Effects of Ascorbic Acid and Copper Treatments on Metallothionein Gene Expression and Antioxidant Enzyme Activities in Helianthus annuus L. Exposed to Chromium Stress

Journal of Plant Growth Regulation - Heavy metal pollution, which is one of the most important environmental problems, has a significant effect on plant growth and development. Plants influence all...     

GC/MS Profiling,In Vitro and In Silico Pharmacological Screening and Principal Component Analysis of Essential Oils from Three Exotic and Two Endemic Plants from Mauritius

The chemical and pharmacological profiles of essential oils (EOs) hydrodistilled in yields of 0.03–0.77 % (w/w) from three exotic (Cinnamomum camphora, Petroselinum crispum, and Syzygium samarangense) and two endemic (Pittosporum senacia subsp. senacia and Syzygium coriaceum) medicinal plants were studied. GC-MS/GC-FID analysis of the EOs identified the most dominant components to be myristicin (40.3 %), myrcene (62.2 %), 1,8-cineole (54.0 %), β-pinene (21.3 %) and (E)-β-ocimene (24.4 %) in P. crispum, P. senacia and C. camphora, S. samarangense and S. coriaceum EOs, respectively. All EOs were found to possess anti-amylase (0.70–1.50 mM ACAE/g EO) and anti-tyrosinase (109.35–158.23 mg KAE/g) properties, whereas no glucosidase inhibition was displayed. Only Syzygium EOs acted as dual inhibitors of both acetyl- and butyryl-cholinesterases, while P. senacia and C. camphora EOs inhibited acetylcholinesterase selectively and P. crispum EO was inactive (AChE: 4.64–4.96 mg GALAE/g; BChE: 5.96 and 7.10 mg GALAE/g). Molecular docking revealed 1,8-cineole to present the best binding affinities with butyrylcholinesterase, amylase and tyrosinase, while both myristicin and β-pinene with acetylcholinesterase and finally β-pinene with glucosidase. In vitro antioxidant potency was also demonstrated in different assays (DPPH: 13.52–53.91 mg TE/g, ABTS: 5.49–75.62 mg TE/g; CUPRAC: 45.38–243.21 mg TE/g, FRAP: 42.49–110.64 mg TE/g; and phosphomolybdenum assay: 82.61–160.93 mM TE/g). Principal component analysis revealed the EOs to differ greatly in their bioactivities due to their chemodiversity. This study has unveiled some interesting preliminary pharmacological profiles of the EOs that could be explored for their potential applications as phytotherapeutics.     

DNA repair XRCC1 Arg399Gln polymorphism is associated with the risk of development of end-stage renal disease

Patients with end-stage renal disease (ESRD) display enhanced genomic damage. DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in patients with ESRD and to evaluate their association with ESRD development. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we genotyped four single nucleotide polymorphisms (SNPs) in XPD codons 312 and 751 and XRCC1 codons 194 and 399 in 136 dialysis patients (71 patients undergoing hemodialysis and 65 subjected to peritoneal dialysis) and 147 healthy controls. Patients having XRCC1 399 Arg/Gln (OR:1.98; 95% CI: 1.21–3.25, P = 0.007) or XRCC1-399 Gln/Gln (OR: 3.95; 95% CI: 1.45–10.76, P = 0.005) genotype had a significantly higher risk of ESRD than those with XRCC1 399 Arg/Arg genotype. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls, with OR = 2.03 (95% CI = 1.08–3.81, P = 0.03). We further investigated the potential combined effect of these DNA repair variants on the risk of ESRD development. It was found that combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with the two possible genotypes of XPD-Asp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. This is the first report showing an association between DNA repair gene polymorphisms and ESRD development, and suggests that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of the disease. Further larger studies should be conducted to confirm these results.     

Web-based exchange of biochemical information

In this paper we present a web-based system for the semantic integration of biological data using a database model and an XML exchange format. The prototype developed integrates data related to enzymes.     

Novel Quinazolinone Derivatives: Potential Synthetic Analogs for the Treatment of Glaucoma,Alzheimer's Disease and Diabetes Mellitus

Quinazolinones, which represent an important part of nitrogen-containing six-membered heterocyclic compounds, are frequently used in drug design due to their wide biological activity properties. Therefore, the novel quinazolinones were synthesized from the reaction of acylated derivatives of 4-hydroxy benzaldehyde with 3-amino-2-alkylquinazolin-4(3H)-ones with good yields (85–94 %) and their structures were characterized using Fourier-transform Infrared (FT-IR), Nuclear Magnetic Resonance (¹H-NMR, ¹³C-NMR), and High-Resolution Mass Spectroscopy (HR-MS). As the application of the synthesized compounds, their inhibition properties of the synthesized compounds on α-Glucosidase (α-Glu), Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Carbonic anhydrase I–II (hCA I–II) metabolic enzymes were investigated. All compounds showed inhibition at nanomolar level with the K_i values in the range of 12.73±1.26–93.42±9.44 nM for AChE, 8.48±0.92–25.84±2.59 nM for BChE, 66.17±5.16–818.06±44.41 for α-Glu, 2.56±0.26–88.23±9.72 nM for hCA I, and 1.68±0.14–85.43±7.41 nM for hCA II. Molecular docking study was performed to understand the interactions of the most potent compounds with corresponding enzymes. Also, absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties of the compounds were investigated.     

Combination treatment optimization using a pan-cancer pathway model

The design of efficient combination therapies is a difficult key challenge in the treatment of complex diseases such as cancers. The large heterogeneity of cancers and the large number of available drugs renders exhaustive in vivo or even in vitro investigation of possible treatments impractical. In recent years, sophisticated mechanistic, ordinary differential equation-based pathways models that can predict treatment responses at a molecular level have been developed. However, surprisingly little effort has been put into leveraging these models to find novel therapies. In this paper we use for the first time, to our knowledge, a large-scale state-of-the-art pan-cancer signaling pathway model to identify candidates for novel combination therapies to treat individual cancer cell lines from various tissues (e.g., minimizing proliferation while keeping dosage low to avoid adverse side effects) and populations of heterogeneous cancer cell lines (e.g., minimizing the maximum or average proliferation across the cell lines while keeping dosage low). We also show how our method can be used to optimize the drug combinations used in sequential treatment plans—that is, optimized sequences of potentially different drug combinations—providing additional benefits. In order to solve the treatment optimization problems, we combine the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) algorithm with a significantly more scalable sampling scheme for truncated Gaussian distributions, based on a Hamiltonian Monte-Carlo method. These optimization techniques are independent of the signaling pathway model, and can thus be adapted to find treatment candidates for other complex diseases than cancers as well, as long as a suitable predictive model is available.     

Cytologic findings in pap smears with Actinomyces-like organisms

OBJECTIVE: To detect whether there is a relationship between the presence ofActinomyces-like organisms (ALOs) and cytologic findings. STUDY DESIGN: Papanicolaou-stained smears from 2290 women were examined cytologically. Nineteen (0.83%) of the 2290 were diagnosed with ALOs and became the study group. Patients without infectious agents (n=1792) were the control group. Statistical analyses were conducted with the chi2 test using the SPSS program (Chicago, Illinois, U.S.A.). RESULTS: The study and control groups were compared statistically. There was a significant correlation between the presence of ALOs and other cytologic findings, such as Trichomonas vaginalis, cocci, pseudoeosinophilia, endocervical cells, superficial cells, lactobacilli and polymorphonuclear leukocytes (p < 0.05), but there was no statistically significant difference between the presence of ALOs and metaplastic cells, parabasal cells or nuclear changes (p > 0. 05). CONCLUSION: ALOs in cervicovaginal smears might provide a milieu for growing some infectious agents, such as Trichomonas vaginalis and cocci. Lactobacilli were less plentiful in these cases. Vaginal discharge and abdominal pain were also important clinicalfindings for the detection ofALOs. Another finding was long-term usage of intrauterine contraceptive devices, which can cause the overgrowth of ALOs in vaginal mucosa.     

Relationship between the morphology of Candida cells and vaginal discharge

The aim of this study was to detect whether there is a correlation between the dimorphic pattern of Candida cells and various types of vaginal discharge. For this purpose, 2861 Papanicolaoustained cervicovaginal smears were examined cytologically and 265 of 2861 (9.26%) were diagnosed as having Candida cells. The 88 of 295 (29.83%) were identified as having blastospores only, 135 of 295 (45.76%) as having "hyphae only", and 47 of 295 (15.93%) as having both blastospores and hyphae of candida cells. There was a significant correlation between the type of candida cells and vaginal discharge (p < 0.05). The white-cheesy type vaginal discharge was the most prominent symptom for the observation the "hyphae only" following "blastospores only" and both blastospores and hyphae of Candida cells. It was suggested that hyphael form of Candida cells is the most pathogenic pattern and white-cheesy vaginal discharge is a marker for the presence of hyphael form in the vaginal mucosa.     

Engineering chromatin states: Chemical and synthetic biology approaches to investigate histone modification function

Patterns of histone post-translational modifications (PTMs) and DNA modifications establish a landscape of chromatin states with regulatory impact on gene expression, cell differentiation and development. These diverse modifications are read out by effector protein complexes, which ultimately determine their functional outcome by modulating the activity state of underlying genes. From genome-wide studies employing high-throughput ChIP-Seq methods as well as proteomic mass spectrometry studies, a large number of PTMs are known and their coexistence patterns and associations with genomic regions have been mapped in a large number of different cell types. Conversely, the molecular interplay between chromatin effector proteins and modified chromatin regions as well as their resulting biological output is less well understood on a molecular level. Within the last decade a host of chemical approaches has been developed with the goal to produce synthetic chromatin with a defined arrangement of PTMs. These methods now permit systematic functional studies of individual histone and DNA modifications, and additionally provide a discovery platform to identify further interacting nuclear proteins. Complementary chemical- and synthetic-biology methods have emerged to directly observe and modulate the modification landscape in living cells and to readily probe the effect of altered PTM patterns on biological processes. Herein, we review current methodologies allowing chemical and synthetic biological engineering of distinct chromatin states in vitro and in vivo with the aim of obtaining a molecular understanding of histone and DNA modification function. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.