ResearchPad - review https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Multifunctional magnetic iron oxide nanoparticles: an advanced platform for cancer theranostics]]> https://www.researchpad.co/article/elastic_article_14333 Multifunctional magnetic nanoparticles and derivative nanocomposites have aroused great concern for multimode imaging and cancer synergistic therapies in recent years. Among the rest, functional magnetic iron oxide nanoparticles (Fe3O4 NPs) have shown great potential as an advanced platform because of their inherent magnetic resonance imaging (MRI), biocatalytic activity (nanozyme), magnetic hyperthermia treatment (MHT), photo-responsive therapy and drug delivery for chemotherapy and gene therapy. Magnetic Fe3O4 NPs can be synthesized through several methods and easily surface modified with biocompatible materials or active targeting moieties. The MRI capacity could be appropriately modulated to induce response between T1 and T2 modes by controlling the size distribution of Fe3O4 NPs. Besides, small-size nanoparticles are also desired due to the enhanced permeation and retention (EPR) effect, thus the imaging and therapeutic efficiency of Fe3O4 NP-based platforms can be further improved. Here, we firstly retrospect the typical synthesis and surface modification methods of magnetic Fe3O4 NPs. Then, the latest biomedical application including responsive MRI, multimodal imaging, nanozyme, MHT, photo-responsive therapy and drug delivery, the mechanism of corresponding treatments and cooperation therapeutics of multifunctional Fe3O4 NPs are also be explained. Finally, we also outline a brief discussion and perspective on the possibility of further clinical translations of these multifunctional nanomaterials. This review would provide a comprehensive reference for readers to understand the multifunctional Fe3O4 NPs in cancer diagnosis and treatment.

]]>
<![CDATA[Emerging role of mTOR in tumor immune contexture: Impact on chemokine-related immune cells migration]]> https://www.researchpad.co/article/elastic_article_14325 During the last few decades, cell-based anti-tumor immunotherapy emerged and it has provided us with a large amount of knowledge. Upon chemokines recognition, immune cells undergo rapid trafficking and activation in disease milieu, with immune cells chemotaxis being accompanied by activation of diverse intercellular signal transduction pathways. The outcome of chemokines-mediated immune cells chemotaxis interacts with the cue of mammalian target of rapamycin (mTOR) in the tumor microenvironment (TME). Indeed, the mTOR cascade in immune cells involves migration and infiltration. In this review, we summarize the available mTOR-related chemokines, as well as the characterized upstream regulators and downstream targets in immune cells chemotaxis and assign potential underlying mechanisms in each evaluated chemokine. Specifically, we focus on the involvement of mTOR in chemokine-mediated immune related cells in the balance between tumor immunity and malignancy.

]]>
<![CDATA[Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities]]> https://www.researchpad.co/article/elastic_article_14307 Mesenchymal stem/stromal cells (MSCs) are important players in tissue homeostasis and regeneration owing to their immunomodulatory potential and release of trophic factors that promote healing. They have been increasingly used in clinical trials to treat multiple conditions associated with inflammation and tissue damage such as graft versus host disease, orthopedic injuries and cardiac and liver diseases. Recent evidence demonstrates that their beneficial effects are derived, at least in part, from their secretome. In particular, data from animal models and first-in-man studies indicate that MSC-derived extracellular vesicles (MSC-EVs) can exert similar therapeutic potential as their cells of origin. MSC-EVs are membranous structures loaded with proteins, lipids, carbohydrates and nucleic acids, which play an important role in cell-cell communication and may represent an attractive alternative for cell-based therapy. In this article we summarize recent advances in the use of MSC-EVs for tissue repair. We highlight several isolation and characterization approaches used to enrich MSC-derived EVs. We discuss our current understanding of the relative contribution of the MSC-EVs to the immunomodulatory and regenerative effects mediated by MSCs and MSC secretome. Finally we highlight the challenges and opportunities, which come with the potential use of MSC-EVs as cell free therapy for conditions that require tissue repair.

]]>
<![CDATA[Personalized neoantigen vaccination with synthetic long peptides: recent advances and future perspectives]]> https://www.researchpad.co/article/elastic_article_14295 Therapeutic cancer vaccines are one of the most promising strategies of immunotherapy. Traditional vaccines consisting of tumor-associated antigens have met with limited success. Recently, neoantigens derived from nonsynonymous mutations in tumor cells have emerged as alternatives that can improve tumor-specificity and reduce on-target off-tumor toxicity. Synthetic peptides are a common platform for neoantigen vaccines. It has been suggested that extending short peptides into long peptides can overcome immune tolerance and induce both CD4+ and CD8+ T cell responses. This review will introduce the history of long peptide-based neoantigen vaccines, discuss their advantages, summarize current preclinical and clinical developments, and propose future perspectives.

]]>
<![CDATA[Optimizing use of theranostic nanoparticles as a life-saving strategy for treating COVID-19 patients]]> https://www.researchpad.co/article/elastic_article_14282 On the 30th of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe.

In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells.

In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.

]]>
<![CDATA[Artificial sweeteners are related to non-alcoholic fatty liver disease: Microbiota dysbiosis as a novel potential mechanism]]> https://www.researchpad.co/article/elastic_article_14279 Non-alcoholic fatty liver disease (NAFLD) is a systemic and wide-spread disease characterized by accumulation of excess fat in the liver of people who drink little or no alcohol. Artificial sweeteners (ASs) or sugar substitutes are food additives that provide a sweet taste, and are also known as low-calorie or non-calorie sweeteners. Recently people consume increasingly more ASs to reduce their calorie intake. Gut microbiome is a complex ecosystem where 1014 microorganisms play several roles in host nutrition, bone mineralization, immune system regulation, xenobiotics metabolism, proliferation of intestinal cells, and protection against pathogens. A disruption in composition of the normal microbiota is known as ‘gut dysbiosis’ which may adversely affect body metabolism. It has recently been suggested that dysbiosis may contribute to the occurrence of NAFLD. The aim of the present study was to investigate the effects of ASs on the risk of NAFLD. The focus of this review is on microbiota changes and dysbiosis. Increasing evidence shows that ASs have a potential role in microbiota alteration and dysbiosis. We speculate that increased consumption of ASs can further raise the prevalence of NAFLD. However, further human studies are needed to determine this relationship definitively.

]]>
<![CDATA[Epigenetics and metabolism at the crossroads of stress-induced plasticity, stemness and therapeutic resistance in cancer]]> https://www.researchpad.co/article/elastic_article_14262 Despite the recent advances in the treatment of cancers, acquired drug resistance remains a major challenge in cancer management. While earlier studies suggest Darwinian factors driving acquired drug resistance, recent studies point to a more dynamic process involving phenotypic plasticity and tumor heterogeneity in the evolution of acquired drug resistance. Chronic stress after drug treatment induces intrinsic cellular reprogramming and cancer stemness through a slow-cycling persister state, which subsequently drives cancer progression. Both epigenetic and metabolic mechanisms play an important role in this dynamic process. In this review, we discuss how epigenetic and metabolic reprogramming leads to stress-induced phenotypic plasticity and acquired drug resistance, and how the two reprogramming mechanisms crosstalk with each other.

]]>
<![CDATA[Adaptive changes induced by noble-metal nanostructures <i>in vitro</i> and <i>in vivo</i>]]> https://www.researchpad.co/article/elastic_article_14213 The unique features of noble-metal nanostructures (NMNs) are leading to unprecedented expansion of research and exploration of their application in therapeutics, diagnostics and bioimaging fields. With the ever-growing applications of NMNs, both therapeutic and environmental NMNs are likely to be exposed to tissues and organs, requiring careful studies towards their biological effects in vitro and in vivo. Upon NMNs exposure, tissues and cells may undergo a series of adaptive changes both in morphology and function. At the cellular level, the accumulation of NMNs in various subcellular organelles including lysosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, and nucleus may interfere with their functions, causing changes in a variety of cellular functions, such as digestion, protein synthesis and secretion, energy metabolism, mitochondrial respiration, and proliferation. In animals, retention of NMNs in metabolic-, respiratory-, immune-related, and other organs can trigger significant physiological and pathological changes to these organs and influence their functions. Exploring how NMNs interact with tissues and cells and the underlying mechanisms are of vital importance for their future applications. Here, we illustrate the characteristics of NMNs-induced adaptive changes both in vitro and in vivo. Potential strategies in the design of NMNs are also discussed to take advantage of beneficial adaptive changes and avoid unfavorable changes for the proper implementation of these nanoplatforms.

]]>
<![CDATA[Endothelial cells produce angiocrine factors to regulate bone and cartilage via versatile mechanisms]]> https://www.researchpad.co/article/elastic_article_14192 Blood vessels are conduits distributed throughout the body, supporting tissue growth and homeostasis by the transport of cells, oxygen and nutrients. Endothelial cells (ECs) form the linings of the blood vessels, and together with pericytes, are essential for organ development and tissue homeostasis through producing paracrine signalling molecules, called angiocrine factors. In the skeletal system, ECs - derived angiocrine factors, combined with bone cells-released angiogenic factors, orchestrate intercellular crosstalk of the bone microenvironment, and the coupling of angiogenesis-to-osteogenesis. Whilst the involvement of angiogenic factors and the blood vessels of the skeleton is relatively well established, the impact of ECs -derived angiocrine factors on bone and cartilage homeostasis is gradually emerging. In this review, we survey ECs - derived angiocrine factors, which are released by endothelial cells of the local microenvironment and by distal organs, and act specifically as regulators of skeletal growth and homeostasis. These may potentially include angiocrine factors with osteogenic property, such as Hedgehog, Notch, WNT, bone morphogenetic protein (BMP), fibroblast growth factor (FGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF). Understanding the versatile mechanisms by which ECs-derived angiocrine factors orchestrate bone and cartilage homeostasis, and pathogenesis, is an important step towards the development of therapeutic potential for skeletal diseases.

]]>
<![CDATA[Neurohormones in the Pathophysiology of Vasovagal Syncope in Adults]]> https://www.researchpad.co/article/elastic_article_14185 Vasovagal syncope (VVS) is the most common cause of syncope across all age groups. Nonetheless, despite its clinical importance and considerable research effort over many years, the pathophysiology of VVS remains incompletely understood. In this regard, numerous studies have been undertaken in an attempt to improve insight into the evolution of VVS episodes and many of these studies have examined neurohormonal changes that occur during the progression of VVS events primarily using the head-up tilt table testing model. In this regard, the most consistent finding is a marked increase in epinephrine (Epi) spillover into the circulation beginning at an early stage as VVS evolves. Reported alterations of circulating norepinephrine (NE), on the other hand, have been more variable. Plasma concentrations of other vasoactive agents have been reported to exhibit more variable changes during a VVS event, and for the most part change somewhat later, but in some instances the changes are quite marked. The neurohormones that have drawn the most attention include arginine vasopressin [AVP], adrenomedullin, to a lesser extent brain and atrial natriuretic peptides (BNP, ANP), opioids, endothelin-1 (ET-1) and serotonin. However, whether some or all of these diverse agents contribute directly to VVS pathophysiology or are principally a compensatory response to an evolving hemodynamic crisis is as yet uncertain. The goal of this communication is to summarize key reported neurohumoral findings in VVS, and endeavor to ascertain how they may contribute to observed hemodynamic alterations during VVS.

]]>
<![CDATA[Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application]]> https://www.researchpad.co/article/elastic_article_14183 Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with high prevalence in the developed countries. NAFLD has been considered as one of the leading causes of cryptogenic cirrhosis and chronic liver disease. The individuals with obesity, insulin resistance and diabetes mellitus, hyperlipidaemia, and hypertension cardiovascular disease have a high risk to develop NAFLD. The related critical pathological events are associated with the development of NAFLD including insulin resistance, lipid metabolism dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. The development of NAFLD range from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis is characterized by fat accumulation, which represents the early stage of NAFLD. Then, inflammation triggered by steatosis drives early NAFLD progression into NASH. Therefore, the amelioration of steatosis and inflammation is essential for NAFLD therapy. The herbal medicine have taken great effects on the improvement of steatosis and inflammation for treating NAFLD. It has been found out that these effects involved the multiple mechanisms underlying lipid metabolism and inflammation. In this review, we pay particular attention on herbal medicine treatment and make summary about the research of herbal medicine, including herb formula, herb extract and naturals compound on NAFLD. We make details about their protective effects, the mechanism of action involved in the amelioration steatosis and inflammation for NAFLD therapy as well as the clinical application.

]]>
<![CDATA[Annexin A2 promotion of hepatocellular carcinoma tumorigenesis <i>via</i> the immune microenvironment]]> https://www.researchpad.co/article/elastic_article_14182 Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Annexin A2 (ANXA2), is found to promote cancer progression and therapeutic resistance. However, the underlining mechanisms of ANXA2 in immune escape of HCC remain poorly understood up to now. Herein, we summarized the molecular function of ANXA2 in HCC and its relationship with prognosis. Furthermore, we tentatively elucidated the underlying mechanism of ANXA2 immune escape of HCC by upregulating the proportion of regulatory T cells and the expression of several inhibitory molecules, and by downregulating the proportion of natural killer cells and dendritic cells and the expression of several inhibitory molecules or effector molecules. We expect a lot of in-depth studies to further reveal the underlying mechanism of ANXA2 in immune escape of HCC in the future.

]]>
<![CDATA[Targeting Mouse Double Minute 2: Current Concepts in DNA Damage Repair and Therapeutic Approaches in Cancer]]> https://www.researchpad.co/article/elastic_article_14158 Defects in DNA damage repair may cause genome instability and cancer development. The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair. The oncoprotein mouse double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. The major role of MDM2 is to inhibit p53 activity and promote its degradation. In this review, we describe the influence of MDM2 on genomic instability, the role of MDM2 on releasing p53 and binding DNA repair proteins to inhibit repair, and the regulation network of MDM2 including its transcriptional modifications, protein stability, and localization following DNA damage in genome integrity maintenance and in MDM2-p53 axis control. We also discuss p53-dependent and p53 independent oncogenic function of MDM2 and the outcomes of clinical trials that have been used with clinical inhibitors targeting p53-MDM2 to treat certain cancers.

]]>
<![CDATA[Potential Therapeutic Targets of B7 Family in Colorectal Cancer]]> https://www.researchpad.co/article/elastic_article_14137 Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway blockade has impressively benefited cancer patients with a wide spectrum of tumors. However, its efficacy in colorectal cancer (CRC) is modest, and only a small subset of patients benefits from approved checkpoint inhibitors. Newer checkpoints that target additional immunomodulatory pathways are becoming necessary to activate durable antitumor immune responses in patients with CRC. In this review, we evaluated the mRNA expression of all 10 reported B7 family members in human CRC by retrieving and analyzing the TCGA database and reviewed the current understanding of the top three B7 family checkpoint molecules (B7-H3, VISTA, and HHLA2) with the highest mRNA expression, introducing them as putative therapeutic targets in CRC.

]]>
<![CDATA[The Role of Lymphatic Vascular Function in Metabolic Disorders]]> https://www.researchpad.co/article/elastic_article_14133 In addition to its roles in the maintenance of interstitial fluid homeostasis and immunosurveillance, the lymphatic system has a critical role in regulating transport of dietary lipids to the blood circulation. Recent work within the past two decades has identified an important relationship between lymphatic dysfunction and patients with metabolic disorders, such as obesity and type 2 diabetes, in part characterized by abnormal lipid metabolism and transport. Utilization of several genetic mouse models, as well as non-genetic models of diet-induced obesity and metabolic syndrome, has demonstrated that abnormal lymphangiogenesis and poor collecting vessel function, characterized by impaired contractile ability and perturbed barrier integrity, underlie lymphatic dysfunction relating to obesity, diabetes, and metabolic syndrome. Despite the progress made by these models, the contribution of the lymphatic system to metabolic disorders remains understudied and new insights into molecular signaling mechanisms involved are continuously developing. Here, we review the current knowledge related to molecular mechanisms resulting in impaired lymphatic function within the context of obesity and diabetes. We discuss the role of inflammation, transcription factor signaling, vascular endothelial growth factor-mediated signaling, and nitric oxide signaling contributing to impaired lymphangiogenesis and perturbed lymphatic endothelial cell barrier integrity, valve function, and contractile ability in collecting vessels as well as their viability as therapeutic targets to correct lymphatic dysfunction and improve metabolic syndromes.

]]>
<![CDATA[Age-dependent root canal instrumentation techniques: a comprehensive narrative review]]> https://www.researchpad.co/article/elastic_article_14132 The aim of this article was to review age-dependent clinical recommendations for appropriate root canal instrumentation techniques. A comprehensive narrative review of canal morphology, the structural characteristics of dentin, and endodontic outcomes at different ages was undertaken instead of a systematic review. An electronic literature search was carried out, including the Medline (Ovid), PubMed, and Web of Science databases. The searches used controlled vocabulary and free-text terms, as follows: ‘age-related root canal treatment,’ ‘age-related instrumentation,’ ‘age-related chemo-mechanical preparation,’ ‘age-related endodontic clinical recommendations,’ ‘root canal instrumentation at different ages,’ ‘geriatric root canal treatment,’ and ‘pediatric root canal treatment.’ Due to the lack of literature with practical age-based clinical recommendations for an appropriate root canal instrumentation technique, a narrative review was conducted to suggest a clinical algorithm for choosing the most appropriate instrumentation technique during root canal treatment. Based on the evidence found through the narrative review, an age-related clinical algorithm for choosing appropriate instrumentation during root canal treatment was proposed. Age affects the morphology of the root canal system and the structural characteristics of dentin. The clinician’s awareness of root canal morphology and dentin characteristics can influence the choice of instruments for root canal treatment.

]]>
<![CDATA[Cytomegaloviruses and Macrophages—Friends and Foes From Early on?]]> https://www.researchpad.co/article/elastic_article_14126 Starting at birth, newborn infants are exposed to numerous microorganisms. Adaptation of the innate immune system to them is a delicate process, with potentially advantageous and harmful implications for health development. Cytomegaloviruses (CMVs) are highly adapted to their specific mammalian hosts, with which they share millions of years of co-evolution. Throughout the history of mankind, human CMV has infected most infants in the first months of life without overt implications for health. Thus, CMV infections are intertwined with normal immune development. Nonetheless, CMV has retained substantial pathogenicity following infection in utero or in situations of immunosuppression, leading to pathology in virtually any organ and particularly the central nervous system (CNS). CMVs enter the host through mucosal interfaces of the gastrointestinal and respiratory tract, where macrophages (MACs) are the most abundant immune cell type. Tissue MACs and their potential progenitors, monocytes, are established target cells of CMVs. Recently, several discoveries have revolutionized our understanding on the pre- and postnatal development and site-specific adaptation of tissue MACs. In this review, we explore experimental evidences and concepts on how CMV infections may impact on MAC development and activation as part of host-virus co-adaptation.

]]>
<![CDATA[Quality indicators in diagnostic upper gastrointestinal endoscopy]]> https://www.researchpad.co/article/elastic_article_14120 Upper gastrointestinal (UGI) endoscopy contributes a major clinical service with consistently growing demand around the world. Its utility corresponds to varying epidemiological issues throughout the globe, with cancer screening and surveillance being of the utmost priority. Despite high accuracy in neoplasia detection, UGI endoscopy remains a highly operator-dependent procedure, characterized by a substantial rate of missed pathology. Despite an overall lack of high-quality performance measures, there is an increased level of awareness about the need for quality control of this procedure, which is reflected in several guidelines and position statements published in recent years. It is widely recognized that quality assessment should go beyond mere technical aspects of the examination, and include both pre- and post-procedural factors. By this means, quality control encompasses the entire patient experience with the health care provider, from appropriate indication and physical assessment, through high-quality endoscopy service, to appropriate follow up and patient satisfaction. This article aims to review the available and emerging quality metrics for UGI endoscopy, taken mostly from Western endoscopy societies, with references to Asian recommendations where appropriate. The paper is limited solely to diagnostic UGI endoscopy and does not include performance measures for therapeutic procedures.

]]>
<![CDATA[Deciphering Natural Killer Cell Homeostasis]]> https://www.researchpad.co/article/elastic_article_14117 Natural killer (NK) cells have a central role within the innate immune system, eliminating virally infected, foreign and transformed cells through their natural cytotoxic capacity. Release of their cytotoxic granules is tightly controlled through the balance of a large repertoire of inhibitory and activating receptors, and it is the unique combination of these receptors expressed by individual cells that confers immense diversity both in phenotype and functionality. The diverse, yet unique, NK cell repertoire within an individual is surprisingly stable over time considering the constant renewal of these cells at steady state. Here we give an overview of NK cell differentiation and discuss metabolic requirements, intra-lineage plasticity and transcriptional reprogramming during IL-15-driven homeostatic proliferation. New insights into the regulation of NK cell differentiation and homeostasis could pave the way for the successful implementation of NK cell-based immunotherapy against cancer.

]]>
<![CDATA[Extreme Maternal Morbidity: a tracer event to improve the quality of obstetric care in Latin America]]> https://www.researchpad.co/article/elastic_article_14112 This article reviews critical aspects that have had an impact on the implementation of epidemiological surveillance of extreme maternal morbidity, as a tracer event of quality maternal care at population and institutional level; taking into account that maternal mortality has been usually monitored, and its analysis allows interventions to avoid maternal death. Until 2015, very few countries had been able to meet the goals established in the Millennium Development Goals (MDGs), especially MDG 5 - improving maternal health. As of today, it is observed that maternal mortality rate is quite heterogeneous, with rates from 1 case per 100,000 live births in developed countries, to more than 100 cases per 100,000 live births in developing countries. Therefore, complementary strategies such as surveillance of the extreme maternal morbidity could offer a more effective alternative to identify and implement interventions that allow us to prevent mortality and strengthen the quality of obstetric care. In addition, the importance of extreme maternal morbidity as a quality tracer event is that, unlike what is observed with maternal mortality, this is an event that occurs more frequently, is anticipatory of death, and the surviving pregnant woman is the primary source of information.

]]>