Reema Gabrani

Green tea extract: possible mechanism and antibacterial activity on skin pathogens.

Camellia sinensis (tea) is known for its therapeutic properties (anti-inflammatory, anti-microbial, anti-tumour, anti-oxidative and anti-ageing). Although, anti-microbial properties of green tea have been studied, its role against bacterial strains related to skin infections and mechanism of action is not well understood. We focussed on exploring anti-microbial activity and the basic mechanism of aqueous green tea leaf extract on selected bacterial strains. Staphylococcus epidermidis, Micrococcus luteus, Brevibacterium linens, Pseudomonas fluorescens and Bacillus subtilis were found to be sensitive to green tea extract via disc diffusion assay (zone of inhibition ≥7 mm). Minimal inhibitory concentration (MIC) was determined via nitro blue tetrazolium (NBT) assay (0.156-0.313 mg/ml). Moreover, the aqueous extract was found to be not toxic to the Vero cell-line up to a concentration of 500 μg/ml. The effect of aqueous extract on adhesion of different bacteria to Vero cells indicated that it inhibits the adhesion at its MIC value.

Recent patents on anti-telomerase cancer therapy.

Telomerase, a specialised RNA-directed DNA polymerase extends and stabilises the telomeres at the ends of the eukaryotic chromosomes. The progressive loss of telomeres results in limited number of cell divisions and has been linked to the mechanism of human cellular ageing. Tumour cells marked by indefinite proliferation have stable telomere length maintained by telomerase. The differential expression of the telomerase enzyme in normal and cancer cells have led to the evolution of tumour specific anti-telomerase approaches which inhibit the telomerase enzyme activity so as to destabilise and shorten the telomeres leading to senescence in cancer cells. In the current review, we have selected nine tumour specific anti-telomerase approaches based on their mechanism of action or the target components of the human telomerase enzyme: Antisense-oligonucleotides, hammerhead ribozymes, dominant negative hTERT, reverse-transcriptase inhibitors, immunotherapy, G-quadruplex stabilisers, gene therapy, small molecule inhibitors and RNA interference. Recent research developments for each of the anti-telomerase approaches with the detailed analysis of specific granted patents from the perspective of different claims and downstream applications have been provided. A comprehensive list of patents for the different anti-telomerase approaches which includes information regarding the authors and institutional ownership along with the year of issue of the patent has also been provided.

Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation

The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167–318 d·nm, PDI below 0.441, and −18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.

Escherichia coli biofilm: development and therapeutic strategies

Escherichia coli biofilm consists of a bacterial colony embedded in a matrix of extracellular polymeric substances (EPS) which protects the microbes from adverse environmental conditions and results in infection. Besides being the major causative agent for recurrent urinary tract infections, E. coli biofilm is also responsible for indwelling medical device‐related infectivity. The cell‐to‐cell communication within the biofilm occurs due to quorum sensors that can modulate the key biochemical players enabling the bacteria to proliferate and intensify the resultant infections. The diversity in structural components of biofilm gets compounded due to the development of antibiotic resistance, hampering its eradication. Conventionally used antimicrobial agents have a restricted range of cellular targets and limited efficacy on biofilms. This emphasizes the need to explore the alternate therapeuticals like anti‐adhesion compounds, phytochemicals, nanomaterials for effective drug delivery to restrict the growth of biofilm. The current review focuses on various aspects of E. coli biofilm development and the possible therapeutic approaches for prevention and treatment of biofilm‐related infections.

Combinatorial antimicrobial effect of curcumin with selected phytochemicals on Staphylococcus epidermidis

Staphylococcus epidermidis is reported to be the main causative agent of nosocomial infections. It has become increasingly difficult to treat this micro-organism because of the emergence of new antibiotic-resistant strains and its ability to form biofilm on medical associated devices. Phytochemicals acting in synergy are effective in killing the micro-organisms by lowering the doses, and synergistic compounds evade the development of resistance due to different mechanism of action. This study aims to determine the synergistic antimicrobial potential of curcumin with cinnamaldehyde, eugenol, and ellagic acid against S. epidermidis. Curcumin with ellagic acid as well as eugenol were found to have additive antimicrobial effect, whereas, in combination, curcumin and cinnamaldehyde were found to have synergistic effect against S. epidermidis (fractional inhibitory concentration index (FICI) = 0.5). Synergy between curcumin and cinnamaldehyde was established by time–kill kinetics and was further evaluated for antibiofilm activity. The dose required to inhibit biofilm formation was reduced to half than that needed to inhibit its planktonic culture (minimal inhibitory concentration (MIC) of curcumin = 3.12 μg/ml; MIC of cinnamaldehyde = 15.62 μg/ml; FICI = 0.248). Both curcumin and cinnamaldehyde disrupted the bacterial membrane for killing the bacteria as determined by permeability studies on Escherichia coli ML-35p.

Mapping interactions of Chikungunya virus nonstructural proteins.

The four nonstructural proteins (nsPs1-4) of Chikungunya virus (CHIKV) play important roles involving enzymatic activities and specific interactions with both viral and host components, during different stages of viral pathogenesis. Elucidation of the presence and/or absence of interactions among nsPs in a systematic manner is thus of scientific interest. In the current study, each pair-wise combination among the four nonstructural proteins of CHIKV was systematically analyzed for possible interactions. Six novel protein interactions were identified for CHIKV, using systems such as yeast two-hybrid, GST pull down and ELISA, three of which have not been previously reported for the genus Alphavirus. These interactions form a network of organized associations that suggest the spatial arrangement of nonstructural proteins in the late replicase complex. The study identified novel interactions as well as concurred with previously described associations in related alphaviruses.

Exploring Novel Approaches to Vaginal Drug Delivery

Vaginal route serves as a potential site of drug administration for local and systemic absorption of a variety of therapeutic agents. Despite being a non- invasive route of drug administration, the vagina has not been extensively explored as compared to other routes. Intravaginal drug delivery has been traditionally restricted to delivery of antinfectives to the local vaginal cavity. Concerted efforts have been made in the recent past to rediscover the vaginal route as a potential route for the delivery of therapeutically important molecules, proteins, peptides, small interfering RNAs, oligonucleotides, antigens, vaccines and hormones. The understanding of vaginal physiology has led to the design of specific intravaginal drug delivery systems to reach the systemic circulation. To overcome the limitations of conventional dosage forms administered through vaginal route various novel approaches like the use of mucoadhesive or bioadhesive polymers, pH- or temperature-sensitive polymers, liposomes, nanoemulsions, nanoparticles, vaginal inserts, multiple emulsions and hydrogels have been designed which enable controlled and prolonged release of drugs. The present article is a comprehensive review of the research and patents encompassing conventional dosage forms used for vaginal drug delivery with emphasis on newer platform technologies pertaining to intravaginal administration.

Intraviral Protein interactions of Chandipura Virus

Chandipura virus (CHPV) is an emerging rhabdovirus responsible for several outbreaks of fatal encephalitis among children in India. The characteristic structure of the virus is a result of extensive and specific interplay among its five encoded proteins. The revelation of interactions among CHPV proteins can help in gaining insight into viral architecture and pathogenesis. In the current study, we carried out comprehensive yeast two-hybrid (Y2H) analysis to elucidate intraviral protein-protein interactions. All of the interactions identified by Y2H were assessed for reliability by GST pull-down and ELISA. A total of eight interactions were identified among four viral proteins. Five of these interactions are being reported for the first time for CHPV. Among these, the glycoprotein (G)-nucleocapsid (N) interaction could be considered novel, as this has not been reported for any members of the family Rhabdoviridae. This study provides a framework within which the roles of the identified protein interactions can be explored further for understanding the biology of this virus at the molecular level.

Therapeutic effects of EGCG: a patent review.

ABSTRACT Introduction: Green tea contains polyphenolic flavanoids such as epigallocatechin-3- gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and epicatechin (EC). EGCG is the most abundant and active compound in green tea. Extensive research has shown that it has significant antioxidant, anti-carcinogenic, anti-microbial, and neuroprotective properties and has therapeutic potential against various human diseases. Areas covered: This review focuses on the applications of EGCG alone, and in combination with other compounds, for the treatment of various types of cancers, metabolic, neurodegenerative, and microbial diseases, and discusses its mechanism of action in cell line and animal modesl. Recent advances, which include the use of nanoencapsulated EGCG to enhance the drug delivery and reduce cell toxicity, have also been discussed along with the comprehensive analysis of the specific granted patents associated with EGCG. Expert opinion: Under the current scenario, the role of EGCG as a therapeutic agent is being utilised and new approaches are being formulated to overcome the problem of stability and bioavailability of EGCG. EGCG and its derivatives could be used for the development of drugs for the treatment of cancer, as well as various microbial, metabolic, and neurodegenerative diseases.

Host–pathogen interactome analysis of Chikungunya virus envelope proteins E1 and E2

Abstract The envelope proteins of Chikungunya virus (CHIKV) are known to play crucial roles in viral infection and spread. Although the role of envelope proteins in viral infection has been studied, the cellular interactors of these proteins are still elusive. In the present study, the ectodomains of CHIKV envelope proteins (E1 and E2) have been used for a high throughput yeast two-hybrid (Y2H) screening to identify the interacting host protein partners. Following a comparative analysis between the viral–host protein interaction data generated from Y2H and computational approach, five host proteins interacting with E1 and three host proteins interacting with E2 common to both datasets were identified. These associations were further verified independently by pull down and protein interaction ELISA. The identified interactions shed light on the possible cellular machinery that CHIKV might be employing during viral entry, trafficking, and evasion of immune system.