Response of male mice to odours of female mice in different stages of oestrous cycle: Self-grooming behaviour and the effect of castration

30-35The behavioural assays were carried out in a Y-maze wherein intact, castrated and testosterone-treated male mice were exposed to oestrus and non-oestrus urine samples. The intact male mice investigated more frequently and spent more time in the Y-maze arm with oestrus urine than in that with non-oestrus urine. In contrast, the castrated mice were not attracted to oestrus urine, whereas testosterone-treated mice showed preference for oestrus urine. The rate of self-grooming was higher in intact males in case of exposure to oestrus urine while the rate was lower with respect to non-oestrus urine. However, castrated mice exhibited less self-grooming behaviour which was partially restored by testosterone treatment. The results suggest that self-grooming behaviour is an indicator of detection and discrimination of oestrus by males, and supports the androgen role in male chemosensory ability to discriminate between oestrus and non-oestrus female odours

Cancer Therapeutic Proficiency of Dual-Targeted Mesoporous Silica Nanocomposite Endorses Combination Drug Delivery

The cargo-loaded mesoporous silica nanoparticles (MSNs) with convenient surface modification can facilitate the development of the innovative nanodrug system. Herein, the present investigation described the electrostatically self-assembled MSNs as a nanosized drug carrier to realize potent synergistic chemotherapy based on the specificity in targeting cytoplasm and nucleus of tumor cells. In this context, the primarily constructed MSNs were subjected with anticancer drug topotecan (TPT) into its large pores. Then, the selective TAT peptide (a nuclear localization signal peptide) was anchored onto TPT-loaded MSNs (TPT-MSN). Subsequently, the positive surface of TPT-MSN-TAT was capped with negatively charged components, poly­(acrylic acid) (PAA)-cRGD peptide and citraconic anhydride (CAH)-metformin (MT), and acted as a smart gatekeeper. Comparatively, PAA-cRGD attached onto MSNs serving as the targeted molecules could upsurge by invasion into cancer cells. Interestingly, the acidic pH of the lysosomal compartment in tumor cells triggers the conjugated CAH from the polymer decorated mesoporous silica (PMS) nanocomposite and could efficiently release MT into the cytoplasm. Consequently, the remaining TPT-MSN-TAT efficiently targets the nucleus and delivers the TPT to improve synergistic chemotherapeutic effects. The precisely released drugs were individually enhanced in the <i>in vitro</i> and <i>in vivo</i> cell killing efficiencies. Thus, the study provides a potential drug delivery podium through combined drugs to realize cancer cell targeting approach

Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer's disease in Wistar rats

Amyloid-β (Aβ) plaque formation, neuronal cell death, and cognitive impairment are the unique symptoms of Alzheimer's disease (AD). No single step remedy is available to treat AD, so the present study aimed to improve the drugability and minimize the abnormal behavioral and biochemical activities in streptozotocin (STZ) induced AD experimental Wistar rats. In particular, we explored the utilization of methacrylated gelatin (GelMA), which is a biopolymeric hydrogel that mimics the natural tissue environment. The synthesized biopolymeric gel contained the drug galantamine (Gal). Investigations were conducted to evaluate the behavioral activities of STZ-induced AD experimental rats under STZ ​+ ​GelMA ​+ ​Gal treatment. The experimental groups comprised the control and STZ, STZ ​+ ​GelMA, STZ ​+ ​Gal, and STZ ​+ ​GelMA ​+ ​Gal (10 ​mg/kg) treated rats. Intracerebroventricular STZ ensures cognitive decline in terms of an increase in the escape latency period, with a decrease in the spontaneous alteration of behavioral activities. Our results indicated decrease Aβ aggregation in the hydrogel-based drug treatment group and significant decreases in the levels of acetylcholinesterase and lipid peroxidation (p ​< ​0.001). In addition, the glutathione and superoxide dismutase activities appeared to be improved in the STZ ​+ ​GelMA ​+ ​Gal group compared with the other treatment groups. Furthermore, histopathological and immunohistochemical experiments showed that the GelMA ​+ ​Gal treated AD rats exhibited significantly improved behavioral and biochemical activities compared with the STZ treated AD rats. Therefore, STZ ​+ ​GelMA ​+ ​Gal administration from the pre-plaque stage may have a potential clinical application in the prevention of AD. Thus, we conclude that hydrogel-based Gal drugs are efficient at decreasing Aβ aggregation and improving the neuroinflammatory process, antioxidant activity, and neuronal growth

Drug-Carrying Capacity and Anticancer Effect of the Folic Acid- and Berberine-Loaded Silver Nanomaterial To Regulate the AKT-ERK Pathway in Breast Cancer

Currently, in clinics, breast cancer is treated with free chemotherapeutic drugs, as a result there is not much therapeutic effect in treated models, leading to substantial systemic toxicity. To overcome these critical problems for the primary outcome, we developed the formulated nanomaterial (FA-PEG@BBR-AgNPs) aimed to specifically target cancer cells via nanoscopic-based drug delivery for getting better therapeutic effectiveness. In the present study, an isoquinoline alkaloid, berberine (BBR), was chosen as a cancer therapeutic agent, encapsulated on citrate-capped silver nanoparticles (AgNPs) through electrostatic interactions (BBR-AgNPs). Then, BBR-AgNPs were conjugated with polyethylene glycol-functionalized folic acid (FA-PEG) via hydrogen bonding interactions (FA-PEG@BBR-AgNPs). The transmission electron microscopy study shows the cellular invasion of the formulated FA-PEG@BBR-AgNPs, indicating the accretion of the nanomaterial at the tumor-specific site. Hence, FA conjugated with the nanomaterial suggests an efficient release of BBR molecules into the specific cancer site. Consequently, the results showed an increase in apoptotic induction via reactive oxygen species and condensed nuclei in cancer cells. Moreover, the western blotting analysis shows reduced/increased expression of PI3K, AKT, Ras, Raf, ERK, VEGF, HIF1α, Bcl-2, Bax, cytochrome <i>c</i>, caspase-9, and caspase-3, thereby enhancing apoptosis. Likewise, the in vivo antitumor efficiency of FA-PEG@BBR-AgNPs showed a significant restraint of tumor progression, and histopathological observations of lung, liver, kidney, heart, and brain tissues proved lesser toxicity of FA-PEG@BBR-AgNPs. Thus, the successfully formulated nanomaterial can serve as a potential drug-discharging vehicle to combat cancer cells by a molecular-based targeting approach

<i>In vivo </i> evaluation of anti-MRSA compound from <i>Streptomyces collinus </i> ICN1 in zebrafish embryos

1155-1161Streptomyces collinus ICN1, an endosymbiotic actinomycete, isolated from the marine sponge Echinodictyum gorgonoides collected from Kanyakumari coast was studied for its antagonistic activity against the clinical pathogen Methicillin-resistant Staphylococcus aureus (MRSA). 16S rRNA gene sequencing confirmed the strain was related to Streptomyces collinus and spore morphology showed smooth surface in scanning electron microscopy. Media optimization for anti MRSA compound production was carried out in solid state fermentation using defined parameters, followed by extraction in methanol. Antagonistic anti-MRSA compound showed 0.91 Rf value in the Thin layer chromatography analysis and 1.53 min retention time in the high performance liquid chromatography analysis at the wavelength of 236 nm. Antagonistic activity of purified compound was studied against MRSA in both in vitro antibacterial assays and in vivo biocompatibility studies in zebrafish embryos. Minimum inhibitory concentration of the compound was found to be 2 µg/ ml by in vitro broth micro dilution method and 4X MIC dose of the compound effective enough to inhibit the pathogenicity of MRSA in in vivo zebrafish infection assay and for the survival of embryos

Fabrication of Minerals Substituted Porous Hydroxyapaptite/Poly(3,4-ethylenedioxy pyrrole-<i>co</i>-3,4-ethylenedioxythiophene) Bilayer Coatings on Surgical Grade Stainless Steel and Its Antibacterial and Biological Activities for Orthopedic Applications

Current strategies of bilayer technology have been aimed mainly at the enhancement of bioactivity, mechanical property and corrosion resistance. In the present investigation, the electropolymerization of poly­(3,4-ethylenedioxypyrrole-<i>co</i>-3,4-ethylenedioxythiophene) (P­(EDOP-<i>co</i>-EDOT)) with various feed ratios of EDOP/EDOT on surgical grade stainless steel (316L SS) and the successive electrodeposition of strontium (Sr²⁺), magnesium (Mg²⁺) and cerium (Ce³⁺) (with 0.05, 0.075 and 0.1 M Ce³⁺) substituted porous hydroxyapatite (M-HA) are successfully combined to produce the bioactive and corrosion resistance P­(EDOP-<i>co</i>-EDOT)/M-HA bilayer coatings for orthopedic applications. The existence of as-developed coatings was confirmed by Fourier transform-infrared spectroscopy (FT-IR), X-ray diffraction (XRD), proton nuclear magnetic resonance spectroscopy (¹H NMR), high resolution scanning electron microscopy (HRSEM), energy dispersive X-ray analysis (EDAX) and atomic force microscopy (AFM). Also, the mechanical and thermal behavior of the bilayer coatings were analyzed. The corrosion resistance of the as-developed coatings and also the influence of copolymer (EDOP:EDOT) feed ratio were studied in Ringer’s solution by electrochemical techniques. The as-obtained results are in accord with those obtained from the chemical analysis using inductively coupled plasma atomic emission spectrometry (ICP-AES). In addition, the antibacterial activity, <i>in vitro</i> bioactivity, cell viability and cell adhesion tests were performed to substantiate the biocompatibility of P­(EDOP-<i>co</i>-EDOT)/M-HA bilayer coatings. On account of these investigations, it is proved that the as-developed bilayer coatings exhibit superior bioactivity and improved corrosion resistance over 316L SS, which is potential for orthopedic applications