Evolution of Highly Biocompatible and Thermally Stable YVO4:Er3+/Yb3+ Upconversion Mesoporous Hollow Nanospheriods as Drug Carriers for Therapeutic Applications.

In recent times, upconversion nanomaterials with mesoporous hollow structures have gained significant interest as a prospective nano-platform for cancer imaging and therapeutic applications. In this study, we report a highly biocompatible YVO4:1Er3+/10Yb3+ upconversion mesoporous hollow nanospheriods (YVO4:Er3+/Yb3+ UC-MHNSPs) by a facile and rapid self-sacrificing template method. The Rietveld analysis confirmed their pure phase of tetragonal zircon structure. Nitrogen adsorption-desorption isotherms revealed the mesoporous nature of these UC-MHNSPs and the surface area is found to be ~87.46 m2/g. Under near-infrared excitation (980 nm), YVO4:Er3+/Yb3+ UC-MHNSPs showed interesting color tunability from red to green emission. Initially (at 0.4 W), energy back transfer from Er3+ to Yb3+ ions leads to the strong red emission. Whereas at high pump powers (1 W), a fine green emission is observed due to the dominant three-photon excitation process and traditional energy transfer route from Er3+ to Yb3+ ions. The bright red light from the membrane of HeLa cells confirmed the effective cellular uptake of YVO4:Er3+/Yb3+ UC-MHNSPs. The resonant decrease in cell viability on increasing the concentration of curcumin conjugated YVO4:Er3+/Yb3+ UC-MHNSPs established their excellent antitumor activity. Therefore, the acquired results indicate that these YVO4:Er3+/Yb3+ UC-MHNSPs are promising drug carriers for bioimaging and various therapeutic applications.

Nanoparticles mediated tumor microenvironment modulation: current advances and applications.

The tumor microenvironment (TME) plays a key role in cancer development and emergence of drug resistance. TME modulation has recently garnered attention as a potential approach for reprogramming the TME and resensitizing resistant neoplastic niches to existing cancer therapies such as immunotherapy or chemotherapy. Nano-based solutions have important advantages over traditional platform and can be specifically targeted and delivered to desired sites. This review explores novel nano-based approaches aimed at targeting and reprogramming aberrant TME components such as macrophages, fibroblasts, tumor vasculature, hypoxia and ROS pathways. We also discuss how nanoplatforms can be combined with existing anti-tumor regimens such as radiotherapy, immunotherapy, phototherapy or chemotherapy to enhance clinical outcomes in solid tumors.

Highly efficient and robust noble-metal free bifunctional water electrolysis catalyst achieved via complementary charge transfer.

The operating principle of conventional water electrolysis using heterogenous catalysts has been primarily focused on the unidirectional charge transfer within the heterostructure. Herein, multidirectional charge transfer concept has been adopted within heterostructured catalysts to develop an efficient and robust bifunctional water electrolysis catalyst, which comprises perovskite oxides (La0.5Sr0.5CoO3-δ, LSC) and potassium ion-bonded MoSe2 (K-MoSe2). The complementary charge transfer from LSC and K to MoSe2 endows MoSe2 with the electron-rich surface and increased electrical conductivity, which improves the hydrogen evolution reaction (HER) kinetics. Excellent oxygen evolution reaction (OER) kinetics of LSC/K-MoSe2 is also achieved, surpassing that of the noble metal (IrO2), attributed to the enhanced adsorption capability of surface-based oxygen intermediates of the heterostructure. Consequently, the water electrolysis efficiency of LSC/K-MoSe2 exceeds the performance of the state-of-the-art Pt/C||IrO2 couple. Furthermore, LSC/K-MoSe2 exhibits remarkable chronopotentiometric stability over 2,500 h under a high current density of 100 mA cm-2.

Insights into cyclooxygenase-2 inhibition by isolated bioactive compounds 3-caffeoyl-4-dihydrocaffeoyl quinic acid and isorhamnetin 3-O-ß-D-glucopyranoside from Salicornia herbacea.

BACKGROUND: Cyclooxygenase-2 (COX-2) is an important enzyme with numerous biological functions. Overexpression of COX-2 has been associated with various inflammatory-related diseases and therefore, projected as an important pharmacological target. PURPOSE: We aimed to investigate the inhibitory potential of isolated bioactive compounds, 3-caffeoyl-4-dihydrocaffeoyl quinic acid (CDQ) and isorhamnetin 3-O-ß-d-glucopyranoside (IDG), from Salicornia herbacea against COX-2 using both computational and in vitro approaches. METHODS: Computational analysis, including molecular docking, molecular dynamics (MD) simulations, and post-simulations analysis, were employed to estimate the binding affinity and stability of CDQ and IDG in the catalytic pocket of COX-2 against Celecoxib as positive control. These predictions were further evaluated using in vitro enzyme inhibition as well as gene expression mediation in macrophages cells. RESULTS: Molecular docking analysis revealed substantial binding energy of CDQ (-6.1 kcal/mol) and IDG (-5.9 kcal/mol) with COX-2, which are lower than Celecoxib (-8.1 kcal/mol). MD simulations (100 ns) and post simulation analysis exhibited the substantial stability and binding affinity of docked CDQ and IDG compounds with COX-2. In vitro assays indicated significant COX-2 inhibition by CDQ (IC50 = 76.91 ± 2.33 µM) and IDG (IC50 = 126.06 ± 9.44 µM). This result supported the inhibitory potential of isolated bioactive compounds against COX-2. Also, a cellular level study revealed a downregulation of COX-2 expression in tumor necrosis factor-alpha stimulated RAW 264.7 macrophages treated with CDQ and IDG. CONCLUSION: Computational and experimental analysis of CDQ and IDG from S. herbacea established their potential in the inhibition and mediation of COX-2. Hence, CDQ and IDG can be considered for therapeutic development against COX-2 linked disorders, such as inflammation and cancer. Furthermore, CDQ and IDG structures can be served as a lead compound for the development of advanced novel anti-inflammatory drugs.

Metasequoia glyptostroboides potentiates anticancer effect against cervical cancer via intrinsic apoptosis pathway.

This study was undertaken to investigate the anticancer effects of organic extracts derived from the floral cones of Metasequoia glyptostroboides. Dried powder of M. glyptostroboides floral cones was subjected to methanol extraction, and the resulting extract was further partitioned by liquid-liquid extraction using the organic solvents n-hexane, dichloromethane (DME), chloroform, and ethyl acetate in addition to deionized water. HeLa cervical and COS-7 cells were used as a cancer cell model and normal cell control, respectively. The anticancer effect was evaluated by using the Cell Counting Kit-8 assay. The viability of COS-7 cells was found to be 12-fold higher than that of the HeLa cells under the administration of 50 µg/ml of the DME extract. Further, the sub-G1 population was determined by FACS analysis. The number of cells at the sub-G1 phase, which indicates apoptotic cells, was increased approximately fourfold upon treatment with the DME and CE extracts compared with that in the negative control. Furthermore, RT-qPCR and western blotting were used to quantitate the relative RNA and protein levels of the cell death pathway components, respectively. Our results suggest that the extracts of M. glyptostroboides floral cones, especially the DME extract, which possesses several anticancer components, as determined by GC-MS analysis, could a potential natural anticancer agent.

Multifunctional N-P-doped carbon dots for regulation of apoptosis and autophagy in B16F10 melanoma cancer cells and in vitro imaging applications.

Rationale: The present study reports the multifunctional anticancer activity against B16F10 melanoma cancer cells and the bioimaging ability of fluorescent nitrogen-phosphorous-doped carbon dots (NPCDs). Methods: The NPCDs were synthesized using a single-step, thermal treatment and were characterized by TEM, XPS, fluorescence and UV-Vis spectroscopy, and FTIR analysis. The anticancer efficacy of NPCDs was confirmed by using cell viability assay, morphological evaluation, fluorescent live-dead cell assay, mitochondrial potential assay, ROS production, RT-PCR, western-blot analysis, siRNA transfection, and cellular bioimaging ability. Results: The NPCDs inhibited the proliferation of B16F10 melanoma cancer cells after 24 h of treatment and induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated levels of reactive oxygen species. The NPCDs treatment further elevated the levels of pro-apoptotic factors and down-regulated the level of Bcl2 (B-cell lymphoma 2) that weakened the mitochondrial membrane, and activated proteases such as caspases. Treatment with NPCDs also resulted in dose-dependent cell cycle arrest, as indicated by reduced cyclin-dependent kinase (CDK)-2, -4, and -6 protein levels and an enhanced level of p21. More importantly, the NPCDs induced the activation of autophagy by upregulating the protein expression levels of LC3-II and ATG-5 (autophagy-related-5) and by downregulating p62 level, validated by knockdown of ATG-5. Additionally, owing to their excellent luminescence property, these NPCDs were also applicable in cellular bioimaging, as evidenced by the microscopic fluorescence imaging of B16F10 melanoma cells. Conclusion: Based on these findings, we conclude that our newly synthesized NPCDs induced cell cycle arrest, autophagy, and apoptosis in B16F10 melanoma cells and presented good cellular bioimaging capability.

N,P-Doped Carbon Nanodots for Food-Matrix Decontamination, Anticancer Potential, and Cellular Bio-Imaging Applications.

We report a facile one-step thermal treatment method for the synthesis of biocompatible, fluorescent nitrogen-phosphorus-doped carbon nanodots (NPCDs) as multifunctional agents for the food matrix decontamination, cancer targeting, and cellular bio-imaging. NPCDs exhibit high toxicity towards L. monocytogenes, as illustrated by fluorescent live-dead cell counting, disruption of membrane permeability/potential, changes in the levels of cellular ions, genetic materials, and proteins, as well as intracellular production of reactive oxygen species. The tryptophan and protein peaks released in NPCDs treated cells contributed to indole ring breathing and correlated with induced cell death. NPCDs significantly inhibited bacterial biofilm formation on a solid substrate. NPCDs-coated low-density polyethylene (LDPE) film crosslinked with 1% aminopropyltriethoxy silane (APTES) via silane-hydroxyl linking as a food-grade wrap significantly reduced bacterial counts in a raw chicken food model. Furthermore, NPCDs induced apoptosis in HeLa cervical cancer cells, as confirmed by the distorted cell morphology, fluorescence microscopic analysis, presence of fragmented nuclei and the qPCR results of mRNA expression levels of apoptotic markers. Moreover, NPCDs were also applicable in utilized for the cellular bio-imaging of KM12-C colon cancer cells under confocal microscopy owing to their excellent luminescence properties. Overall, NPCDs represent a promising platform to reduce the environmental health risks associated with hazardous pathogens, anticancer targeting, and their application in cellular bio-imaging as multifunctional targets/nanocarriers.

Toxicological evaluation of lotus, ginkgo, and garlic tailored fermented Korean soybean paste (Doenjang) for biogenic amines, aflatoxins, and microbial hazards.

The present study aimed to develop a consortium of nutritive fermented food products, supplemented with phytochemicals, with reduced toxicological contents. We developed new flavored Doenjang products (protein rich) fermented with lotus, ginkgo, and garlic plant extract-based Meju (termed as EMD) as the starter culture and by using traditional Meju (termed as TMD), where these plant extracts were added later during the fermentation process. Fermented Doenjang samples were analyzed for reduced levels of biogenic amines (BAs), aflatoxins, and microbial hazards, (including Bacillus cereus) as well as for their nutritive contents and antioxidant potential, after varying periods of fermentation (0, 3, 6, 9 and 12 months). All Doenjang samples prepared using plant extracts and their mixtures (1% and 10%) showed desired reduction in B. cereus counts, BAs, aflatoxins, and other foodborne pathogens as well as showed potent antioxidant abilities, including phenolic/flavonoid contents. Based on the higher efficiency in reducing various toxicants, Ginkgo biloba leaf extract added TMD samples were selected for the development of Doenjang products as an innovative approach, with great potential to improve the quality and safety of soybean fermented products in the Korean market, offering enhanced health benefits and reduced risks of toxicity.

Garlic augments the functional and nutritional behavior of Doenjang, a traditional Korean fermented soybean paste.

Three different forms of garlic, namely, fresh garlic (2%, 6%, 10%), heat-dried (1%, 2%, 3%) and freeze-dried (1%, 2%, 3%), were supplemented in soybean paste to prepare Doenjang and further evaluated for functional, nutritional and safety aspects. Results showed a considerable antioxidant and anti-proliferative activity of garlic-supplemented Doenjang. As a measure of nutritive value, a high amount of total free amino acids, 4,290.73 mg/100 g-5,492.94 mg/100 g, was observed in prepared Doenjang. Among all preparations, 3% freeze-dried garlic-supplemented Doenjang proved the most effective against gastric adenocarcinoma and lung adenocarcinoma with 50% inhibition concentration of 7.66 ± 0.53 mg/mL and 7.82 ± 0.34 mg/mL, respectively. However 10% fresh-garlicsupplemented Doenjang (GGD-10) showed better activity against colorectal adenocarcinoma (HT29) cell line. Furthermore, GGD-10 effectively reduced colony formation and altered mitochondrial membrane potential of HT29 cells. Absence of pathogenic bacteria (Staphylococcus aureus, Salmonella species and Bacillus cereus) and aflatoxin was observed in Doenjang samples. In addition, nontoxic amount of anti-nutritional biogenic amines was observed in all the samples. The results collectively suggest that the addition of garlic in Doenjang can improve its nutritional and functional value, resulting in the protection of consumers from protein deficiencies and various stress conditions.

Cytotoxic properties of the anthraquinone derivatives isolated from the roots of Rubia philippinensis.

BACKGROUND: Cancer is one of the most frequently occurring diseases and is the second leading cause of death worldwide. In this study, anthraquinone derivatives (Compounds 1-5) were evaluated for their anti-cancer potential against various skin and breast cancer cell lines to assess whether these anthraquinone derivatives may serve as a lead for the augmentation of anti-cancer drug. METHODS: Anthraquinone derivatives, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6'-O-acetyl)-α-rhamnosyl(1 → 2)-ß-glucoside (Comp 1), 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone (Comp 2), and alizarin (Comp 3) were isolated from the dichloromethane fraction of the roots of Rubia philippinensis., whereas ethyl acetate fraction yielded xanthopurpurin (Comp 4) and lucidin-ω-methyl ether (Comp 5). Structures of all the isolated compounds were determined by spectral data analysis. All isolated compounds (Comp 1-5) were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against four different cancer cell lines, i.e. human melanoma (SK-MEL-5), murine melanoma (B16F10), and human breast adenocarcinoma (MCF7 and MDA-MB-231). RESULTS: Significant activity of the compounds 4 and 5 was observed against the breast cancer cell line MDA-MB-231 with IC50 values of 14.65 ± 1.45 and 13.03 ± 0.33 µM, respectively. Encouragingly, IC50 values of 67.89 ± 1.02 and 79.01 ± 0.03 µM against normal kidney epithelial cells (MDCK) were also obtained for compounds 4 and 5, respectively, which indicated very low toxicity and favorable selectivity indices for compounds 4 and 5 in the range of 1.85 to 3.95 and 2.11 to 6.06 against skin cancer cell lines (SK-MEL-5, and B16F10), and breast cancer cell lines (MCF7 and MDA-MB-231), respectively. CONCLUSION: Our results suggested that the compounds 4 (xanthopurpurin) and 5 (lucidin-ω-methyl ether) showed high selective toxicity towards breast cancer cells at lower concentrations without showing toxicity towards normal cells, thus could be of potential as new lead molecules in cancer treatment.

Developments of Cyanobacteria for Nano-Marine Drugs: Relevance of Nanoformulations in Cancer Therapies.

Current trends in the application of nanomaterials are emerging in the nano-biotechnological sector for development of medicines. Cyanobacteria (blue-green algae) are photosynthetic prokaryotes that have applications to human health and numerous biological activities as dietary supplements. Cyanobacteria produce biologically active and chemically diverse compounds such as cyclic peptides, lipopeptides, fatty acid amides, alkaloids, and saccharides. More than 50% of marine cyanobacteria are potentially exploitable for the extraction of bioactive substances, which are effective in killing cancer cells by inducing apoptotic death. The current review emphasizes that not even 10% of microalgal bioactive components have reached commercialized platforms due to difficulties related to solubility. Considering these factors, they should be considered as a potential source of natural products for drug discovery and drug delivery approaches. Nanoformulations employing a wide variety of nanoparticles and their polymerized forms could be an emerging approach to the development of new cancer drugs. This review highlights recent research on microalgae-based medicines or compounds as well as their biomedical applications. This review further discusses the facts, limitations, and commercial market trends related to the use of microalgae for industrial and medicinal purposes.

Antioxidant mechanism of polyphenol-rich Nymphaea nouchali leaf extract protecting DNA damage and attenuating oxidative stress-induced cell death via Nrf2-mediated heme-oxygenase-1 induction coupled with ERK/p38 signaling pathway.

This study investigates the polyphenolic composition and antioxidant mechanism of an ethyl acetate fraction of Nymphaea nouchali leaves (NNLE). Various in vitro assays were performed using RAW 264.7 cells to assess the antioxidant effects of NNLE and to understand the underlying molecular mechanism. High-performance liquid chromatography analysis revealed the presence of gallic acid, catechin, epigallocatechin, epicatechin gallate, caffeic acid, luteolin, and kaempferol as the key polyphenolic composition of NNLE. NNLE had a potent ability to scavenge numerous free radicals through hydrogen atom transfer and/or electron donation. In addition, NNLE prevented the damage of DNA and quenched t-BHP induced generation of ROS without showing toxicity. NNLE was found to combat oxidative stress by enhancing the transcription and translation of both primary antioxidant enzymes and phase-II detoxifying enzymes, especially heme-oxygenase-1 (HO-1). NNLE treatment enhanced Nrf2 accumulation in the nucleus and post-translational phosphorylation level of p38 kinase and extracellular signal-regulated kinase (ERK) in RAW 264.7 cells. Treatment with p38 and ERK inhibitors completely suppressed NNLE-induced Nrf2 and HO-1 expression. We also found that p38 and ERK inhibitors significantly antagonized the increase in cell viability and cellular ROS scavenging activity induced by NNLE. The findings of this study provide scientific evidence on the potential of NNLE as a cost-effective and readily available source of natural phytochemicals, along with the strategy to prevent diseases associated with oxidative stress through attenuating disease progression.

Detection of biogenic amines and microbial safety assessment of novel Meju fermented with addition of Nelumbo nucifera, Ginkgo biloba, and Allium sativum.

Meju, a cooked and fermented soy bean based food product, is used as a major ingredient in Korean traditional fermented foods such as Doenjang. We developed a novel type of Meju using single and combined extracts of Allium sativum (garlic clove), Nelumbo nucifera (lotus leaves), and Ginkgo biloba (ginkgo leaves) at 1% and 10% concentrations to improve the safety of Meju-based fermented products. Biogenic amines (BAs) in protein-rich fermented food products pose considerable toxical risks. The objective of this study was to investigate the effects of adding selected plant extracts in Meju samples during fermentation. Nine BAs, including tryptamine, 2-phenylethylamine, putrescine, cadaverine, agmatine, histamine, tyramine, spermidine and spermine, were isolated from Meju samples after sample derivatization with dansyl chloride and analyzed by high performance liquid chromatography. As a result, all tested Meju samples with added plant extracts showed total BAs levels in the range of 20.12 ±â€¯2.03 to 118.42 ±â€¯10.68 mg/100 g, which were below the safety limit set by various regulatory authorities (USFDA/KFDA/EFSA). However, among all tested Meju samples, LOM10 (Meju fermented with Nelumbo nucifera at 10% concentration) showed higher levels of BAs content than others either due to batch-to-batch variability or reduced beneficial microorganisms and/or due to increase in BA forming microorganisms. Also, none of the samples showed the aflatoxin level above the detection limit. Furthermore, all the tested Meju samples improved microbial safety as confirmed by the complete absence of Salmonella species and Staphylococcus aureus. However, some of the Meju samples showed the presence of coliforms (in range of 1.6 × 100-1.1 × 103 CFU/g), which is under regulatory limits. These results suggested that the use of plant extracts in Meju during fermentation have potential to improve microbial and toxicological safety of Meju products.