Development of Ficus religiosa extract-loaded emulsion system for topical application: Characterization and stability evaluation

Purpose: To develop, optimize and characterize a topical (W/O) emulsion containing 4 % Ficus religiosa extract for cosmeceutical purposes. Methods: The ethanol extract of Ficus religiosa was obtained by Soxhlet method. Various formulations were developed using paraffin oil, emulsifier (Abil®-EM 90) and purified water at different proportions, and their physical stability was assessed under different stress conditions, to enable selection of the most stable formulation. The optimized formulation based on stability studies was chosen for evaluation of different physical properties, i.e., color, liquefaction, phase separation, centrifugation, pH, droplet size and rheology, under accelerated conditions for 12 weeks. Results: The optimized formulation (F4) contained ethanol extract (4.0 %), Abil®-EM 90 (3.5 %), paraffin oil (14.0 %) and purified water (78.5 %), and remained stable on centrifugation under all stress conditions. The pH of the formulation remained within the specified range for human skin pH i.e. 4.5 – 6.0, and droplet size of dispersed phase also persisted within the size range of macroemulsion (1 – 100 μm) throughout the study period. Rheological properties of the formulation showed shear thinning response, and flow index value less than 1 resulted in pseudoplastic flow of emulsion. Conclusion: These results suggest that the optimized emulsion system was stable and can serve as a good medium for topical delivery of various natural substances

Regulation of cytoplasmic polyadenylation can generate a bistable switch

<p>Abstract</p> <p>Background</p> <p>Translation efficiency of certain mRNAs can be regulated through a cytoplasmic polyadenylation process at the pre-initiation phase. A translational regulator controls the polyadenylation process and this regulation depends on its posttranslational modifications e.g., phosphorylation. The cytoplasmic polyadenylation binding protein (CPEB1) is one such translational regulator, which regulates the translation of some mRNAs by binding to the cytoplasmic polyadenylation element (CPE). The cytoplasmic polyadenylation process can be turned on or off by the phosphorylation or dephosphorylation state of CPEB1. A specific example could be the regulation of Calcium/Calmodulin-dependent protein kinase II (αCaMKII) translation through the phosphorylation/dephosphorylation cycle of CPEB1.</p> <p>Result</p> <p>Here, we show that CPEB1 mediated polyadenylation of αCaMKII mRNA can result in a bistable switching mechanism. The switch for regulating the polyadenylation is based on a two state model of αCaMKII and its interaction with CPEB1. Based on elementary biochemical kinetics a high dimensional system of non-linear ordinary differential equations can describe the dynamic characteristics of the polyadenylation loop. Here, we simplified this high-dimensional system into approximate lower dimension system that can provide the understanding of dynamics and fixed points of original system. These simplified equations can be used to develop analytical bifurcation diagrams without the use of complex numerical tracking algorithm, and can further give us intuition about the parameter dependence of bistability in this system.</p> <p>Conclusion</p> <p>This study provides a systematic method to simplify, approximate and analyze a translation/activation based positive feedback loop. This work shows how to extract low dimensional systems that can be used to obtain analytical solutions for the fixed points of the system and to describe the dynamics of the system. The methods used here have general applicability to the formulation and analysis of many molecular networks.</p

Maintenance of PKMζ-modulated synaptic efficacies despite protein turnover

How can synaptic efficacies be maintained despite the fast turnover of proteins at synapses? Partially, we know that the synthesis of new proteins is essential for the induction of the late, long-lasting phase of long-term potentiation (L-LTP). Recent experiments suggest that the concentration of protein kinase Mζ (PKMζ) is increased during L-LTP and that inhibiting the PKMζ activity during the maintenance phase can effectively reverse L-LTP. Experiments have also shown that phosphorylation is necessary for the activation of PKMζ. However, it is not clear what mechanism maintains the level and activity of PKMζ despite protein turnover and phosphatase activity. Using a mathematical modeling framework, I examine the hypothesis that the activity of PKMζ is sustained through a local switching mechanism. The model for the switching mechanism is motivated by several experimental observations: 1) PKMζ has two phosphorylation sites; one is mediated by another constitutively active kinase, Phosphoinositide-dependent kinase 1 PDK1 (T410) and is essential for its activity, and another is an autophosphorylation site, T560. 2) The phosphorylation of PKMζ increases its stability and the doubly phosphorylated PKMζ has a significantly longer lifetime than the unphosphorylated and singly phosphorylated states of PKMζ. 3) The doubly phosphorylated PKMζ also regulates the new synthesis of PKMζ through a translation feedback loop. The present study implemented a mass action model consistent with these observations. The results show that such a model can be bistable and that L-LTP induction produces an increase in the total amount of PKMζ at active synapses. The increase in PKMζ concentration was maintained through the regulation of new protein synthesis by PKMζ. The results also show that blocking the activity of PKMζ in a dose-dependent manner can effectively abolish the increase in the total amount of PKMζ, which is consistent with the effect that the PKMζ inhibitor zeta inhibitory peptide (ZIP) has experimentally demonstrated. The model is consistent with available experimental results regarding the phosphorylation levels of PKMζ and the temporal aspects of blocking experiments and produces a new prediction

Factors causing stress among Pakistani working women

Women are traditionally considered to be confined within the four walls of their houses in the developing countries. They are still unable to play an active role in the development of society. They are striving to make their identity as an integral part of the society. Being a member of conservative developing society, women are still facing many hindrances, causing stressful situation for them, which prohibits them to participate actively in the economic development. This paper attempts to explore the critical factors creating stress among Pakistani working women. Based on literature review, the key stressors were identified to be as work life balance, gender discrimination, peers’ behaviour, lack of promotional opportunities and sexual harassment. These factors were found to be creating physiological, behavioural and psychological problems. The target of this study was the women working in secretarial and administrative positions in Pakistani organisations. Regression analysis was conducted to find out the impact of these stressors on working women. The results revealed that sexual harassment, peers’ behaviour and lack of promotional opportunities were the most dominant stressors

Preventive Strategies against Human Papillomaviruses

Human papillomavirus (HPV) infection is among the most common viral infections of the reproductive tract. Out of more than 100 different types of HPV identified so far, only a few (termed as “high-risk” subtypes) are associated with cervical cancer. On the other hand, “low-risk” subtypes are associated with genital warts and other benign changes in cervical and oral mucosa. Majority of the HPV infections usually clear up without any intervention within a few months. However, a fraction of HPV infections, such as those with types 16 and 18, can become persistent which may lead to the development of anogenital or cervical cancers. HPV subtypes 16 and 18 together are responsible for approximately 70% of all cervical cancer cases, the fourth major cause of cancer-related deaths in women. In the absence of any specific treatment options, preventive measures are considered as cornerstone of strategies aimed at curbing the burden of this disease. This chapter presents a comprehensive review of strategies that can be employed to prevent and eradicate HPV infection. Minimizing the exposure to HPV risk factors such as unprotected sex, multiple sex partners, early age sex, and not being circumcised, can reduce the chances of getting HPV infection to a significant level. Mass screening programs have also been effective in HPV eradication. Nevertheless, immunization against HPV has proven to be the most promising strategy in fight against HPV. Virus-like particles based on bivalent, quadrivalent, and nonavalent anti-HPV vaccines have been licensed and are available in market under the trade names of Cervarix®, Gardasil®, and Gardasil9®, respectively. Various clinical trials and population-based studies have demonstrated high levels of efficacy for all the three vaccines in preventing type-specific malignancies

Microbicides for the Prevention of HPV, HIV-1, and HSV-2: Sexually Transmitted Viral Infections

Sexually transmitted diseases (STDs) can be transmitted through genital-genital, orogenital, or anogenital contacts and remain to be a public health concern worldwide. Approximately one million people around the world are believed to be newly infected with sexually transmitted infections (STIs) each day. Numerous causative agents including bacteria, viruses, protozoa, yeast, and fungi are responsible for STIs; however, viruses exhibit more serious risks, probabilities and outcomes of STDs than other organisms. The most lethal viral STIs are human immunodeficiency virus-1 (HIV), herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), and human papillomavirus (HPV), which are responsible for major sexually transmitted viral infections including AIDS, herpes simplex, and genital warts, respectively. Despite the fact that several prevention strategies such as vaccination, abstinence from sex, limiting sex partners, the use of condoms and a range of therapeutic drugs have drastically reduced the risk of contracting STIs, these three infections continue to spread at an alarming rate. The high incidence and lack of effective vaccine, instigated scientists to look for alternate, cheap, and efficient strategies for controlling these deadly viruses. Microbicide are relatively new approach that may be helpful in preventing STIs transmission when applied inside the genitals before intercourse. Like other interventions, microbicides are used as prophylactic measures against STIs. Therefore, an excellent safety and efficacy profile analysis is mandatory before their approval for human use. Although no safe and efficacious microbicide is yet available, many candidates including nonoxynol-9, Savvy, cellulose sulfate, Carraguard, VivaGel, tenofovir gel, and PRO 2000 have shown promising in vitro activity and many more are under development. However, very few of them have moved to large-scale phase III trials. This chapter aims to provide a brief overview of various microbicides along with their mechanism of actions and recent updates on safety and effectiveness trials