Identifications small molecules inhibitor of p53-mortalin complex for cancer drug using virtual screening

Mortalin was over expressed in tumor cells and bind to p53 protein. This interaction was suggested to promote sequestration of p53 in the cytoplasm, thereby inhibiting its nuclear activity. The p53 is a tumor suppressor that is essential for the prevention of cancer development and loss of p53 function is one of the early events in immortalization of human cells. Therefore, abrogation p53-mortalin interaction using small molecule is guaranteed stop cancer cell grow. However study interaction of p53-mortalin, and its inhibition using small molecule is still challenging because specific site of mortalin that bind to p53, vice versa, is still debatable. This study has aims to analyze the p53-binding site of mortalin using molecular docking and to screen drug-like compounds that have potential as inhibitors of p53-mortalin interaction using virtual screening. The result showed that the lowest energy binding of p53-mortalin complex is -31.89 kcal/mol, and p53 protein bind to substrate binding domain of mortalin (THR433; VAL435; LEU436; LEU437; PRO442; ILE558; LYS555). Furthermore, the p53-binding domain of mortalin was used as receptor to screen 9000 drug-like compounds from ZINC database using molecular docking program Auto Dock Vina in PyRx 0.8 (Virtual Screening Tools). Here, we have identified three drug-like compounds that are ZINC01019934, ZINC00624418 and ZINC00664532 adequate to interrupt stability of p53-mortalin complex that warrant for anticancer agent

A hybrid feature selection on AIRS method for identifying breast cancer diseases

Breast cancer may cause a death due to the late diagnosis. A cheap and accurate tool for early detection of this disease is essential to prevent fatal incidence. In general, the cheap and less invasive method to diagnose the disease could be done by biopsy using fine needle aspirates from breast tissue. However, rapid and accurate identification of the cancer cell pattern from the cell biopsy is still challenging task. This diagnostic tool can be developed using machine learning as a classification problem. The performance of the classifier depends on the interrelationship between sample sizes, some features, and classifier complexity. Thus, the removal of some irrelevant features may increase classification accuracy. In this study, a new hybrid feature selection fast correlation based feature (FCBF) and information gain (IG) was used to select features on identifying breast cancer using AIRS algorithm. The results of 10 times the crossing (CF) of our validation on various AIRS seeds indicate that the proposed method can achieve the best performance with accuracy =0.9797 and AUC=0.9777 at k=6 and seed=50

A review on ethno-medicinal plants used in west Kalimantan

The purpose of the current study is to review ethno-medicinal plant used by natives in West Kalimantan Province in last five years. The methods used is gathering earlier publications in journals completed with pharmacological evidence of local medicinal plants. The present review result reported that 346 specieses belonging to 95 families have been utilized in West Kalimantan Province. Zingiberceae has the top number of plant of families (25) followed by Rubiaceae (17), Fabaceae (16), Asteraceae (14), Euphorbiaceae (13), Poaceae (13), Verbenaceae (13), Liliaceae (10), other families (<10).  The tabulated plant species in this study are frequently used as herbal medicine for the treatment of miscellaneous deseases and the medication safety of local people. Parts of plant used as herbal medicine are leaves (46.1%) followed roots (15.7%), fruits (9.5%), rhizomes (6.7%), all parts (5.9%), stems (5.4%), seeds (2.3%), saps (1.3%), pericarps (1.0%), flowers (0.8%), shoots (0.8%), stalks (0.8%), tubers (0.8%), and twigs (0.3%). The majorities of used methods for traditional medicine are decoction and infusion. The information of this current review includes local names, species, families, used parts, and medical uses. All the medicinal plants reported in this study have been used by West Kalimantan people for the treatment of various desease

Merger of Ayurveda and Tissue Culture-Based Functional Genomics: Inspirations from Systems Biology

Ayurveda is one of the ancient systems of health care of Indian origin. Roughly translated into "Knowledge of life", it is based on the use of natural herbs and herb products for therapeutic measures to boost physical, mental, social and spiritual harmony and improve quality of life. Although sheltered with long history and high trust, ayurveda principles have not entered laboratories and only a handful of studies have identified pure components and molecular pathways for its life-enhancing effects. In the post-genomic era, genome-wide functional screenings for targets for diseases is the most recent and practical approach. We illustrate here the merger of ayurveda and functional genomics in a systems biology scenario that reveals the pathway analysis of crude and active components and inspire ayurveda practice for health benefits, disease prevention and therapeutics

Epitope mapping of gp350/220 conserved domain of epstein barr virus to develop nasopharyngeal carcinoma (npc) vaccine

Nasopharyngeal carcinoma (NPC) is a malignant tumor in the nasopharyngeal epithelial cells that caused by many factors, one of which is the viral infection of EBV (Epstein Barr Virus). The standard treatments to cure NPC still have not been encouraging. The prevention through vaccination is an effective way to stop the disease. However, EBV vaccine being able to cover all variants of virus is still not available yet. Therefore, we identified the conserved region of glycoprotein 350/220 of EBV which has immunogenic and antigenic properties. The glycoprotein 350/220 is viral surface protein responsible to bind CR2 receptor, mediated EBV to enter the host cell. The conserved domain is crucial for EBV in infecting host cells. Further, by blocking CR2 binding domain of gp350/220 using antibody will inhibit EBV's spreading, and provoke an immune system to eliminate the virus in a patient. Glycoprotein 350/220 from all variants of Epstein-Barr virus was retrieved from NCBI. The conserved domain of gp350/220 was identified by aligning the protein sequences and structures. The polymorphic structure was used as a template for docking analysis to identify the resemblance of amino acid from polymorphic variants of gp350/220 that binds CR2. The epitope mapping of gp350/220 was done by Discotope BepiPred method. The result revealed that the conserved region of gp350/220 was predicted to have an epitope, QNPVYLIPETVPYIKWDNC residue, and it does not have any similarities to the human's cell surface protein. Therefore, it can be used as a reference to develop vaccine to prevent NPC

Alteration of Splicing Pattern on Angiotensin Converting Enzyme Gene Due To The Insertion of Alu elements

Angiotensin Converting Enzyme (ACE) is a zinc metallopeptidase that has a significant role in blood pressure regulation and the pathophysiology of hypertension. ACE has two protein domains, the N-domain and the C-domain, which each has a single active site that functions independently of each other. There is insertion/deletion by 288 bp Alu elements in the intron 16 of ACE gene. The Alu elements potentially alter splicing process. The effect of the insertion of Alu elements in the splicing pattern of the ACE gene has not been reported. Here, we report on the results of splicing pattern analysis of the ACE gene due to the insertion of Alu elements. Using an in-silico approach, we found the presence of Alu elements insertion in intron 16 of ACE caused alternative splicing and experienced exonization. Further analysis showed that the exonization lead to a premature termination codon (PTC), which is raised protein shortening and lost one of its two protein domains. The loss of one protein domain may affect the catalytic activity of ACE. These findings suggest that the Alu elements I/D polymorphism is related to the differences in the catalytic activity of ACE that may influence blood pressure regulation and hypertension

Assessment of bio-activities of the crude extract and components of Withania somnifera leaves by bioinformatics

Traditional herbal medicines are now increasingly being appreciated with Western models of integrative health sciences and evidence-based approach both in the basic research and clinic scenario. Ashwagandha is a commonly used plant in Ayurvedic, Indian traditional medicine. Medicinal value of Ashwagandha (WithaniasomniferaDunal) extends from anti-inflammatory, anti-arthritic, anti-rheumatic, rejuvenation and anti-cancer. Based on the belief that holistic multi-site mechanism of action offers greater chance of success, the traditional Ayurvedicmedicine practices the use of whole herb or its crude extract. It opposes with the mainstream of pharmaceutical industry that uses single and purified molecules. In the present study, we used bioinformatics approach to reveal the mechanism of action of (i) crude extract of Ashwagandha leaf extract and its purified components, (ii) Withanone and (iii) Withaferin A. Whereas p53-p21 was identified as a common signaling pathway for the three kinds of reagents, specific signaling pathways for Withaferin-A and Withanone were identified. Whereas the crude extract and Withanone were selectively toxic to human cancer cells, WithaferinA showed cytotoxicity to the normal cells too. The study suggested that the crude extract or a combinational formulamay be a superior and safenatural reagent for cancer treatment

Acid pH of saliva in dental caries of pre-school children repressed phagocytic capacity of neutrophil

In Indonesia dental caries is one of the most important issues in children’s health. Caries is one of common dental diseases in children who consume sugar-rich diets. Caries cause decalcification of tooth enamel and dentin. The bacteria involved in caries can converge on the dental pulp tissue and spread to other organs. Under adverse conditions, complications such as phylogenetic osteomyelitis and bacterial endocarditis can occur. This study aimed to investigate the effects of oral cavity pH on neutrophil and lymphocyte cell activity in order to eliminate S. mutans. Neutrophil and lymphocyte cells were isolated from the saliva of 30 preschool children, with and without caries, from the city of Surabaya, Indonesia. The dental condition was verified by a dentist based on the def-t index. Obtained results indicate that the number of activated neutrophils (CD11b+CD35+) from children in the caries group was significantly higher than the caries-free group at an acidic pH, but was unchanged at an alkaline pH. The activated neutrophils triggered naïve T cells to become effector T cells (CD4+), which produce cytokines to respond the infection. However, the increased CD11b+CD35+ were unable to enhance the phagocytic activity of neutrophils in the caries group, especially in acidic pH conditions. An acidic pH was found to repress the phagocytic capacity of neutrophils. This study provides a basis for future strategies to prevent dental caries by promoting phagocytic activity and maintaining a neutral pH in the oral cavity

Angiotensin-converting enzyme (ACE) I/D and bradykinin B2 receptor T/C genes polymorphism in patients with ACE inhibitors-related cough

Background: Angiotensin-converting enzyme (ACE) inhibitors-related cough had been reported to contribute for discontinuation of ACE inhibitors therapy. The role of ACE I/D and bradykinin B2 receptor T/C genes in ACE inhibitors-related cough is still unclear.Objectives: To determine ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in patients with ACE-inhibitors-related cough.Subjects and methods: An analytical study with cross-sectional design was conducted at Saiful Anwar General Hospital from June 2013 to September 2014. We used the polymerase chain reaction to genotype ACE I/D and bradykinin B2 receptor T/C genes. Data on both ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in cough and non cough group of hypertensive patients treated with ACE inhibitors in our Hospital during the period were analyzed using multiple logistic regression. Moreover, a metaanalysis was performed to summarize findings from other regions.Results: A total of 18 patients with cough (21%) and 67 patients without cough (79%) of hypertensive patients treated with ACE inhibitors from our Hospital during the period were analyzed for this study. In our population, no correlation was observed between ACE inhibitors-related cough and both ACE I/D (p = 0.560) and bradykinin B2 receptor T/C (p = 0.475) genes polymorphism. However, our meta-analysis of five studies consisting of 267 patients with cough and 346 patients without cough revealed that higher risk of ACE inhibitors-related cough was 1.82-fold associated with T allele of bradykinin B2 receptor T/C gene polymorphism (p = 0.0310).Conclusions: While the evidence in our meta-analysis suggests strong role for bradykinin gene polymorphism in ACE inhibitors-related cough, however, in our population, we did not find any association.Keywords: ACE inhibitors-related cough, ACE I/D gene polymorphism, Bradykinin B2 receptor T/C gene, polymorphism, Hypertensio