A novel crosstalk between calcium/calmodulin kinases II and IV regulates cell proliferation in myeloid leukemia cells

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Identification of a potent herbal molecule for the treatment of breast cancer

<p>Abstract</p> <p>Background</p> <p>Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.</p> <p>Methods</p> <p>To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER⁺)-MCF-7 and estrogen-receptor negative (ER^-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.</p> <p>Results</p> <p>PDBD inhibits cell viability of ER⁺and ER^-BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting the mechanism of action of PDBD on BCa, we found that PDBD inhibits Akt signaling and its downstream targets such as NF-κB activation, IAP proteins and Bcl-2 expression. On the other hand, activation of JNK/p38 MAPK-mediated pro-apoptotic signaling was observed in both ER⁺and ER^-BCa cells.</p> <p>Conclusion</p> <p>These findings suggest that PDBD may have wide therapeutic application in the treatment of BCa.</p

Matrix metalloproteinases (MMP-8, MMP-9) and the tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) in patients with fungal keratitis

Purpose: To study the infiltrating cells and quantify the levels of matrix metalloproteinases (MMP-8, MMP-9) and tissue inhibitor of metalloproteinases (TIMP-1, TIMP-2) in the cornea, tear, and serum of patients with fungal keratitis. Methods: Experimental study. Infected corneal tissue from 4 patients with fungal keratitis (group 1) scheduled to undergo therapeutic keratoplasty accounted for the histopathologic and cytospin smear analysis. Ten patients with fungal keratitis from group 2 served for the quantification of MMPs and TIMPs. Five patients with keratoconus undergoing penetrating keratoplasty and 5 cadaver corneas were chosen as controls for group 2. Corneal buttons obtained during keratoplasty, 15 to 20 &#956;L of tears collected using the capillary flow method, and 3 mL of blood was obtained from patients with fungal keratitis and patients with keratoconus. Corneal button sections from group 1 were stained with hematoxylin and eosin and Grocott methenamine silver nitrate for the histopathologic studies and Giemsa staining for the cytospin smear analysis. Enzyme-linked immunosorbent assay was used for the quantification of total MMP-8, MMP-9, TIMP-1, and TIMP-2 in the corneal homogenates, tear, and serum samples of group 2. Results: Corneal sections from group 1 revealed dense fungal filaments and a large proportion (91.4% &#177; 38%) of polymorphonuclear leukocytes (PMNs). Significant elevation in the levels of MMP-8 and MMP-9 (P &lt; 0.05) in the fungal keratitis corneas was observed in group 2 compared with the cadaver and keratoconus corneas. The ratio of MMP/TIMP was also higher in the fungal keratitis corneas. Conclusions: Infiltrating PMNs in the cornea of patients with fungal keratitis contributed to the increased activities of MMP-8 and MMP-9, thereby enhancing tissue destruction and derangement

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

Thymoquinone (TQ) is a bioactive component derived from the seeds of Nigella sativa that are commonly as black cumin. Evidences indicate that the medicinal properties of TQ have been recognized for more than 2000 years. TQ has been shown to possess potent chemopreventive properties that include anti-inflammatory and anti-neoplastic activities. Recent studies have unraveled the multiple mechanisms through which TQ exerts its chemopreventive and anticancer activity in different cancer cells in a contextual manner. The present review aims to provide a brief compendium on the molecular mechanisms through which TQ inhibits signaling pathways underlying cancer genesis, progression, and metastasis

Growth Factor erv1-like Modulates Drp1 to Preserve Mitochondrial Dynamics and Function in Mouse Embryonic Stem Cells

Gfer links mitochondrial dynamics with pluripotency in mouse embryonic stem cells through its modulation of the mitochondrial fission GTPase Drp1

Michael Addition Based Chemodosimeter for Serum Creatinine Detection Using (<i>E</i>)‑3-(Pyren-2-yl)-1-(3,4,5-tri­methoxy­phenyl)prop-2-en-1-one Chalcone

First, a simple and highly emissive fluorescent chalcone (<i>E</i>)-3-(pyren-2-yl)-1-(3,4,5-trimethoxy­phenyl)­prop-2-en-1-one (PTP) was synthesized via simple shaking along with an excellent quantum yield of 0.85, and proved as a stable, highly sensitive, and selective biosensor for creatinine. Owing to its unique photophysical interaction with creatinine through Michael adduct formation, PTP was utilized as a Chemodosimeter for the selective recognition of creatinine in blood serum. Under optimized conditions, a broad range of creatinine detection was achieved  from 0.00000113 mg/dL to 15.8 mg/dL along with an excellent limit of detection of 0.00000065 mg/dL (0.058 nM). This biosensor is highly reproducible even for different concentration levels of creatinine. It is the very first creatinine biosensor possessing a wider linear range for clinical applications for creatinine. To ensure its clinical application, blood serum samples of people of different age groups were collected from Alpha Hospital and analyzed for creatinine by using our chemodosimeter method and compared with data obtained using a commercial method in the Alpha hospital. Our data show very good agreement with clinical data. Because clinical protocol involves trienzymes and tedious sample preparation, no doubt, our chemodosimeter will be a cheap and sensitive option compared to the existing clinical methods