Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.

Tocotrienols, members of the vitamin E family, are natural compounds found in a number of vegetable oils, wheat germ, barley, and certain types of nuts and grains. Like tocopherols, tocotrienols are also of four types viz. alpha, beta, gamma and delta. Unlike tocopherols, tocotrienols are unsaturated and possess an isoprenoid side chain. Tocopherols are lipophilic in nature and are found in association with lipoproteins, fat deposits and cellular membranes and protect the polyunsaturated fatty acids from peroxidation reactions. The unsaturated chain of tocotrienol allows an efficient penetration into tissues that have saturated fatty layers such as the brain and liver. Recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol, δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of α-tocopherol against chronic diseases. These forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids and suppress proinflammatory signalling, such as NF-κB and STAT. The animal and human studies show tocotrienols may be useful against inflammation-associated diseases. Many of the functions of tocotrienols are related to its antioxidant properties and its varied effects are due to it behaving as a signalling molecule. Tocotrienols exhibit biological activities that are also exhibited by tocopherols, such as neuroprotective, anti-cancer, anti-inflammatory and cholesterol lowering properties. Hence, effort has been made to compile the different functions and properties of tocotrienols in experimental model systems and humans. This article constitutes an in-depth review of the pharmacology, metabolism, toxicology and biosafety aspects of tocotrienols. Tocotrienols are detectable at appreciable levels in the plasma after supplementations. However, there is inadequate data on the plasma concentrations of tocotrienols that are sufficient to demonstrate significant physiological effect and biodistribution studies show their accumulation in vital organs of the body. Considering the wide range of benefits that tocotrienols possesses against some common human ailments and having a promising potential, the experimental analysis accounts for about a small fraction of all vitamin E research. The current state of knowledge deserves further investigation into this lesser known form of vitamin E.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-7075-11-52) contains supplementary material, which is available to authorized users.

Healthcare is undergoing a rapid transformation from traditional hospital and specialist focused approach to a distributed patient-centric approach. Advances in several technologies fuel this rapid transformation of healthcare vertical. Among various technologies, communication technologies have enabled to deliver personalized and remote healthcare services. At present, healthcare widely uses the existing 4G network and other communication technologies for smart healthcare applications and are continually evolving to accommodate the needs of future intelligent healthcare applications. As the smart healthcare market expands the number of applications connecting to the network will generate data that will vary in size and formats. This will place complex demands on the network in terms of bandwidth, data rate, and latency, among other factors. As this smart healthcare market matures, the connectivity needs for a large number of devices and machines with sensor-based applications in hospitals will necessitate the need to implement Massive-Machine Type Communication. Further use cases such as remote surgeries and Tactile Internet will spur the need for Ultra Reliability and Low Latency Communications or Critical Machine Type Communication. The existing communication technologies are unable to fulfill the complex and dynamic need that is put on the communication networks by the diverse smart healthcare applications. Therefore, the emerging 5G network is expected to support smart healthcare applications, which can fulfill most of the requirements such as ultra-low latency, high bandwidth, ultra-high reliability, high density, and high energy efficiency. The future smart healthcare networks are expected to be a combination of the 5G and IoT devices which are expected to increase cellular coverage, network performance and address securityrelated concerns. This paper provides a state-of-the-art review of the 5G and IoT enabled smart healthcare, Taxonomy, research trends, challenges, and future research directions.INDEX TERMS 5G, smart healthcare, software-defined network, network function virtualization, the Internet of Things (IoT), device-to-device (D2D), ultra reliability and low latency communications.

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