Bench Discoveries Research Articles

Therapeutic potential of liver X receptor beta in depression and anxiety

Liver X receptors (LXRs), particularly LXRβ, are emerging as crucial players in the translation of basic neuroscience to clinical psychiatry. These nuclear receptor transcription factors, initially known for their roles in cholesterol metabolism and inflammation, are now revealing promising connections between molecular mechanisms and psychiatric symptoms. This review highlights recent breakthroughs in understanding LXRβ's regulation and function in behaviors relevant to depression and anxiety, derived from studies using animal paradigms that capture specific features of these disorders. We explore how these preclinical findings are shaping our comprehension of mood-related behaviors at the molecular level and potentially paving the way for innovative therapeutic strategies. As a ligand-activated transcription factor, LXRβ represents a novel target for drug development, potentially bridging the gap between bench discoveries and bedside treatments for neuropsychiatric disorders. We discuss the challenges and opportunities in translating LXRβ research into clinical interventions, emphasizing the potential for personalized medicine approaches in psychiatry. This bench-to-bedside article underscores the importance of LXRβ research in advancing our understanding and treatment of complex mental health conditions, while acknowledging the nuanced interpretation required when extrapolating from animal studies to human disorders.

SKA3 targeted therapies in cancer precision surgery: bridging bench discoveries to clinical applications-review article.

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, we comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis and narrative summary. We also provided top 10 predicted drugs targeting SKA3. We proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.

Forgone, Not Forgotten: “DNA Fingerprinting,” Migration Control and Britain’s DNA Profiling Pilot Project

DNA profiling has become a culturally ubiquitous technology. Its use, whether in forensic investigations, genetic databases, biomedical research, international border-making, or popular genealogy, has been familiarized through political debates, media and cultural representations and commercialization. DNA profiling has also attracted considerable scholarly attention across this terrain. However, scant attention has been paid to the key role played by legal migration in driving DNA profiling’s initial translation from lab bench discovery to “truth machine” and identity token. Here, I discuss the first state-sponsored use of DNA profiling as a tool for establishing kinship relations among legal but racialized migrants on Britain’s borders in the mid-1980s. I argue that this early “experiment” conditioned the commercialization and future uses of the technology at and beyond border zones. Reinstating migration as the origin context for DNA profiling, and retracing the postcolonial routes by which it entered the biopolitical sphere, sheds light on the conjoined naturalization and racialization of genetic technologies of identity and identification, whether at or beyond national borders.

Biology, technology and a bit of serendipity: an interview with Shiva Malek.

Biology, technology and a bit of serendipity: an interview with Shiva Malek.

Limited Treatment Options for Diabetic Wounds: Barriers to Clinical Translation Despite Therapeutic Success in Murine Models.

Significance: Millions of people worldwide suffer from diabetes mellitus and its complications, including chronic diabetic wounds. To date, there are few widely successful clinical therapies specific to diabetic wounds beyond general wound care, despite the vast number of scientific discoveries in the pathogenesis of defective healing in diabetes. Recent Advances: In recent years, murine animal models of diabetes have enabled the investigation of many possible therapeutics for diabetic wound care. These include specific cell types, growth factors, cytokines, peptides, small molecules, plant extracts, microRNAs, extracellular vesicles, novel wound dressings, mechanical interventions, bioengineered materials, and more. Critical Issues: Despite many research discoveries, few have been translated from their success in murine models to clinical use in humans. This massive gap between bench discovery and bedside application begs the simple and critical question: what is still missing? The complexity and multiplicity of the diabetic wound makes it an immensely challenging therapeutic target, and this lopsided progress highlights the need for new methods to overcome the bench-to-bedside barrier. How can laboratory discoveries in animal models be effectively translated to novel clinical therapies for human patients? Future Directions: As research continues to decipher deficient healing in diabetes, new approaches and considerations are required to ensure that these discoveries can become translational, clinically usable therapies. Clinical progress requires the development of new, more accurate models of the human disease state, multifaceted investigations that address multiple critical components in wound repair, and more innovative research strategies that harness both the existing knowledge and the potential of new advances across disciplines.

Shaping Up Mitochondria in Diabetic Nephropathy.

Mitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.

Modeling Cardiac Disease Mechanisms Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Progress, Promises and Challenges.

Cardiovascular diseases (CVDs) are a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, CVDs still represent the leading cause of mortality and morbidity worldwide. The hallmarks of cardiac diseases include heart dysfunction and cardiomyocyte death, inflammation, fibrosis, scar tissue, hyperplasia, hypertrophy, and abnormal ventricular remodeling. The loss of cardiomyocytes is an irreversible process that leads to fibrosis and scar formation, which, in turn, induce heart failure with progressive and dramatic consequences. Both genetic and environmental factors pathologically contribute to the development of CVDs, but the precise causes that trigger cardiac diseases and their progression are still largely unknown. The lack of reliable human model systems for such diseases has hampered the unraveling of the underlying molecular mechanisms and cellular processes involved in heart diseases at their initial stage and during their progression. Over the past decade, significant scientific advances in the field of stem cell biology have literally revolutionized the study of human disease in vitro. Remarkably, the possibility to generate disease-relevant cell types from induced pluripotent stem cells (iPSCs) has developed into an unprecedented and powerful opportunity to achieve the long-standing ambition to investigate human diseases at a cellular level, uncovering their molecular mechanisms, and finally to translate bench discoveries into potential new therapeutic strategies. This review provides an update on previous and current research in the field of iPSC-driven cardiovascular disease modeling, with the aim of underlining the potential of stem-cell biology-based approaches in the elucidation of the pathophysiology of these life-threatening diseases.

Stem Cells: The Game Changers of Human Cardiac Disease Modelling and Regenerative Medicine.

A comprehensive understanding of the molecular basis and mechanisms underlying cardiac diseases is mandatory for the development of new and effective therapeutic strategies. The lack of appropriate in vitro cell models that faithfully mirror the human disease phenotypes has hampered the understanding of molecular insights responsible of heart injury and disease development. Over the past decade, important scientific advances have revolutionized the field of stem cell biology through the remarkable discovery of reprogramming somatic cells into induced pluripotent stem cells (iPSCs). These advances allowed to achieve the long-standing ambition of modelling human disease in a dish and, more interestingly, paved the way for unprecedented opportunities to translate bench discoveries into new therapies and to come closer to a real and effective stem cell-based medicine. The possibility to generate patient-specific iPSCs, together with the new advances in stem cell differentiation procedures and the availability of novel gene editing approaches and tissue engineering, has proven to be a powerful combination for the generation of phenotypically complex, pluripotent stem cell-based cellular disease models with potential use for early diagnosis, drug screening, and personalized therapy. This review will focus on recent progress and future outcome of iPSCs technology toward a customized medicine and new therapeutic options.

The Crown and the Scepter: Roles of the Protein Corona in Nanomedicine.

Engineering nanomaterials are increasingly considered promising and powerful biomedical tools or devices for imaging, drug delivery, and cancer therapies, but few nanomaterials have been tested in clinical trials. This wide gap between bench discoveries and clinical application is mainly due to the limited understanding of the biological identity of nanomaterials. When they are exposed to the human body, nanoparticles inevitably interact with bodily fluids and thereby adsorb hundreds of biomolecules. A "biomolecular corona" forms on the surface of nanomaterials and confers a new biological identity for NPs, which determines the following biological events: cellular uptake, immune response, biodistribution, clearance, and toxicity. A deep and thorough understanding of the biological effects triggered by the protein corona in vivo will speed up their translation to the clinic. To date, nearly all studies have attempted to characterize the components of protein coronas depending on different physiochemical properties of NPs. Herein, recent advances are reviewed in order to better understand the impact of the biological effects of the nanoparticle-corona on nanomedicine applications. The recent development of the impact of protein corona formation on the pharmacokinetics of nanomedicines is also highlighted. Finally, the challenges and opportunities of nanomedicine toward future clinical applications are discussed.

Neuropathic Pain models caused by damage to central or peripheral nervous system.

Neuropathic Pain (NP) is a painful condition which is a direct consequence of a lesion or disease affecting the somatosensory system with symptoms like allodynia, hyperalgesia. It has complex pathogenesis as it involves several molecular signaling pathways, thus numerous reliable animal models are crucial to understand the underlying mechanism of NP and formulate effective management therapy. Some models like spinal cord injury, chronic constriction injury, spinal nerve ligation, chemotherapy induced peripheral neuropathy, diabetes-induced NP and many more are discussed. This review contains an overview of the procedures followed to induce neuropathy and specific characteristics of that particular model. Some new techniques like spared nerve ligation, have omitted the limitation of methods not presently used where complete nerve damage occurs. Since animal models provide a window to experienced symptoms and physiology and impact the translation of bench discoveries to the bedside, the reporting, interpretation and comparison of these models is necessary because slight variation in procedure of model generation can drastically alter the results. The development of novel, but rational analgesic drugs to alleviate this intractable pain demands elucidation of molecular mechanisms of NP for which different types of animal models have been established.

Novel Therapies for Acute Myeloid Leukemia: Are We Finally Breaking the Deadlock?

Acute myeloid leukemia (AML) is one of the best studied malignancies, and significant progress has been made in understanding the clinical implications of its disease biology. Unfortunately, drug development has not kept pace, as the '7+3' induction regimen remains the standard of care for patients fit for intensive therapy 40 years after its first use. Temporal improvements in overall survival were mostly confined to younger patients and driven by improvements in supportive care and use of hematopoietic stem cell transplantation. Multiple forms of novel therapy are currently in clinical trials and are attempting to bring bench discoveries to the bedside to benefit patients. These novel therapies include improved chemotherapeutic agents, targeted molecular inhibitors, cell cycle regulators, pro-apoptotic agents, epigenetic modifiers, and metabolic therapies. Immunotherapies in the form of vaccines; naked, conjugated and bispecific monoclonal antibodies; cell-based therapy; and immune checkpoint inhibitors are also being evaluated in an effort to replicate the success seen in other malignancies. Herein, we review the scientific basis of these novel therapeutic approaches, summarize the currently available evidence, and look into the future of AML therapy by highlighting key clinical studies and the challenges the field continues to face.

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic.

Informatics for Precision Medicine and Healthcare.

The past decade has witnessed great advances in biomedical informatics. Biomedical informatics is an emerging field of healthcare that aims to translate the laboratory observation into clinical practice. Smart healthcare has also developed rapidly with ubiquitous sensor and communication technologies. It is able to capture the online patient-centric phenotypic variables, thus providing a rich information base for translational biomedical informatics. Biomedical informatics and smart healthcare represent two interrelated disciplines. On one hand, biomedical informatics translates the bench discoveries into bedside, and, on the other hand, it is reciprocally informed by clinical data generated from smart healthcare. In this chapter, we will introduce the major strategies and challenges in the application of biomedical informatics technology in precision medicine and healthcare. We highlight how the informatics technology will promote the precision medicine and therefore promise the improvement of healthcare.

13. Sea anemone toxins: from lab bench discovery to commercial drugs?

13. Sea anemone toxins: from lab bench discovery to commercial drugs?

Evaluation and the NIH Clinical and Translational Science Awards

Since 2006, a total of 61 Clinical and Translational Science Institutes (CTSAs) have been funded by the National Institutes of Health (NIH), with the aim of reducing translation time from a bench discovery to when it impacts patients. This special issue of Evaluation & the Health Professions focuses on evaluation within and across the large, complex system of the CTSA Program of NIH. Through insights gained by reading the articles in this special edition and the experience of the authors, a "top ten" list of lessons learned and insights gained is presented. The list outlines issues that face those who evaluate the influence of the CTSA Program, as they work to anticipate what will be needed for continuing success. Themes include (1) considering the needs of stakeholders, (2) the perspective of the evaluators, (3) the importance of service improvement, (4) the importance of teams and people, (5) costs and return on investments, (6) methodology considerations to evaluate the CTSA enterprise, (7) innovation in evaluation, (8) defining the transformation of research, (9) evaluating the long-term impact of the CTSAs on public health, and (10) contributing to science policy formulation and implementation. The establishment of the CTSA Program, with its mandated evaluation component, has not only influenced the infrastructure and nature of translational research but will continue to impact policy and management in science.

Library-based clinical and translational research support

There has been a shift in the workflow at academic biomedical research and clinical care centers to promote more efficient clinical and community implementation of bench discoveries. Strong financial support for this effort is provided by the Clinical and Translational Science Awards (CTSAs) from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), awarded to about sixty biomedical research institutions constituting the CTSA Consortium [1]. CTSAs offer an opportunity to speed the translation of bench discoveries to improved human health by transforming the

Developing MicroRNA Therapeutics

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.

A bridge to somewhere

A bridge to somewhere

Alzheimer's Disease Research: A COIN Study Using Co-authorship Network Analytics

Using bibliometric data from 269 Alzheimer investigators and the 167,142 researchers contained in their two-step collaboration network (i.e., co-authors and co-authors of co-authors), an eigen decomposition of the 13,254 unique Medical Subject Heading (MeSH) terms associated with the 43,736 papers authored by the Alzheimer researchers was performed. A correspondence-analysis-based transformation of the data produced a bench-to-bedside translational spectrum along which each of the original 269 Alzheimer investigators were placed. The spectrum was found to naturally divide into two partitions one of which housed basic scientists while the other grouped together clinical researchers. In addition to the semantic partitions, two main coauthor subgroups were isolated, and the authors who were most central to those co-author subgroups were analyzed for their ability to bridge the “translational divide” which separated researchers grouped in the “bench” (i.e. basic science) partition from those in the “bedside” (i.e., clinical investigation) partition. If a given research community can be partitioned into bench and bedside components, then the possibility exists to use such a dataset to identify people who might be best suited to attempt to bridge the “translational divide” which often exists between those researchers who make scientific breakthroughs in the lab and those clinical investigators capable of bringing the bench discoveries to the patients in the form of clinical trials.

Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG)

Progress in the development of rationally based therapies for Duchenne muscular dystrophy has been accelerated by encouraging multidisciplinary, multi-institutional collaboration between basic science and clinical investigators in the Cooperative International Research Group. We combined existing research efforts in pathophysiology by a gene expression profiling laboratory with the efforts of animal facilities capable of conducting high-throughput drug screening and toxicity testing to identify safe and effective drug compounds that target different parts of the pathophysiologic cascade in a genome-wide drug discovery approach. Simultaneously, we developed a clinical trial coordinating center and an international network of collaborating physicians and clinics where those drugs could be tested in large-scale clinical trials. We hope that by bringing together investigators at these facilities and providing the infrastructure to support their research, we can rapidly move new bench discoveries through animal model screening and into therapeutic testing in humans in a safe, timely and cost-effective setting.