Nanoparticle-Encapsulated Camptothecin: Epigenetic Modulation in DNA Repair Mechanisms in Colon Cancer Cells.

Molecular crosstalk between the cellular epigenome and genome converge as a synergistic driver of oncogenic transformations. Besides other pathways, epigenetic regulatory circuits exert their effect towards cancer progression through the induction of DNA repair deficiencies. We explored this mechanism using a camptothecin encapsulated in ß-cyclodextrin-EDTA-Fe3O4 nanoparticles (CPT-CEF)-treated HT29 cells model. We previously demonstrated that CPT-CEF treatment of HT29 cells effectively induces apoptosis and cell cycle arrest, stalling cancer progression. A comparative transcriptome analysis of CPT-CEF-treated versus untreated HT29 cells indicated that genes controlling mismatch repair, base excision repair, and homologues recombination were downregulated in these cancer cells. Our study demonstrated that treatment with CPT-CEF alleviated this repression. We observed that CPT-CEF exerts its effect by possibly affecting the DNA repair mechanism through epigenetic modulation involving genes of HMGB1, APEX1, and POLE3. Hence, we propose that CPT-CEF could be a DNA repair modulator that harnesses the cell's epigenomic plasticity to amend DNA repair deficiencies in cancer cells.

Mini Review: Wound healing potential of edible plants.

Wound healing is a natural intricate cascade process involving cellular, biochemical and molecular mechanism to restore the injured or wounded tissue. Malaysia's multi-ethnic social fabric is reflected in its different traditional folk cuisines with different nutritional important ingredients. Despite these differences, there are some commonly used pantry ingredients among Malaysians and these ingredients may possess some healing power for acute and chronic wounds. These essential nutritional ingredients are included Amla (Ribes uva-crispa), Cinnamon (Cinnamomun venum), Curry Leaves (Murraya koenigii), Coriander (Coriandrum sativum), Fenugreek (Trigonella foenum-graecum), Garlic (Allium indica), Onion (Allium cepa) and Tamarind (Tamarindus indica). This article provides a review of the remedies with confirmed wound healing activities from previous experiments conducted by various researchers. Most of the researchers have focused only on the preliminary studies through appropriate model; hence detailed investigations which including pharmacological and pre-clinical studies are needed to discover its molecular mechanisms. In this review article, we have discussed about the wound healing potential of few commonly used edible plants and their known mechanism.

Biomedical and Textile Applications of Alternanthera sessilis Leaf Extract Mediated Synthesis of Colloidal Silver Nanoparticle.

The aqueous extract of Alternanthera sessilis (As) acts as the precursors for the quick reduction of silver ions, which leads to the formation of silver nanoparticles. In the agar, well diffusion method of the Klebsiella pneumoniae shows the minimal inhibitory concentration of 12 mm against A. sessilis mediated silver nanoparticles (As-AgNPs) at 60 µg/mL concentration. Fabric treated with novel AS-AgNPs is tested against the K. pneumoniae and shows an inhibitory action of 12 mm with mixed cotton that determines the antimicrobial efficacy of the fabrics. Uv- visible spectrophotometer was performed, showing a surface plasmon resonance peak at 450 nm cm-1. FTIR shows the vibration and the infrared radiation at a specific wavelength of 500-4000 cm-1. The HR-TEM analysis showed the presence of black-white crystalline, spherical-shaped As-AgNPs embedded on the fabrics range of 15 nm-40 nm. In the scanning electron microscope, the presence of small ball-shaped As-AgNPs embedded on the fabrics at a voltage of 30 KV was found with a magnification of 578X. EDAX was performed in which the nanoparticles show a peak of 2.6-3.9 KeV, and it also reveals the presence of the composition, distribution, and elemental mapping of the nanoparticles. The cytotoxic activity of synthesized nanosilver was carried out against L929 cell lines, which show cell viability at a concentration of 2.5 µg mL-1. Cell proliferation assay shows no cytotoxicity against L929 cell lines for 24 h. In this study, the green synthesis of silver nanoparticles from A. sessilis appears to be a cheap, eco-friendly, and alternative approach for curing infectious ulcers on the floor of the stratum corneum. Nanotechnology conjoined with herbal therapeutics provides a promising solution for wound management.

Extraction, Purification, and Characterization of Polysaccharides of Araucaria heterophylla L and Prosopis chilensis L and Utilization of Polysaccharides in Nanocarrier Synthesis.

BACKGROUND: Plant gums consist of polysaccharides which can be used in the preparation of nanocarriers and provide a wide application in pharmaceutical applications including as drug delivery agents and the matrices for drug release. The objectives of the study were to collect plant gums from Araucaria heterophylla L and Prosopis chilensis L and to extract and characterize their polysaccharides. Then to utilize these plant gum-derived polysaccharides for the formulation of nanocarriers to use for drug loading and to examine their purpose in drug delivery in vitro. METHODS: Plant gum was collected, polysaccharide was extracted, purified, characterized using UV-Vis, FTIR, TGA and GCMS and subjected to various bioactive studies. The purified polysaccharide was used for making curcumin-loaded nanocarriers using STMP (sodium trimetaphosphate). Bioactivities were performed on the crude, purified and drug-loaded nanocarriers. These polysaccharide-based nanocarriers were characterized using UV-Vis spectrophotometer, FTIR, SEM, and AFM. Drug release kinetics were performed for the drug-loaded nanocarriers. RESULTS: The presence of glucose, xylose and sucrose was studied from the UV-Vis and GCMS analysis. Purified polysaccharides of both the plants showed antioxidant activity and also antibacterial activity against Bacillus sp. Purified polysaccharides were used for nanocarrier synthesis, where the size and shape of the nanocarriers were studied using SEM analysis and AFM analysis. The size of the drug-loaded nanocarriers was found to be around 200 nm. The curcumin-loaded nanocarriers were releasing curcumin slow and steady. CONCLUSION: The extracted pure polysaccharide of A. heterophylla and P. chilensis acted as good antioxidants and showed antibacterial activity against Bacillus sp. These polysaccharides were fabricated into curcumin-loaded nanocarriers whose size was below 200 nm. Both the drug-loaded nanocarriers synthesized using A. heterophylla and P. chilensis showed antibacterial activity with a steady drug release profile. Hence, these natural exudates can serve as biodegradable nanocarriers in drug delivery.

Genomic plasticity between human and mycobacterial DNA: A review.

Mycobacterium tuberculosis has a remarkable ability of long-term persistence despite vigorous host immunity and prolonged therapy. The bacteria persist in secure niches such as the mesenchymal stem cells in the bone marrow and reactivate the disease, leading to therapeutic failure. Many bacterial cells can remain latent within a diseased tissue so that their genetic material can be incorporated into the genetic material of the host tissue. This incorporated genetic material reproduces in a manner similar to that of cellular DNA. After the cell division, the incorporated gene is reproduced normally and distributed proportionately between the two progeny. This inherent adoption of long-term persistence and incorporating the bacterial genetic material into that of the host tissue remains and is considered imperative for microbial advancement and chemotherapeutic resistance; moreover, new evidence indicates that the bacteria might pass on genetic material to the host DNA sequence. Several studies focused on the survival mechanism of M. tuberculosis in the host immune system with the aim of helping the efforts to discover new drugs and vaccines against tuberculosis. This review explored the mechanisms through which this bacterium affects the expression of human genes. The first part of the review summarizes the current knowledge about the interactions between microbes and host microenvironment, with special reference to the M. tuberculosis neglected persistence in immune cells and stem cells. Then, we focused on how bacteria can affect human genes and their expression. Furthermore, we analyzed the literature base on the process of cell death during tuberculosis infection, giving particular emphasis to gene methylation as an inherited process in the neutralization of possibly injurious gene components in the genome. The final section discusses recent advances related to the M. tuberculosis interaction with host epigenetic circuitry.

A Low Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B Resistance Phenotype among Methicillin-Susceptible Staphylococcus aureus Isolated from Malaysian Patients and Healthy Individuals.

BACKGROUND: Antibiotic resistance among Staphylococcus aureus is of great concern worldwide. This resistance is further complicated by the ability of S. aureus to confer cross-resistance to other antibiotics due to the presence of resistance genes, such as erythromycin resistance methylase (erm) genes, which render the bacterium resistant to macrolide-lincosamide-streptogramin B (MLSB) antibiotics. Resistance to these antibiotics can lead to therapeutic failure, resulting in significant morbidity and mortality in patients with S. aureus infections. OBJECTIVES: This study was performed to examine the distribution of MLSB-resistant strains of methicillin-susceptible S. aureus (MSSA), which were obtained from hospitalized patients and normal healthy individuals (carriers) using phenotypic methods, such as the double-disk diffusion (D-test) and the genotypic method by polymerase chain reaction (PCR). METHODS: A total of 183 nonduplicative MSSA isolates obtained from hospitalized patients (133) and carriers (50) in our previous studies were randomly selected for the D-test. The guidelines of the Clinical and Laboratory Standards Institute (CLSI) were used for the interpretation of the results of this test. The detection of ermA, ermB, ermC and msrA genes by PCR was performed for isolates that had positive D-test results and that were resistant to erythromycin. RESULTS: Of the 183 MSSA isolates, 97.2% and 98.4% were highly susceptible to erythromycin and clindamycin, respectively. MSLB resistance was detected in four isolates (2.2%). Of the 133 MSSA isolated from hospitalized patients, only 3.0% (4/133) and 2.3% (3/133) exhibited resistance to erythromycin and clindamycin, respectively. With regard to the MLSB resistance phenotypes, only 1.6% and 0.6% exhibited inducible MLSB (iMLSB) and MS phenotypes, respectively. The ermC gene was detected in all three iMLSB phenotypes, and the msrA gene was detected in the MS phenotype. Surprisingly, all MSSA isolates (100%) from carriers exhibited extremely high susceptibility to both antibiotics. CONCLUSIONS: The prevalence rates of iMLSB MSSA isolates vary according to geographical locations and the local antibiotic policy. The low prevalence rate of iMLSB MSSA isolates could probably be related to the judicious use of antibiotics for treating S. aureus infections in our studied population. Nonetheless, continuous antibiotic surveillance is still necessary to control any emergence of resistance isolates so that targeted therapy and effective control can be implemented accordingly.