The ubiquitin-proteasome pathway an emerging anticancer strategy for therapeutics: a patent analysis.

The degradation of intracellular proteins is targeted by ubiquitin via non-lysosomal proteolytic pathway in the cell system. These ubiquitin molecules have been found to be conserved from yeast to humans. Ubiquitin proteasome machinery utilises ATP and other mechanisms for degrading proteins of cytosol as well as nucleus. This process of ubiquitination is regulated by activating the E3 enzyme ligase, involved in phosphorylation. In humans, proteins which regulate the cell cycle are controlled by ubiquitin; therefore the ubiquitin-proteasome pathway can be targeted for novel anti-cancer strategies. Dysregulation of the components of the ubiquitin system has been linked to many diseases like cancer and inflammation. The primary triggering mechanism (apoptosis) of these diseases can also be induced when TNF-related apoptosis-inducing ligand (TRAIL) binds to its specific receptor DR4 and DR5. In this review, the emerging prospects and importance of ubiquitin proteasome pathway as an evolving anticancer strategy have been discussed. Current challenges in the field of drug discovery have also been discussed on the basis of recent patents on cancer diagnosis and therapeutics.

Application of risk-based assessment and management to riverbank filtration sites in India.

This is the first reported study of a riverbank filtration (RBF) scheme to be assessed following the Australian Guidelines for Managed Aquifer Recharge. A comprehensive staged approach to assess the risks from 12 hazards to human health and the environment has been undertaken. Highest risks from untreated ground and Ganga River water were identified with pathogens, turbidity, iron, manganese, total dissolved solids and total hardness. Recovered water meets the guideline values for inorganic chemicals and salinity but exceeds limits for thermotolerant coliforms frequently. A quantitative microbial risk assessment undertaken on the water recovered from the aquifer indicated that the residual risks of 0.00165 disability-adjusted life years (DALYs) posed by the reference bacteria Escherichia coli O157:H7 were below the national diarrhoeal incidence of 0.027 DALYs and meet the health target in this study of 0.005 DALYs per person per year, which corresponds to the World Health Organization (WHO) regional diarrhoeal incidence in South-East Asia. Monsoon season was a major contributor to the calculated burden of disease and final DALYs were strongly dependent on RBF and disinfection pathogen removal capabilities. Finally, a water safety plan was developed with potential risk management procedures to minimize residual risks related to pathogens.

Current developments in therapeutic and diagnostic strategies for Q fever: glimpses of patent analysis.

Coxiella burnetii is an infectious and etiological agent responsible for causing Q fever. There are mainly two forms of the Q fever that are chronic and acute. Though the acute type is usually linked with symptoms like pneumonia and hepatitis, the chronic form is shown to have mortality rate of 5%. Percentage of mortality rate might increases from 5% to 25% if left untreated. The present treatments of disease include the recommended dose of drugs and vaccine. Presently, extensive attempt is in progress to find novel therapies to combat the disease. This review is projected to provide a brief introduction of C. burnetii and Q fever while emphasizing therapeutics, prophylactic measures and diagnostic applications based on recent patents prospects.

Patent prospects toward therapeutics and diagnostics of anthrax.

Anthrax is one of the deadly infectious disease as documented in the CDC website. In spite of the availability of appropriate antimicrobial agents, the mortality related with the anthrax remains high. The pathogenicity of B. anthracis is mainly accredited to the two foremost components: toxins and capsule. Virulence component of B. anthracis includes protective antigen (PA) which plays a vital role in pathogenesis, virulence protein edema factor (EF) and lethal factor (LF). This search for novel therapeutic strategies that attack the proteins involved in the pathogenesis of anthrax and may potentially supplement antimicrobials being investigated. Currently, extensive attempts are in progress to develop novel helpful therapies to all of the virulence components: lethal factor, protective antigen, edema factor and the capsule of B. anthracis. This review discusses the potential anthrax therapeutic, prophylactic measures and diagnostic applications based on recent patents' prospects.

Current status of anti-tuberculosis therapy: a patent analysis.

Affecting more than one third of the world population, tuberculosis remains one of the world's most dreadful diseases, with no easy cures. Mycobacterial infestation and the evasion of host immune response are significantly responsible for the emergence of pulmonary tuberculosis. Mycobacterium tuberculosis, a weak gram positive, facultative aerobe colonizes in respiratory regions rich in oxygen reserves. Up regulation of CR and MR expression and function due to signaling by LAM results in electing immuno regulatory cytokines IL-4, IL-8 and Th2. Binding of NF-κB complex with mRNA prevention, due to mutation of leucine zipper domain of IK, inhibits the activation of cytokines and receptor molecules. Mechanism of energy generation by conversion of ADP to ATP, initiated by utilizing intermediary and/or end products of carbohydrate, amino acid or fatty acid catabolism is essential in approximating potential drug targets for elimination of the bacterium. A few improved diagnostic techniques have been evaluated over the last few years like Interferon Gamma Relese Assays, Nucleic Acid Amplification tests etc. of which most have certainly proven to facilitate specific detection of TB. Drugs like Rifampicin, Isoniazid etc. have also shown great curing effects on TB patients. Further research is required for better understanding of mechanism of pathogenesis and multiple drug resistance issues for developing the effective therapeutics and diagnostics against TB. The paper focuses on the effective diagnostics and therapeutics applications for tuberculosis prevention and cure based on recent patents and their analysis.

MicroRNA therapeutics: the emerging anticancer strategies.

The genetic alterations and aberrant miRNA expression profiles have been identified as important events behind the emergence of cancer. This knowledge triggers the use of miRNA therapeutics as an anticancer strategy. Basically, MicroRNAs (miRNAs) are approximately 22-nucleotide long, endogenous non-protein-coding RNA molecules which function as important regulatory molecules that regulate gene and protein expression through the RNA interference (RNAi) machinery. Transcription of these molecules by RNA polymerases II and III, resulting in the generation of precursor microRNAs that undergo a series of cleavage events, consequently, generate the mature microRNA. The biogenesis pathway is mediated by the two important cleavage events such as nuclear and cytoplasmic. The regulatory functions of microRNAs are accomplished through the RNA-induced silencing complex (RISC), leading to translational repression and hence, regulate the gene expression. The current progress in the development of strategies for miRNA-based anticancer therapies is due to its involvement in cellular, developmental and biological processes including regulation in cancer cell and modulation by various cancer chemoprophylaxis agents. Although miRNA therapeutics have been found to suppress gene expression effectively as compared to anti-sense oligonucleotide strategies, but it is bound with some limitations viz. identification of tissue specific miRNA, biological instability, off-target effects and delivery in the cell system. Up to certain extent, these hurdles have been resolved by chemical modifications using cholesterol conjugation, morpholinos, cationic lipids and cationic nanoparticles. Still more research is needed to understand the mechanism of action for better miRNA therapeutics. The paper discusses the potential miRNA therapeutics and diagnostic applications for cancer prevention, based on recent patents and their analysis.

Elucidating the interacting domains of chandipura virus nucleocapsid protein.

The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in viral life cycle, besides being an important structural component of the virion through proper organization of its interactions with other viral proteins. In a recent study, the authors had mapped the associations among CHPV proteins and shown that N protein interacts with four of the viral proteins: N, phosphoprotein (P), matrix protein (M), and glycoprotein (G). The present study aimed to distinguish the regions of CHPV N protein responsible for its interactions with other viral proteins. In this direction, we have generated the structure of CHPV N protein by homology modeling using SWISS-MODEL workspace and Accelrys Discovery Studio client 2.55 and mapped the domains of N protein using PiSQRD. The interactions of N protein fragments with other proteins were determined by ZDOCK rigid-body docking method and validated by yeast two-hybrid and ELISA. The study revealed a unique binding site, comprising of amino acids 1-30 at the N terminus of the nucleocapsid protein (N1) that is instrumental in its interactions with N, P, M, and G proteins. It was also observed that N2 associates with N and G proteins while N3 interacts with N, P, and M proteins.

The Wnt pathway: emerging anticancer strategies.

The canonical Wnt cascade has emerged as a critical regulator of cancer cells. Activation of the Wnt signaling pathway has also been associated with stem cell, thus raising the possibility of its role in embryogenesis and in the proliferation of malignant cancer cells. Wnt pathway has been reported to be involved in normal physiological processes in adult animals and integrally associated with cancer cell growth and maintenance, thus has been harnessed to devise strategies for anticancer therapy. The presence or absence of some members in this pathway, such as ß-catenin, Axin or APC, has been found to involve in different types of tumors in human beings. Dysregulation of the canonical Wnt/ß-catenin signaling pathway, mostly by inactivating mutations of the APC tumor suppressor, or oncogenic mutations of ß-catenin, has been implicated in colorectal tumorigenesis. Further, elevated levels of ß-catenin protein, a hallmark of activated canonical Wnt pathway, have been significantly observed in common forms of human malignancies, indicating that activation of the Wnt pathway may play an important role in tumor development and hence could be a crucial consideration for drug development. The paper discusses the potential therapeutic and diagnostic strategies directing on Wnt pathways on the basis of recent patents and their analysis.