Green Synthesis of Genistein-Fortified Zinc Ferrite Nanoparticles as a Potent Hepatic Cancer Inhibitor: Validation through Experimental and Computational Studies.

In hepatic cancer, precancerous nodules account for damage and inflammation in liver cells. Studies have proved that phyto-compounds based on biosynthetic metallic nanoparticles display superior action against hepatic tumors. This study targeted the synthesis of genistein-fortified zinc ferrite nanoparticles (GENP) trailed by anticancer activity assessment against diethylnitrosamine and N-acetyl-2-aminofluorene induced hepatic cancer. The process of nucleation was confirmed by UV/VIS spectrophotometry, X-ray beam diffraction, field-emission scanning electron microscopy, and FT-IR. An in vitro antioxidant assay illustrated that the leaves of Pterocarpus mildbraedii have strong tendency as a reductant and, in the nanoformulation synthesis, as a natural capping agent. A MTT assay confirmed that GENP have a strong selective cytotoxic potential against HepG2 cancer cells. In silico studies of genistein exemplified the binding tendency towards human matrix metalloproteinase comparative to the standard drug marimastat. An in vivo anticancer evaluation showed that GENP effectively inhibit the growth of hepatic cancer by interfering with hepatic and non-hepatic biochemical markers.

Detection of the Synthetic Cannabinoids AB-CHMINACA, ADB-CHMINACA, MDMB-CHMICA, and 5F-MDMB-PINACA in Biological Matrices: A Systematic Review.

New synthetic cannabinoids (SCs) are emerging rapidly and continuously. Biological matrices are key for their precise detection to link toxicity and symptoms to each compound and concentration and ascertain consumption trends. The objective of this study was to determine the best human biological matrices to detect the risk-assessed compounds provided by The European Monitoring Centre for Drugs and Drug Addiction: AB-CHMINACA, ADB-CHMNACA, MDMB-CHMICA, and 5F-MDMB-PINACA. We carried out a systematic review covering 2015 up to the present date, including original articles assessing detection in antemortem human biological matrices with detailed validation information of the technique. In oral fluid and blood, SC parent compounds were found in oral fluid and blood at low concentrations and usually with other substances; thus, the correlation between SCs concentrations and severity of symptoms could rarely be established. When hair is used as the biological matrix, there are difficulties in excluding passive contamination when evaluating chronic consumption. Detection of metabolites in urine is complex because it requires prior identification studies. LC-MS/MS assays were the most widely used approaches for the selective identification of SCs, although the lack of standard references and the need for revalidation with the continuous emergence of new SCs are limiting factors of this technique. A potential solution is high-resolution mass spectrometry screening, which allows for non-targeted detection and retrospective data interrogation.

Phthalate metabolites: Characterization, toxicities, global distribution, and exposure assessment.

Phthalates are plasticizers in various products and regarded as endocrine disruptors due to their anti-androgen effects. Environmental occurrence and toxicities of parent phthalates have been widely reported, while the current state of knowledge on their metabolites is rarely summarized. Based on the available literature, the present review mainly aims to 1) characterize the potential metabolites of phthalates (mPAEs) using the pharmacokinetics evidences acquired via animal or human models; 2) examine the molecular and cellular mechanism involved in toxicity for mPAEs; 3) investigate the exposure levels of mPAEs in different human specimens (e.g., urine, blood, seminal fluid, breast milk, amniotic fluid and others) across the globe; 4) discuss the models and related parameters for phthalate exposure assessment. We suggest there is subtle difference in toxic mechanisms for mPAEs compared to their parent phthalates due to their alternative chemical structures. Human monitoring studies performed in Asia, America and Europe have provided the population exposure baseline levels for typical phthalates in different regions. Urine is the preferred matrix than other specimens for phthalate exposure study. Among ten urinary mPAEs, the largest proportions of di-(2-ethylhexyl) phthalate (DEHP) metabolites (40%), monoethyl phthalate (mEP) (43%) and DEHP metabolites/mEP (both 29%) were observed in Asia, America and Europe respectively, and mono-5-carboxy-2-ethypentyl phthalate was the most abundant compounds among DEHP metabolites. Daily intakes of phthalates can be accurately calculated via urinary mPAEs if the proper exposure parameters were determined. Further work should focus on combining epidemiological and biological evidences to establish links between phthalates exposure and biological phenotypes. More accurate molar fractions (FUE) of the urinary excreted monoester related to the ingested diesters should be collected in epidemiological or pharmacokinetic studies for different population.

Characterization of the bacteriophages binding to human matrix molecules.

Recent literature has suggested a novel symbiotic relationship between bacteriophage and metazoan host that provides antimicrobial defense protecting mucosal surface by binding to host matrix mucin glycoproteins. Here, we isolated and studied different bacteriophages that specifically interact with human extracellular matrix molecules such as fibronectin, gelatin, heparin and demonstrated their potency for protection to host against microbial infections. We showed that subpopulations of bacteriophages that work against clinical isolates of Escherichia coli can bind to pure gelatin, fibronectin and heparin and reduced bacterial load in human colon cell line HT29. The bacteriophages were characterized with respect to their genome sizes, melting curve patterns and host tropism (cross-reactivity with different hosts). Since, the bacteriophages are non-toxic to the host and can effectively reduce bacterial load in HT29 cell line their therapeutic potency against bacterial infection could be explored.

Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells.

Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified. The inhibitory effects of SME on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression were assessed using western blotting, reverse transcription-quantitative polymerase chain reaction and zymography assays. MMP-9 upstream signal proteins, including mitogen-activated protein kinases and activator protein 1 (AP-1) were also investigated. Cell invasion was assessed using a matrigel invasion assay. The present study demonstrated the inhibitory effects of the SME ethanol solution on MMP-9 expression and cell invasion in TPA-treated MCF-7 breast cancer cells. SME suppressed TPA-induced MMP-9 expression and MCF-7 cell invasion by blocking the transcriptional activation of AP-1. SME may possess therapeutic potential for inhibiting breast cancer cell invasiveness.

Human umbilical cord derived matrix: A scaffold suitable for tissue engineering application.

BACKGROUND: Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. OBJECTIVE: We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. METHODS: An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. RESULTS: The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. CONCLUSION: We developed a new matrix derived from human source that can be further used in tissue engineering.

Design of a dual aptamer-based recognition strategy for human matrix metalloproteinase 9 protein by piezoelectric biosensors.

MMP-9, human matrix metalloproteinase 9, belongs to the family of zinc-dependent peptide-bond hydrolases and is involved in the degradation of the extracellular matrix (ECM). In clinics, it is well known that elevated MMP-9 serum levels are associated with cardiovascular dysfunctions, several aspects of the physiology and pathology of the central nervous system, neuropsychiatric disorders and degenerative diseases related to brain tumors, and excitotoxic/neuroinflammatory processes. Due to the large interest of diagnostics in this protein, efforts to set up sensitive methods to detect MMP-9 for early diagnosis of a number of metabolic alterations are rapidly increasing. In this panorama, biosensors could play a key role; therefore we explored for the first time the development of an aptamer-based piezoelectric biosensor for a sensitive, label free, and real time detection of MMP-9. The detecting strategy involved two different aptamers in a sandwich-like approach able to detect down to 100 pg mL(-1) (1.2 pM) of MMP-9 as detection limit in standard solution. As proof of principle, commercial serum was investigated in terms of possible interferents, their identification and role in MMP-9 detection. The estimated detection limit for MMP-9 is about 560 pg mL(-1) (6.8 pM) in untreated serum.