Chemical and toxicological studies on black crust formed over historical monuments as a probable health hazard.

Studies to date have mostly investigated environmental factors responsible for deterioration of historical monuments. Black crusts formed on historical monuments are considered as factor for deterioration of structures or as an indicator of environmental status of the surrounding area. Black crust formed on historical monuments has never been investigated as a health hazard. Herein, for the first time, we performed in vitro and in vivo toxicology studies of black crust formed on three culturally-rich historical monuments (Rang Ghar, Kareng Ghar, and Talatal Ghar) of the Indian subcontinent to test their toxicological effect. Black crust suspension in ultrapure water was found not to be considerably toxic to the cells upon direct short-term exposure. However, the sub-acute nasal exposure of the black crust suspension in Swiss albino mice produced lung-specific pathologies and mortality. Additionally, structural formation of the black crust along with the speciation of potentially hazardous elements (PHEs), polyaromatic hydrocarbon (PAHs), and other metals were investigated. Overall, these results indicate the potential of black crust deposited on historical monuments as health hazard owing to the atmospheric pollution of the surroundings. However, it may be noted that black crust and its components have very low possibility of health implication unless they are disturbed without proper care.

A high level of TGF-B1 promotes endometriosis development via cell migration, adhesiveness, colonization, and invasiveness†.

Endometriosis is a prevalent gynecological disorder that eventually gives rise to painful invasive lesions. Increased levels of transforming growth factor-beta 1 (TGF-B1) have been reported in endometriosis. However, details of the effects of high TGF-B1 on downstream signaling in ectopic endometrial tissue remain obscure. We induced endometriotic lesions in mice by surgical auto-transplantation of endometrial tissues to the peritoneal regions. We then treated endometriotic (ectopic and eutopic endometrial tissues) and nonendometriotic (only eutopic endometrial tissues) animal groups with either active TGF-B1 or PBS. Our results demonstrate that externally supplemented TGF-B1 increases the growth of ectopically implanted endometrial tissues in mice, possibly via SMAD2/3 activation and PTEN suppression. Adhesion molecules integrins (beta3 and beta8) and FAK were upregulated in the ectopic endometrial tissue when TGF-B1 was administered. Phosphorylated E-cadherin, N-cadherin, and vimentin were enhanced in the ectopic endometrial tissue in the presence of TGF-B1 in the mouse model, and correlated with epithelial-mesenchymal transition (EMT) in ovarian endometriotic cells of human origin. Furthermore, in response to TGF-B1, the expression of RHOGTPases (RAC1, RHOC, and RHOG) was increased in the human endometriotic cells (ovarian cyst derived cells from endometriosis patient) and tissues from the mouse model of endometriosis (ectopic endometrial tissue). TGF-B1 enhanced the migratory, invasive, and colonizing potential of human endometriotic cells. Therefore, we conclude that TGF-B1 potentiates the adhesion of ectopic endometrial cells/tissues in the peritoneal region by enhancing the integrin and FAK signaling axis, and also migration via cadherin-mediated EMT and RHOGTPase signaling cascades.

Triazole analog 1-(1-benzyl-5-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)-2-(4-bromophenylamino)-1-(4-chlorophenyl)ethanol induces reactive oxygen species and autophagy-dependent apoptosis in both in vitro and in vivo breast cancer models.

Autophagy is considered as an important cell death mechanism that closely interacts with other common cell death programs like apoptosis. Critical role of autophagy in cell death makes it a promising, yet challenging therapeutic target for cancer. We identified a series of 1,2,3-triazole analogs having significant breast cancer inhibition property. Therefore, we attempted to study whether autophagy and apoptosis were involved in the process of cancer cell inhibition. The lead molecule, 1-(1-benzyl-5-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)-2-(4-bromophenylamino)-1-(4-chlorophenyl)ethanol (T-12) induced significant cell cycle arrest, mitochondrial membrane depolarization, apoptosis and autophagy in MCF-7 and MDA-MB-231 cells. T-12 increased reactive oxygen species and its inhibition by N-acetyl-L-cysteine protected breast cancer cells from autophagy and apoptosis. Autophagy inhibitor, 3-methyladenine abolished T-12 induced apoptosis, mitochondrial membrane depolarization and reactive oxygen species generation. This suggested that T-12 induced autophagy facilitated cell death rather than cell survival. Pan-caspase inhibition did not abrogate T-12 induced autophagy, suggesting that autophagy precedes apoptosis. In addition, T-12 inhibited cell survival pathway signaling proteins, Akt, mTOR and Erk1/2. T-12 also induced significant regression of tumor with oral dose of as low as 10mg/kg bodyweight in rat mammary tumor model without any apparent toxicity. In presence of reactive oxygen species inhibitor (N-acetyl-L-cysteine) and autophagy inhibitor (chloroquine), T-12 induced tumor regression was significantly decreased. In conclusion, T-12 is a potent inducer of autophagy-dependent apoptosis in breast cancer cells both in vitro and in vivo and can serve as an important lead in development of new anti-tumor therapy.