In silico analysis to contemplate the chemistry behind gallic acid-mediated inhibition of Polyketide Synthase A from aflatoxin biosynthesis pathway of Aspergillus flavus

Aspergillus flavus is known for producing the potent carcinogenic agent aflatoxin. Food contamination with aflatoxins is an important safety concern for agricultural yields. To identify and develop anti-aflatoxigenic agents, studies on phytochemicals as anti-aflatoxigenic agents have been documented including gallic acid. Thus, interaction studies using in-silico tools have been explored to understand the molecular mechanism behind inhibition of aflatoxin biosynthesis by studying the chemical interactions of gallic acid with polyketide synthase A (PksA) of A. flavus. The 3D structure of PksA consisting of seven domains was modeled using a Swiss-Model server followed by docking using Autodock tools-1.5.6 with substrate hexanoic acid and with that to gallic acid. The binding energy (electrostatic, inter-molecular or total internal energy) for gallic acid was lower (-6.09 to -4.79 kcal/mol) in comparison to hexanoic acid (-5.05 to -3.36 kcal/mol). During an interaction with the acyl transferase domain of PksA, both ligands showed H-bond formation at Glu36, Arg8, Thr11 positions. Ligplot analysis showed the formation of 7-H bonds in gallic acid and 3-H bonds in hexanoic acid. In addition, gallic acid showed stable binding with the active site of PksA indicated by steady root mean square deviation through molecular dynamic simulations. The chemistry between gallic acid and polyketide synthase A(PksA) exhibited that Gallic Acid possesses the highest level of binding potential (more number of hydrogen bonds) with PksA domain in comparison to hexanoic acid, a precursor for aflatoxin biosynthesis. Thus, we suggest enzymes from the aflatoxin biosynthetic pathway in aflatoxin-producing Aspergilli could be an important target for potential inhibitors.

Oncotherapeutic application of resveratrol-based inorganic nanoparticles

Background: Potential therapeutic benefits of natural phytoconstituents and the emergence of nano-structured drug delivery systems have expanded the scope of enhanced chemotherapy with minimal adverse effects. Various in vivo and in vitro studies have revealed Resveratrol to be a potent anti-carcinogenic agent. Researchers are ly applying the concept of nano-science for enhancing the delivery of phyto-drugs like resveratrol, in order to carry the drug to the affected tissues and organs of cancer patients with much ease and efficiency. Methods: The review emphasizes the use of inorganic nanoparticles for enhancing the delivery and efficacy of resveratrol into otherwise inaccessible tumorigenic tissues. Conclusion: The present review work summarizes a comprehensive update on the mechanism of actions of the resveratrol-based inorganic nanocomposite particles that are ly being studied against various cancer models. This work may be significant in laying the foundation for the future of metallic nanoparticles-based delivery and efficacy of phytochemicals in general and resveratrol in specific against non-invasive metastatic cancer.

Mekanisme Penuaan Kulit sebagai Dasar Pencegahan dan Pengobatan Kulit Menua

Seiring dengan meningkatnya populasi geriatri di Indonesia, masalah penuaan kulit juga turut meningkat. Pada populasi tersebut terjadi berbagai perubahan kulit sehingga kelainan yang ditimbulkan juga berbeda. Stres oksidatif merupakan mekanisme yang diduga kuat sebagai penyebab utama penuaan kulit. Penuaan kulit merupakan proses kompleks yang melibatkan faktor intrinsik dan ekstrinsik. Faktor intrinsik yang berperan adalah genetik, metabolisme sel, dan perubahan hormonal. Selain itu, terdapat faktor ekstrinsik seperti radiasi ultraviolet, inframerah, dan karsinogen lingkungan yang turut berperan pada penuaan kulit. Kedua faktor tersebut menyebabkan perubahan di seluruh lapisan kulit. Untuk mengatasi penuaan kulit, kini telah tersedia berbagai modalitas terapi, namun untuk menentukan terapi yang paling sesuai perlu diketahui fisiologi kulit menua, mekanisme penuaan kulit, dan manifestasi kelainan klinis kulit menua. Secara fisiologi terjadi perubahan permeabilitas, biokimia, vaskularisasi, termoregulasi, respons terhadap iritan, respons imunitas, kapasitas regenerasi, respons terhadap cedera, persepsi neurosensori dan pada tingkat genom. Jumlah sel epidermal dan laju pergantian epidermal menurun sedangkan di adneksa terjadi penurunan jumlah kelenjar sebasea yang mengakibatkan kulit kering dan mudah pecah. Penurunan jumlah melanosit menyebabkan warna rambut menjadi abu-abu keputihan dan muncul pigmentasi atipik di kulit. Folikel rambut kurang aktif sehingga meningkatkan kerontokan dan kebotakan. Di lapisan basal ukuran sel berkurang dan rerata ukuran sel bertambah. Sel keratinosit menjadi lebih pendek dan besar di kulit yang menua. Kata kunci: geriatri, mekanisme penuaan kulit, patofisiologi. Skin Aging Mechanism as A Basic Prevention and Treatment of Skin Aging Abstract Growing geriatric population generates a rise of aging issues. Process of aging develops multiple skin changes that further emerge other related skin problems. Oxidative stress is believed playing vital role related to aging. The aging process in the skin is complex and influenced by intrinsic and extrinsic factors. Intrinsic factors can be in the form of genetics, cell metabolism, and hormonal changes. Meanwhile, for extrinsic factors, such as exposure to ultraviolet, infrared, and carcinogenic agent also have crucial part in aging process. These factors contribute to all layers of the skin. Nowadays, many treatment modalities available to reverse skin aging, however, better understanding on skin aging mechanism, the pathophysiology, and clinical manifestations of aging skin is important to choose the appropriate treatment for patients. In aging, there are physiological changes in permeability, biochemical structures, vascularisation, thermoregulation, irritative response, immunity response, regenerative capability, inflammatory response, neurosensory perception and in genom level. The number of epidermal cells and epidermal overturn rate decline while there is also reduction of sebaseous glands at adnexa which both are accounted for skin xerosis. Decreasing melanocytes can caused gray hair and atypical pigmentation. Hair follicles also show less activity resulting in hair loss. Basal layer cells are downsizing and rise of average cells size are occured. Keratinocyte becomes shorter and bigger in aging skin. Keywords: geriatric, mechanism, skin aging, pathophysiology.

Transcriptomics and Cell Transformation Assay: an Integrated Approach to Evaluate the Effects of Low Dose Ionizing Radiation

Background and aims: Ionizing radiation (IR) are a well-known carcinogenic agent, acting through genotoxic mechanisms. In the last years, great attention has been paid to the effects of IR at low doses and to the non-monotonic dose-response curve for IR exposures. To improve the knowledge of IR-mediated effects and possibly identify biomarkers for IR effects, we combined the Cell Transformation Assay (CTA) with transcriptomics, to correlate cytotoxicity and transformation endpoints with the modulation of gene profiles after IR exposure. Methods: BALB/c3T3 cells were exposed to ionizing radiation ranging from 0.25Gy and 6Gy. Irradiated cells were seeded for the CTA 20h later. At the same time, RNA was extracted for microarray experiments. The cell clonal survival was significantly increased in 0.25Gy IR exposed cells, while the 3Gy dose strongly inhibited cellular growth. Cell transformation was observed only at the highest dose (3Gy). Results: Cell’s transformation was observed at 1.5, 2 and 3Gy doses. The 0.25Gy dose, which was able to induce an increment of clonal efficiency, did not induce cell transformation. The gene expression profile, which was obtained by comparing cells treated with the highest tested dose of 3Gy with the cells exposed to the lowest, not transforming, dose of 0.25Gy, identified several genes related to mitotic cell cycle and cholesterol biosynthesis. Conclusion: Our study showed that the up-regulation of genes belonging to the Spindle Assembly Checkpoint and mitosis progression could support the transforming ability of the 3Gy BALB/c3T3 exposed cells, probably through the involvement of genomic instability. Gene transcripts involved into cholesterol biosynthesis appear to be critical, as well. All these transcripts may be regarded as potential biomarkers of IR effects.

Exposure to acetaldehyde through food; a carcinogenic agent

The article's abstract is not available.

Protective Effects of Natural Products and Their Derivatives on Genetic Material: A Critical Review

Although treatment with natural products and the substances derived from them has gained much attention, it is important to know the genomic safety of these substances prior to their use in humans. The present review aims to present the current knowledge on the genoprotective effects and possible mechanism of actions of natural compounds. Therefore, an up-to-date search was conducted using known databases such as PubMed, ScienceDirect, and Clinicaltrials.gov. For the investigation of genotoxic/genoprotective activity of these substances, comet or micronucleus assay were frequently used models applied through eukaryotic test systems, bacterial strains, cultured animal cells or tissues (e.g., mice, rats) but also human by using oxidizing or carcinogenic agent-induced DNA damage capacity. Findings suggest that several extracts, including those from medicinal plants, marine algae or their preparations, antioxidants such as quercetin, retinoids, resveratrol, hyaluronic acid, carnosol, rosmarinic acid, and naringin have shown genoprotective effects in various test systems. Antioxidant, anti-inflammatory, mitogenic, reduction of DNA strand breaks and DNA lesions, formation of micronucleus, and chromosomal aberrations were the observed mechanisms of action of genoprotective substances. In conclusion, this review highlights the importance of natural products, especially dietary antioxidants, which can be safely used for the treatment of various diseases.

β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent.

Relation of h. pylori to gastric cancer

Introduction: Helicobacter Pylori (H. Pylori) is a gram negative bacterium spiraled in the gastric epithelium. This bacterium is responsible for triggering benign inflammatory processes and is considered a carcinogenic agent. Methodology: This is a bibliographic review based on the analysis of published works, evaluating the relationship between H.Pylori and the development of gastric cancer based on keywords indexed in the DECs (described in science and health): “Helicobacter Pylori” “Cancer” “Stomach” “Gastric cancer” and information from INCA (National Cancer Institute). Result and Discussions: Helicobacter Pyloriinfection is associated with gastric neoplasms in which adenocarcinomas are the most prevalent, with more than 90% of cases. The diagnosis is made through EDA (Upper Digestive Endoscopy) with biopsy of the lesions and has a sensitivity of 97%. The treatment of H. pylori in the patient diagnosed with gastric cancer depends on the type of neoplasia. Conclusion: The relationship between H.Pylori and neoplastic processes is evident. Therefore, proper diagnosis and treatment in all carriers of the bacterium is essential in order to reduce the risk of developing gastric cancer.

Toxicity and teratogenicity in zebrafish Danio rerio embryos exposed to chromium

Chromium (Cr) is an element present in nature in mineral form. It has a dual effect, both as an essential micronutrient and a carcinogenic agent depending on its chemical form and concentration. It is present in various environmental matrices such as water, soil, and air, coming from natural and anthropogenic sources, and causes harmful effects on biota, ecosystems, and even human beings. This study's objective was to evaluate chromium toxicity and teratogenicity in zebrafish embryos of Danio rerio exposed to chromium through the D. rerio teratology assay (DarTA) test by evaluating spine malformations. To this end, the chromium toxicity curve was calculated from zebrafish embryos exposed to potassium dichromate (K2Cr2O7), and the probit test was used to establish the mean lethal concentration (LC50) and three subtoxic concentrations LC25, LC12.5, and LC6.25 to evaluate the teratogenicity. The results showed that potassium dichromate was statistically positive for the teratogenic effect at the three highest concentrations evaluated. Potassium dichromate exposure causes abnormal embryonic development and teratogenic effects, including severe heart defects in zebrafish embryos. Therefore, we conclude that potassium dichromate is toxic to the zebrafish developmental stages. The finding that potassium dichromate is teratogenic in zebrafish embryos suggests that this metal should be tested and evaluate potential risk in mammalian systems.