitive Functioning in a Rural-Dwelling Cohort.

OBJECTIVE: Apolipoprotein E4 (APOE4) genotype has been implicated as a moderating factor in cognitive function studies. Although prior studies have suggested that vitamin C is associated with better cognitive function in elders, link between the two has been mixed. Limited data exist as to whether the APOE4 genotype influences these associations. Therefore, this study sought to determine whether the association between vitamin C and cognition in a rural community dwelling cohort differs by the APOE4 genotype. DESIGN AND PARTICIPANTS: Data were analyzed on 582 participants (n=183 men; n=399 women) from a rural community-based cohort. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status and The Executive Interview. APOE genotyping was ascertained by standard methods. The relation between vitamin C supplementation and cognition were analyzed first with ANOVA and then ANCOVA with age, gender, education as covariates. Analyses were initially run in the full sample and then split by APOE4 presence (yes/no). RESULTS: Overall, Vitamin C supplementation was associated with significantly better immediate memory (p=0.04), visuospatial skills (p=0.002), language (p=0.01), and global cognitive functioning (p=0.006). Among APOE4 non-carriers, vitamin C supplementation was positively associated with immediate memory (F[1,392] =6.7, p=0.01), visuospatial skills (F[1,391]=10.6, p=0.001), language (F[1,392]=13.0, p<0.001), attention (F[1,386]=7.9, p=0.005, and global cognition (F[1,382]=11.0, p=0.001. However, there was no significant link between vitamin C supplementation and cognition among APOE4 carriers. CONCLUSION: Vitamin C supplementation was found to be positively associated with cognition among this rural-dwelling community-based sample; however, the associations appeared to differ by APOE4 status. These data may suggest that targeted genotype-specific cognitive enhancement studies are needed to clarify the potential benefits of vitamin C supplementation.

Oxidative stress plays an important role in zoledronic acid-induced autophagy.

Several pre-clinical and clinical studies have demonstrated zoledronic acid (Zol), which regulates the mevalonate pathway, has efficient anti-cancer effects. Zol can also induce autophagy. The aim of this study is to add new understanding to the mechanism of autophagy induction by Zol. LC3B-II, the marker for autophagy was increased by Zol treatment in breast cancer cells. Autophagosomes induced by Zol were visualized and quantified in both transient (pDendra2-hLC3) and stable MCF-7-GFP-LC3 cell lines. Acidic vesicular organelles were quantified using acridine orange. Zol induced a dose and time dependent autophagy. Treatment of Zol increased oxidative stress in MCF-7 cells, which was reversed by GGOH or anti-oxidants. On the other hand, treatment with GGOH or anti-oxidants resulted in decreased levels of LC3B-II. Further, the induced autophagy was irreversible, as the washout of Zol after 2 h or 24 h resulted in similar levels of autophagy, as induced by continuous treatment after 72 h. Thus, it can be summarized that Zol can induce a dose dependent but irreversible autophagy, by its effect on the mevalonate pathway and oxidative stress. This study adds to the understanding of the mechanism of action of Zol, and that it can induce autophagy at clinically relevant shorter exposure times in cancer cells.

Role of NF-κB as a Prognostic Marker in Breast Cancer : A Pilot Study in Indian Patients.

The nuclear factor κB (NF-κB) is a superfamily of transcription factors. It plays an important role in development & progression of cancer. This study was conducted in a tertiary care centre to investigate the significance of NF-κB as a prognostic marker in breast cancer and study its relation with established prognostic markers such as tumor grade, lymph node status, hormone receptor & HER-2/neu expression. We measured NF-κB expression of breast cancer tissue as a test sample & from fibroadenoma as a control. Measurement was done by Western Blot Technique using p65 protein of NF-κB super family of transcription factors. ER,PR and HER-2/neu were measured by immunohistochemistry methods. NF-κB/p65 is significantly associated with large tumor size (≥5 cm), high grade tumors, negative ER, negative PR, positive HER-2/neu and high NPI (≥5.4) scores. NF-κB/p65 expression implies aggressive biological behaviour of breast cancer & this study validates significant association of NF-κB /p65 overexpression with large tumor size, negative estrogen & progesterone receptor status and overexpression of c-erbB2 oncoprotein.

Transparent, luminescent, antibacterial and patternable film forming composites of graphene oxide/reduced graphene oxide.

Multifunctional graphene oxide/reduced graphene oxide (GO/RGO) composites were prepared through electrostatic interaction using biocompatible ingredients. Different functionalities were added to GO/RGO by anchoring materials such as native lactoferrin (NLf), NLf protected Au clusters (designated as Au@NLf), chitosan (Ch) and combinations thereof. Anchoring of Ch and NLf enhances the antibacterial property of RGO/GO. The addition of Ch to RGO/GO not only helped in forming stable dispersions but also helped in fabricating large (cm(2)) area films through a simple solvent evaporation technique. Functionalities such as photoluminescence were added to Ch-RGO/GO composites by anchoring Au@NLf on it. The composites thus formed showed stable luminescence in presence of various metal ions in the solid state. The composite showed reasonable stability against pH and temperature variations as well. The as-prepared films were transparent and the transparency could be modulated by controlling the concentration of RGO/GO in the composite. The antibacterial property and ability to form stable thin films may provide an opportunity to use such composites for medical and environmental remediation applications as well. Erasable patterns were fabricated on the film by stamping required patterns under compressive pressure. Luminescent patterns can be inscribed on the film and can be erased by simply wetting it. Such films with erasable information may be useful for security applications.

Diuretic and natriuretic activity of two mistletoe species in rats.

In different cultural groups, the hemiparasitic plants of the families Loranthaceae and Viscaceae (mistletoes) are frequently used in the treatment of hypertension and/or as diuretic agents. However, it remains unclear as to what commonality makes them diuretic agents or a remedy for hypertension. In this article, the diuretic activity of methanol extracts of Viscum articulatum (VA) Burm. f. and Helicanthus elastica (HE) (Ders.) Dans. in rats is reported. The extracts were administered orally at doses of 100, 200 and 400 mg/kg to rats that had been fasted and deprived of water for 18 hours. Investigations were carried out for diuretic, saluretic and natriuretic effects. The polyphenolic and triterpenoid contents were determined quantitatively using chemical assays and high performance liquid chromatography (HPLC) analysis, respectively. The extracts of VA and HE demonstrated significant and dose-dependent diuretic activity in rats. It was found that while VA mimics the furosemide pattern, HE demonstrated a dose-dependent increase in diuresis, along with an increase in potassium-sparing effects. Phytochemical analysis revealed that polyphenolics and triterpenoids, such as oleanolic acid and lupeol, are the major phytochemicals involved. It was also found that in different combinations, these phytochemicals differed in the way they influenced the electrolyte excretion. A higher content of polyphenolics in association with lower triterpenoid content was found to favor potassium-sparing effects.

Microwave technique in histopathology and its comparison with the conventional technique.

125 formalin fixed human tissues from different organs and 50 fresh animal tissues were taken. Each tissue piece was divided into two. Fresh animal tissues were fixed and processed in a domestic microwave oven and formalin fixed tissue were only processed in microwave oven. Simultaneous conventional processing was also carried out. Among the fresh tissues, 34 pieces were fixed in 10% formalin and 16 were stabilized in normal saline, with microwave irradiation. For histoprocessing graded ethanol (70% and absolute) for 150 tissues and graded isopropanol (70% and absolute) for 25 tissues were used for dehydration in microwave technique. Chloroform for 95 tissues, xylene for 15 tissues and isopropanol for 65 tissues were used as clearing agent in microwave technique. Liquid paraffin was impregnating agent in all 175 cases. The oven was operated at 50% power for 10 cases and 40% power for 165 cases. Recording of temperature could not be done. Regarding fixation with formalin 80% cases gave satisfactory result, while with normal saline, only 30% cases were satisfactory. Regarding dehydration with ethanol 80% were satisfactory and with isopropanol 60% were satisfactory. Regarding clearing--both chloroform and isopropyl alcohol gave satisfactory results in 80% cases but with, xylene tissues were fragmented and brittle.