The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body’s circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the gradual development of multiple cysts through both kidneys. The normal kidney tubules cavities filled with fluid portions and lead to progressive renal impairment, frequently with the additional problems of hypertension, infection, and pain which leads to kidney failure. The mutation of PKD1 gene and its product polycystin-1, a membrane-bound multi domain protein mainly cause ADPKD. Hence, our study attempted to investigate the impact of structural and atom level changes in polycystin-1 PKD domain due to critical mutation R324L in the dynamic system. Using the powerful computational techniques like mutation modeling, molecular dynamics (MD) simulations and principal component analysis (PCA) are followed for the comparison of wild type protein and mutant R324L. The trajectory analysis from 50 ns simulation results showed the major conformational changes in atomic level of mutant protein that significantly affects the function of polycystin-1. Moreover, principal component analysis elucidated the abrupt change in overall motion of the protein due to mutation. Thus, our study deciphered the mutation R324L drastically affects the polycystin-1 in structural level and plays critical in ADPKD mechanism.

Glycoprotein (GLP) with a molecular mass of ~48 kDa was isolated from Codium decorticatum. Further, characterization of GLP and its potent anti-cancer activities was discussed. GLP is a glycoprotein with 36.24% carbohydrate, composed of rhamnose, galactose, glucose and mannose with a mole ratio of 38:30:26:6. Rhamnose and galactose are thus the main monosaccharides in GLP. FT-IR and NMR spectra proved that GLP contained protein and carbohydrate portions with (1→4)-linked β-galactose residues and β-linked glucose residues. Secondary structure of GLP was estimated using circular dichroism (CD) analysis. Furthermore mass spectrometric analysis was performed for identification of protein using mascot search. The findings of this study serve as a reference for better understanding of the bioactivity of glycoprotein in green algae. Analysis of anticancer potential of this GLP revealed a remarkable inhibition of cell growth in breast, cervical and lung cancer cells.

Removal of heavy metals from industrial wastes has been an important environmental research area. In the present study a mixture of two different types of biosorbent for removal of copper from water was investigated. Three types of biosorbents were tested i.e. EG, UA and a combination of both (EG+UA). The batch scale studies were carried out to study the effect of pH, metal concentration and contact time on adsorption capacity. Maximum removal percentage of Cu (II) by EG was about 99% at pH 5 UA and EG+UA got the maximum removal of Cu of about 68%, 74% at pH 8 respectively. In the metal concentration studies EG and UA adsorbed the increased concentration of Cu (II), the combination of adsorbents showed 79.8% adsorption for Cu at 100mg/L and for other concentrations of 200mg/L, 300mg/L, 400mg/L and 500mg/L it showed 68.6%, 67.6%, 58.8 and 57.1% respectively. The maximum Cu (II) removal exhibited by the EG+UA combination was 79.85% obtained for the optimal contact time of 120 min. EG showed Cu (II) removal was maximum up to 99% and UA showed the removal was maximum up to 84% with the contact time 120 min. The morphology characterization of the three adsorbent systems was investigated using the Scanning Electron Microscope (SEM). The Langmuir isotherm was found to be the best-fitting isotherm which indicates the experimental values match with the theoretical reported values. In the kinetic studies the higher R2 values confirm that the adsorption data are well explained by pseudo second order kinetics.

Human ?-aminobutyric acid aminotransferase (GABA-AT), a pyridoxal phosphate dependent enzyme is responsible for the degradation of the inhibitory neurotransmitter GABA. Currently, GABA-AT is a potential drug target for epilepsy due to the selective inhibition in brain. In this computational study, we mainly focus on screening of novel lead candidates against GABA-AT using hexonic derivatives. Structure based virtual screening is performed in Vina that screened top hits based on least binding affinity. Further re-docking on hits is performed in AutoDock results in identification of leads with favorable binding energy and hydrogen bond interactions confirmed the effective inhibition. In conclusion, leads 3-aminohex-5-enoic acid and AG-E-60842 can acts as specific leads for GABA-AT and assist in discovery of novel anti-epileptic drugs.

Marine algae are known to produce an extensive variety of bioactive metabolites and several novel drugs have been derived for the pharmaceutical industries.However glycoproteins from the algae have not been adequately explored for their potential as a source of bioactive substances.The objectives of this study were to investigate the antioxidant activity effect of glycoprotein (GLP).In the experiment of the radical elimination ability by means of 1,1-diphenyl-2-picryhydrazyl (DPPH) expressed anti-oxidative effect depending on the concentration considering GLP.Hydroxyl (OH) radical, superoxide radical (O2) and nitric oxide radial (NO) scavenging also showed that antioxidant abilities in the dose depended concentration.These results express that GLP eliminates reactive oxygen species (ROS), protect cell membrane, and can act as antioxidants.Therefore, it is thought that GLP can be used to new material of food supplements related to antioxidants.

Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC₅₀ values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 μg/mL (IC₂₅), 55 ± 0.32 μg/mL (IC₅₀), and 30 ± 0.43 μg/mL (IC₇₅) and 90 ± 0.57 μg/mL (IC₂₅), 80 ± 0.48 μg/mL (IC₅₀), and 60 ± 0.26 μg/mL (IC₇₅), respectively. Chromatin condensation and poly(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨ(m)), bax/bcl-2 dysregulation, cytochrome c release, and activation of caspases 3 and 9. Apoptosis-associated factors such as reactive oxygen species (ROS) formation and loss of ΔΨ(m) were evaluated by DCFH-DA staining and flow cytometry, respectively. Cell cycle arrest of G₂/M phase and expression of apoptosis associated proteins were determined using flow cytometry and Western blotting, respectively.

Crude fucoidan from Sargassum plagiophyllum extracted from blade and purified by Q-Sepharose fast flow anion-exchange chromatography and three fucoidan fractions were obtained. Maximum sulphate containing fucoidan fraction was considered as purified fucoidan and purity was checked with agarose gel electrophoresis. The monosaccharides of purified fucoidan analysed by HPLC revealed the presence of the sugars such as fucose as a major sugar were 70.8 mol%. The percentages of other sugars were galactose (13.5%), xylose (2.5%) and mannose (11.2%). GPC was used to analyse molecular weight of purified fucoidan and it was found to be 35 kDa. The levels of ICDH, SDH, MDH, a-KGDH, Phase-I biotransformation enzymes, and Phase-II biotransformation enzymes were decreased in cancer bearing animals which may be due to oxidative stress and mitochondrial damage and fucoidan restored these enzyme activities. The inhibition of carcinogen metabolic activation indicates the anticancer activity of fucoidan in DEN induced liver cancer.