The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,Llactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (~200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less

Nonviral Vectors for Gene Delivery

Any design of nanoparticle vectors for cancer therapy or imaging must take into account the interaction of the nanoparticles with the tumor microenvironment. Size, charge, and shape have been shown to dominate this interaction.[1, 2] In vivo probing of solid tumors with particles of different sizes simultaneously has thus far been challenging due to the limitations of available nano-sized probes.[3–5] Fluorescent dextrans and other macromolecule probes have been used in studies with intravital microscopy, but heterogeneities across samples has prevented their use for the simultaneous imaging of a size series of probes within the same tumour.[5] MRI contrast agents are another attractive set of probes due to the minimally-invasive nature of the technology,[6, 7] but the lower spatial resolution of MRI limits the imaging of heterogeneity within tumors, and the technique does not allow for simultaneous imaging and tracking of a size series of probes within the same tumor.

A Nanoparticle Size Series for In Vivo Fluorescence Imaging

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review

Cuminum cyminum and Carum carvi are the sources of cumin and caraway seeds respectively, which have been used since antiquity for the treatment of various indications in traditional healing systems in wide geographical areas. Cumin and caraway seeds are rich sources of essential oils and have been actively researched for their chemical composition and biological activities. In recent times (especially during the last 3 years) considerable progress has been made regarding validation of their acclaimed medicinal attributes by extensive experimental studies. In this attempt many novel bioactivities have been revealed. This review highlights the significance of cumin and caraway as potential source of diverse natural products and their medicinal applications.

https://e-lactancia.org/media/papers/CominoAlcaravea_Cuminum_cyminum_and_Carum_carvi-PharmRev2011.pdf

Cuminum cyminum and Carum carvi: An update.

Kaempferol, a potential cytostatic and cure for inflammatory disorders.

Diabetes mellitus (DM) is one of the leading causes of death in the word, especially in the developing countries like India. Hyperglycaemia in diabetes generates reactive oxygen species (ROS) and disturbs the endogenous antioxidant defence system that causes oxidative stress. Oxidative stress in turn generates several secondary complications in diabetic patients. Due to this, great interest has been developed towards the treatment of diabetes by controlling the oxidative stress with antioxidants. There are various synthetic antioxidants available in the market but are associated with many side effects. Thus, much of the interest is towards the screening of natural antioxidants from plant sources. Wheatgrass has a potent antioxidant efficacy and has been used as a health drink in everyday's life and is used to cure DM in folk medicine. Hence the present study is aimed to find the effect of wheatgrass on oxidative stress in diabetes. In our study either blood plasma or haemolysate and tissues (liver, heart, kidney and pancreas) were analysed to evaluate the levels of lipid peroxidative markers thiobarbutric acid reactive substances (TBARS) and lipid hydroperoxides (LH), enzymatic antioxidants; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and non enzymatic antioxidants; reduced glutathione (GSH) and vitamin C in male albino Wistar rats. The levels of TBARS and LH were significantly increased in diabetic rats, which were found to be reduced on treatment with wheatgrass. The levels of both enzymatic and non enzymatic antioxidants were decreased in diabetic rats, which were found to be reversed on treatment with wheatgrass. From this we conclude that wheatgrass has protective role on oxidative stress in diabetic rats.

PROTECTIVE ROLE OF WHEATGRASS ON OXIDATIVE STRESS IN STREPTOZOTOCIN INDUCED TYPE 2 DIABETIC RATS Research Article

Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC), induces 1% of all cancer deaths. Curcumin the active constituent of turmeric, is shown to be effective in the treatment of various cancers. In the present study, we explored the mechanistic role of bis-demethoxy curcumin analog (BDMC-A) as a chemotherapeutic agent. We investigated its inhibitory effect on invasion, angiogenesis, and metastasis in human laryngeal carcinoma (Hep-2) cells in comparison with curcumin. The effect of curcumin and BDMC-A on transcription factors (NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ, β-catenin, COX-2, MMP-9, VEGF, TIMP-2) involved in signal transduction cascade, invasion, and angiogenesis in Hep-2 cells were quantified using Western blotting and RT-PCR technique. ELISA was used to measure the pro-inflammatory markers in Hep-2 cells treated with curcumin and BDMC-A. The results showed that BDMC-A inhibits the transcription factors NF-κB, p65, c-Jun, c-Fos, STAT3, STAT5, PPAR-γ and β-catenin, which are responsible for tumor progression and malignancy. Moreover, BDMC-A treatment downregulated MMP-9, VEGF, TGF- β, IL-6 and IL-8 and upregulated TIMP-2 levels. The effects were more significant compared to curcumin. Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.

/pdf/synthetic-curcumin-analog-inhibiting-the-invasion-2gi6m1snab.pdf

Synthetic curcumin analog: inhibiting the invasion, angiogenesis, and metastasis in human laryngeal carcinoma cells via NF-kB pathway.

\n\nDrug resistance by the cancer cells towards current chemotherapeutic\napproaches poses a great challenge. In the present study, an indole analogue of a well-known plant\nderived anticancer molecule, curcumin, was tested for its Multidrug Resistance (MDR) reversing\npotential in induced multi drug resistant A549 cell line.\n\n\n\nHuman lung cancer cell line A549 was made Multidrug Resistant (MDR)\nby prolonged treatment with low dosage of Docetaxel, an established anticancer drug. The MDR\ninduction was confirmed by morphological evidence, Hoechst 33342 staining, MTT assay,\nRhodamine123 staining and RT-PCR of ABCB1 gene. Protein expression studies were carried out\nusing western blotting technique\n\n\n\nThe induced MDR A549 cells exhibited significant increase in the gene\nexpression of ABCB1 gene at the transcriptional level. Retention and efflux studies with Pglycoprotein\n(P-gp) substrate Rh123 indicated that indole curcumin inhibited P-gp mediated efflux\nof Rhodamine. Furthermore, treatment of MDR A549 cells with indole curcumin showed downregulation\nof gene expression of ABCB1 and COX 2. This was also confirmed from the decreased\nprotein expression of COX 2.\n\n\n\nThe results of the present study indicate that indole curcumin reverses multi drug\nresistance by downregulating the expression of ABCB1 and COX 2 genes. Thus, indole curcumin\nmay act as a potent modulator for ABCB1 and COX 2 mediated MDR in lung cancer.\n

Indole Curcumin Reverses Multidrug Resistance by Reducing the Expression of ABCB1 and COX2 in Induced Multidrug Resistant Human Lung Cancer Cells

Alcoholism is a broad term used for problems related to alcohol, medically considered as disease, specifically an addictive illness, abuse, and dependence. It is the major cause of liver disease in western countries. Alcoholic liver disease encompasses the hepatic alterations leading to fatty liver, hepatitis, and fibrosis or cirrhosis. Fried food items prepared with repeatedly heated polyunsaturated fatty acid (PUFA) exacerbate the disturbances induced by alcohol. The use of herbs to treat diseases is almost universal. Wheatgrass (WG) is used as a supplemental nutrition because of its unique curative properties. As it has antioxidant property, it prevents cancer, diabetes, and acts as liver cleanser. The present study was undertaken to evaluate the efficacy of WG on preserving membrane integrity in liver damage induced by alcohol and heated PUFA (ΔPUFA).The rats were divided into four groups. The animals in group 1 served as normal (standard diet), group 2 served as hepatotoxic (alcohol + ΔPUFA), group 3 served as treated (alcohol + ΔPUFA + WG), and group 4 served as WG control. The compositions of membrane fatty acid, total phospholipids, phospholipase A, C (PLA and PLC) were analyzed in liver to evaluate the effects of WG. Changes in fatty acid composition, decrease in phospholipids levels, and increase in PLA, PLC were observed in the diseased group. Restoration effect was seen in WG-treated rats. Histopathological observations were in correlation with the biochemical parameters. From the results obtained, we conclude that WG effectively protects the liver against alcohol and ΔPUFA-induced changes in fatty acid composition and preserves membrane integrity.

Rukkumani Rajagopalan

Papers

PROTECTIVE ROLE OF WHEATGRASS ON OXIDATIVE STRESS IN STREPTOZOTOCIN INDUCED TYPE 2 DIABETIC RATS Research Article

Synthetic curcumin analog: inhibiting the invasion, angiogenesis, and metastasis in human laryngeal carcinoma cells via NF-kB pathway.

Indole Curcumin Reverses Multidrug Resistance by Reducing the Expression of ABCB1 and COX2 in Induced Multidrug Resistant Human Lung Cancer Cells

Effect of Wheatgrass on Membrane Fatty Acid Composition During Hepatotoxicity Induced by Alcohol and Heated PUFA

A review on biomaterials-based scaffold: An emerging tool for bone tissue engineering