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Background: The development of cancer drugs is among the most focused “bench to bedside activities” to improve human health. Because of the amount of data publicly available to cancer research, drug development for cancers has significantly benefited from big data and Artificial Intelligence (AI). In the meantime, challenges, like curating the data of low quality, remain to be resolved. Objective: This review focused on the recent advancements in and challenges of AI in developing cancer drugs. Method: We discussed target validation, drug repositioning, de novo design, and compounds' synthetic strategies. Results and Conclusion: AI can be applied to all stages during drug development, and some excellent reviews detailing the applications of AI in specific stages are available.

Stroke is a major cause of mortality and morbidity worldwide. Effective treatments are limited. Molecular hydrogen is emerging as a novel medical gas with therapeutic potential for various neurological diseases, including stroke. We reviewed the experimental and clinical findings of the effects of molecular hydrogen therapy in stroke patients and models. The underlying neuroprotective mechanisms against stroke pathology were also discussed.

Atherosclerotic cardiovascular and cerebrovascular diseases are among the leading causes of morbidity and mortality worldwide. Given our recent understanding of its role as a small-molecule antioxidant and anti- inflammatory agent, hydrogen may play an important role in preventing and treating atherosclerotic cardiovascular and cerebrovascular disease. In the past decade, more than 50 publications in the English language literature considered the role of hydrogen as an anti-atherosclerotic agent. In this review, we summarized the pathophysiological characteristics and risk factors associated with atherosclerosis (AS) and the laboratory research data that focuses on hydrogen to prevent and treat this condition, including the responses observed in both animal models and human studies. We will also consider the molecular mechanisms underlying the efficacy of hydrogen molecules with respect to atherosclerotic disease. Future studies might include clinical trials with larger sample populations as well as experiments designed to explore the molecular mechanisms associated with hydrogen treatment in greater depth.

At present, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and global trends suggest that this panorama will persist or worsen in the near future. Thus, optimization of treatment strategies and the introduction of novel therapeutic alternatives for CVD represent key objectives in contemporary biomedical research. In recent years, phytotherapy-defined as the therapeutic use of whole or minimally modified plant components-has ignited large scientific interest, with a resurgence of abundant investigation on a wide array of medicinal herbs (MH) for CVD and other conditions. Numerous MH have been observed to intervene in the pathophysiology of CVD via a myriad of molecular mechanisms, including antiinflammatory, anti-oxidant, and other beneficial properties, which translate into the amelioration of three essential aspects of the pathogenesis of CVD: Dyslipidemia, atherosclerosis, and hypertension. Although the preclinical data in this scenario is very rich, the true clinical impact of MH and their purported mechanisms of action is less clear, as large-scale robust research in this regard is in relatively early stages and faces important methodological challenges. This review offers a comprehensive look at the most prominent preclinical and clinical evidence currently available concerning the use of MH in the treatment of CVD from a bench-to-bedside approach.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a natural protein expressed in a wide range of tissues in our body. It is a promising anti-cancer agent due to its selective killing of cancer cells, rendering normal cells unharmed. However, resistance occurs either intrinsically or develops over the course of TRAIL treatment. In view of its specificity to cancer cells, there is a pushing need to overcome TRAIL resistance. Curcumin (Cur), a natural active constituent of turmeric, has been evidenced to have anti-cancer properties. However, it is limited by its sparing solubility and low bioavailability. Combinational therapy is one of the most frequently used strategies to overcome these limitations, which has been proved to be more effective than monotherapy by achieving synergistic effects and reducing toxicity. This review aims to discuss TRAIL and its underlying apoptotic mechanisms, the combinational treatment of Cur and TRAIL in view of their respective limitations, and the underlying apoptotic mechanisms activated by the sensitization of cancers by Cur towards TRAIL-induced apoptosis. Finally, this review discusses the research gap and the author’s insight into this research area in bridging the research gap from bench to bedside.

The maintenance of health requires successful cell functioning, which in turn depends upon the proper and active conformation of proteins besides other biomolecules. However, occasionally these proteins may misfold and lead to the appearance and progression of protein conformational diseases. These diseases apart from others include several neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, and other lesser known diseases. Although much knowledge has been gained, these NDDs still warrant advance research in the elucidation of their mechanisms as well as effective therapeutic interventions and proper management. There is an ever-growing and urgent need to improve the diagnosis and management of NDDs due to their devastating nature, serious social impact and neuropsychiatric symptoms. It is also envisioned that we may be able to encourage, develop, and strengthen the cell defenses against amyloid toxicity and prevent neuronal destruction and consequently neurodegeneration. In this review, the implications of protein misfolding and aggregation in NDDs are discussed along with some of the most recent findings on the curative and beneficial effects of natural molecules such as polyphenols. This paper also reviews the anti-aggregation and protective effects of some organic and peptidic compounds duly supported experimentally, as prospective future therapeutics for NDDs. The synopses presented in this review shall prove helpful in further understanding of the causes, cures and management of lethal NDDs.

Peripheral artery disease (PAD) is a highly prevalent disease, which still has unmet medical needs. Therapeutic angiogenesis for PAD, achieved by gene therapy, has achieved promising results in preclinical studies and early-phase clinical trials, yet few late-phase clinical trials have been conducted or have not shown efficacy. This article provides an overview of the progression of angiogenesis research in gene therapy field as it applies to PAD. The focus of angiogenic growth factors and clinical trials is introduced as a frontier of therapeutic angiogenesis. The article also includes insights into future directions from bench to bedside.

With body composition it is possible to divide human body in compartments on the basis of different physical properties. The two level body composition model subdividing the whole body in fat mass and fat free mass is the most used in epidemiological and clinical studies in the elderly. Body composition techniques may be used to study ageing process. Changes in body composition occur as part of the normal ageing process and are associated with important effects on health and function. It has been shown that body composition changes with aging, with an increase in fat mass and a decrease in muscle mass, have important consequences on health and physical disability. Moreover body fat distribution changes with adverse metabolic profiles and increased cardiovascular risk. The purpose of this review is to describe the basic principles and techniques for fat free mass and fat mass evaluation, highlighting the advantages and limitations of different available body composition methods.

Adverse side effects or toxicities of a drug were previously regarded as a manifestation of drug's own characterizations, such as the chemical structure and property of a drug. More recently, increasing experimental or clinical data and modern ideas suggest that human's genetic factors also play indispensable roles in resulting neural side effects of a drug, especially in antidepressant-induced suicide and antibiotics-induced hearing loss. However, there are many questions and technological obstacles (including high costs and limited samples) in these kinds of researches and this makes genetic study of drug toxicities in its initial stage. In this review, we in depth address and analysis of this matter from some new perspectives and propose some new initiatives to improve this type of researches in future. It is also highly needed to expedite the translation of these pharmacogenetic concepts from bench to bedside.

Translational research is an emerging discipline that aims to fill the gap through the whole pipeline from bench to bedside. This review highlights the importance and urgency of incorporating translational research into the study of pharmacokinetic herb drug interactions (PHDI), based on an intensive discussion on the controversial and inconsistent reports from preclinical to clinical, in vitro to in vivo, and across different studies concerning PHDI. Current controversial and dispersed reports confer poor translational capacity of experimental research data to guiding the clinical practices. We propose that the herbal complexities in their chemical compositions, biphasic and tissue-specific effects of enzymes, and the present incomplete understanding of the disposition properties of herbal medicines themselves; and the enzymatic complexities in the species differences, individual genotype and phenotype, differential regulation during healthy and pathological conditions, substrate dependent modulations, and their interplay with transporters, collectively constitute the major translational blocks in PHDI from experimental research to daily clinical practice. In clinical considerations, this review indicates that PHDI are far from clear based on the isolated preclinical findings, and that the intestine is a much more susceptible site than liver when subjected to herbal regulations, and that enzymatic induction could be more predominant than inhibition upon chronic ingestion of herbal medicines. Hopefully, this review would be helpful for better understanding the nature of hurdles in PHDI research, and for igniting the future translational research initiatives.

Nanotechnology is an emerging branch of science for designing tools and devices of size 1 to 100 nm with specific function at the cellular, atomic and molecular levels. The concept of employing nanotechnology in biomedical research and clinical practice is best known as nanomedicine. Nanomedicine is an upcoming field that could potentially make a major impact to human health. Nanomaterials are increasingly used in diagnostics, imaging and targeted drug delivery. Nanotechnology will assist the integration of diagnostics/imaging with therapeutics and facilitates the development of personalized medicine, i.e. prescription of specific medications best suited for an individual. This review provides an integrated overview of application of nanotechnology based molecular diagnostics and drug delivery in the development of nanomedicine and ultimately personalized medicine. Finally, we identify critical gaps in our knowledge of nanoparticle toxicity and how these gaps need to be evaluated to enable nanotechnology to transit safely from bench to bedside.

The interaction between the brain and immune system has been intensely studied in patients with several central nervous system (CNS) disorders including brain trauma and brain tumours. Pioneering studies described cellular immune changes after human stroke more than three decades ago but the potential existence of a CNS- mediated immunodepression syndrome has obtained renewed attention only recently. The CNS and the immune system are extensively interconnected through neural pathways, hormonal cascades and cell-to-cell interactions orchestrated primarily by cytokines. Indeed, the balance between pro- and anti-inflammatory cytokines determines the prowess of the immunological response but could also influence the fate of the injured brain tissue and the threshold to develop complications including systemic infection. Prominent changes in primary and secondary lymphoid organs and increased susceptibility to infections and pneumonia have been described in a mouse model of transient focal cerebral ischemia in support of the existence of a stroke induced immunodepression syndrome. Yet, the intrinsic characteristics of secondary lymphoid organs located in areas that receive direct signals from the CNS could mediate anti-inflammatory responses after stroke. In human stroke, the balance between pro-inflammatory and anti-inflammatory cytokines is an important prognostic clinical factor. Recent data also suggest that the appearance infections early after stroke could be the manifestation of a stroke-induced immunodepression syndrome, characterized by strong adrenergic activity and excessive anti-inflammatory drive. Overall, current research suggests that a better understanding of the reciprocal effects between the CNS and the immune system could pave the way to more effective therapies for this devastating condition.