Molecular insights and novel approaches for targeting tumor metastasis.

In recent years, due to the effective drug delivery and preciseness of tumor sites or microenvironment, the targeted drug delivery approaches have gained ample attention for tumor metastasis therapy. The conventional treatment approaches for metastasis therapy have reported with immense adverse effects because they exhibited maximum probability of killing the carcinogenic cells along with healthy cells. The tumor vasculature, comprising of vasculogenic impressions and angiogenesis, greatly depends upon the growth and metastasis in the tumors. Therefore, various nanocarriers-based delivery approaches for targeting to tumor vasculature have been attempted as efficient and potential approaches for the treatment of tumor metastasis and the associated lesions. Furthermore, the targeted drug delivery approaches have found to be most apt way to overcome from all the limitations and adverse effects associated with the conventional therapies. In this review, various approaches for efficient targeting of pharmacologically active chemotherapeutics against tumor metastasis with the cohesive objectives of prognosis, tracking and therapy are summarized.

Potential anti-inflammatory and anti-apoptotic effect of Coccinia grandis plant extract in LPS stimulated-THP-1 cells.

Coccinia grandis (C. grandis) L is an Indian medicinal plant from the Cucurbitaceae family whose extracts possess anti-oxidant, anti-infective, and anti-inflammatory properties. The objective of the present study was to probe the potential immunomodulatory of C. grandis crude extract on different pathways in THP-1 cells as probed by changes in expression of several proteins. THP-1 cells were differentiated into macrophages after treatment with phorbol-12-myristate 13-acetate, followed by exposure to lipopolysaccharide (LPS) with or without 50 or 100 µg/ml of C. grandis extract. Treatment of the cells with the extract significantly downregulated the expression and release of pro-inflammatory cytokines (IL-6, IL-1ß, CCL2, CCL22, CXCL10/IP-10, CX3CL1 and CXCL8/IL-8), proteins (ERK5, BAX, BCL2, Cyclin D, ERK1, NF-κB, P-IκBα,P- NF-κB and P-p38) and molecular signaling pathways (NF-κB, p38 MAPK, ERK1/2 and IL-6/JAK/STAT3 signaling cascades). This study is the first to highlight the ability of C. grandis extract to modulate several pathways, including proliferation, the expression of inflammatory cytokines, phagocytosis, migration properties and apoptosis, in human monocytic THP-1 cells.

In Vitro Studies on the Immunomodulatory Effects of Pulicaria crispa Extract on Human THP-1 Monocytes.

BACKGROUND: Pulicaria crispa (P. crispa) is a plant from the Compositae family that exhibits antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities. OBJECTIVE: The current study aimed at investigating the immunomodulatory effects of P. crispa extract in lipopolysaccharide- (LPS-) stimulated human monocytic THP-1 cells. METHODS: To induce macrophage differentiation, THP-1 cell lines were treated with phorbol-12-myristate 13-acetate, followed by exposure to LPS with or without 50 or 100 µg/ml of P. crispa extract. The following tests were employed to test the immunomodulatory effects of the extract: MTT assay, ELISA, Western blotting analysis, cell migration and phagocytosis assays, and Annexin V staining method. RESULTS: Exposure to 100 µg/ml P. crispa extract significantly reduced THP-1 cell proliferation, migration, and phagocytosis (in LPS-stimulated cells, but not in unstimulated cells). Moreover, the extract alone significantly reduced the rate of THP-1 cell apoptosis, while it increased the rate of late apoptosis. Molecular investigations showed that treatment with P. crispa extract significantly upregulated the expression of ERK1, p-MAPK, P-P38, and Bcl2, while it significantly reduced the expression of ERK5, Bax, NF-κB, P-NF-κB, CCL1, CCL2, CCL5, CCL22, CXCL1, and CXCL10. CONCLUSION: Pulicaria crispa extract exhibited anti-inflammatory, antiproliferative, antimigratory, and antiphagocytic effects in LPS-stimulated THP-1 cells. Future studies should investigate these mechanisms in animal models with chronic inflammatory diseases.

Antimicrobial activity and molecular identification of Streptomyces strains isolated from Saudi Arabia.

Actinomycetes are group of Gram-positive bacteria with high GC-content in their DNA. They are extremely useful for the pharmaceutical industry due to their seemingly unlimited capacity to produce secondary metabolites with diverse biological activities and chemical structure. The genus Streptomyces constitutes 50% of the total population of soil actinomycetes and about 75% of commercially and medicinally useful antibiotics that have been derived from this genus. The present study aimed in isolation of bioactive compound showing antimicrobial activities from soil Streptomyces, previously isolated and morphologically characterized from Jazan in Saudi Arabia. Six potent Streptomyces strains: JS3, JS4, JS6, JD7, JA8 and JA10 were chosen for antimicrobial activity screening against 5 human pathogenic bacteria and 5 phytopathogenic fungi before molecular identification was done. For antibacterial activity, the results showed that inhibition zones were found to range between 3.25-26.875 mm diameters, while for antifungal activity, it ranged between 13.3-40 mm diameters. The entire sequence of the 16S rDNA was determined for the strains JS6, JD7, JA8 and JA10 and deposited in the GenBank. Future studies of actinomycetes isolated from the Kingdom of Saudi Arabia's soils will assist in the discovery of new compounds that would be of industrial, pharmaceutical and agricultural importance.